NIH Resources

ML Related Resources

NIH-RAID

http://grants.nih.gov/grants/guide/pa-files/PAR-09-027.html

The National Institutes of Health (NIH) Roadmap has established a pilot program called the NIH-RAID Pilot (Rapid Access to Interventional Development), similar to the National Cancer Institute’s (NCI) RAID program, to make available, on a competitive basis, certain critical resources needed for the development of new small molecule therapeutic agents. Services potentially available include: production, bulk supply, GMP manufacturing, formulation, development of an assay suitable for pharmacokinetic testing, and animal toxicology.

Synthesis in bulk of small molecules
Synthesis of oligonucleotides
Chemical synthesis of peptides
Scale-up production
Development of analytical methods
Isolation and purification of naturally occurring substances
Pharmacokinetic/ADME studies including bioanalytical method development
Development of suitable formulations
Manufacture of drug supplies
Range-finding initial toxicology
IND-directed toxicology
Product development planning and advice in IND preparation
Later-stage preclinical development of monoclonal antibodies, recombinant proteins, and gene therapy agents

Application process:

The NIH-RAID accepts applications three times per year (see Critical Dates )

Once an application is received, it is reviewed for responsiveness. After review, the applicants and Institutes and Centers (ICs) are provided with review scores and summaries. At this point an IC may decline an application or invite the applicant and his colleagues to present an investigator seminar on the project to allow the investigator to update the NIH on the status of the project, respond to inquiries, and discuss the plan for the future of the project. Cost assessments will be developed internally based upon the results of the discussion. Institutes will base their decision about co-sponsorship on the seminar (if applicable), the review score and summary, and their assessment of the need for public sector support in the topic area.

Semi-Custom Synthesis On-line Request System (SCSORS)

SCSORS serves as a means for NIH scientists to circulate requests for specific chemical samples among several thousand synthetic chemists and suppliers registered within the system. Sample quantities will range from milligram up to kilogram scale requests. Suppliers will be provided tools that allow them to review these requests and make proposals to NIH scientists for the synthesis of substances. Once fully implemented, SCSORS will become an archive of commercially accessible custom chemistry products for pharmaceutical research. It is expected that this database of commercially accessible substances will grow to over 250 million substances in the coming two years.

Application Process:
The SCSORS request process will initially be managed through a series of documents and email communications facilitated by ChemNavigator’s Procurement Services Group. The general application steps are as follows:

http://www.chemnavigator.com/gossl/register.asp

http://www.chemnavigator.com/cnc/services/iResearchSystemFastStart.pdf

Step 3 – Send ChemNavigator Your Custom Request (if necessary)

https://www.chemnavigator.com/members/login_screen.asp

PubChem

PubChem is a public database with annotated information about the biological activities of compounds in the Molecular Libraries Small Molecule Repository (MLSMR) as well as chemical structures and compound probe information.

PubChem was created on behalf of the Molecular Libraries Roadmap Initiative by the National Center for Biotechnology Information (NCBI). Various data, including records on substances and compounds and assay screening, are organized in three linked databases within the NCBI’s Entrez information retrieval system: PCSubstance, PCCompound, and PCBioAssay.

Links from PubChem’s chemical structure records to other Entrez databases provide information on biological properties. These include links to PubMed scientific literature and NCBI’s protein 3D structure resource. Links to depositor web sites provide further information on PubChem depositors. The databse also provides a fast chemical structure similarity search tool.

NIMH Psychoactive Drug Screening Program

This service provides screening of novel psychoactive compounds for pharmacological and functional activity at cloned human or rodent CNS receptors, channels, and transporters. Bryan Roth MD, PhD (University of North Carolina Chapel Hill) will perform pharmacological and functional screening of novel compounds as a contractor to NIMH.

Screening of compounds is provided to qualified academic investigators at no cost.

Assays for a large number of cloned human or rodent cDNAs for CNS receptors, channels and transporters. For a list of current receptors/transporters go to:clones.html
Ki determinations
Functional assays to determine effects on second messenger systems, channel activity and transporter function
Cloned receptors are also available at no cost to qualified investigators.
Assays are now available for bioavailability predictions (CaCo2, MDR-1) and cardiovascular toxicity predictions (HERG, 5-HT2B

Application Process:
To request services from the PDSP you must submit an assay request. Requests are processed by the PDSP Online Database. To create an assay request you first need to be registered as an Investigator. Please use the following tutorial which will help you create an account and submit an assay request: PDSP Assay Request Tutorial. If you already have a PDSP account simply login and initiate a new request.

Requests for screening, assays requested, and supporting information will be submitted to Jamie Driscoll, B.S. at NIMH and Bryan Roth, M.D., Ph.D. at University of North Carolina Chapel Hill.

NIMH and University of North Carolina Chapel Hill will review and prioritize all requests for screening. An assay request’s status can be monitored through the PDSP Online Database’s ‘Assay Request Manager’.

Rapid Access to Preventive Intervention Development (RAPID)

**This program is no longer active**

Chemical Carcinogen Reference Standards Repository

The National Cancer Institute (NCI) contracts with MRI to operate a repository that supplies standard reference-grade compounds for cancer research. The goal of the repository is to provide well-characterized reference standard materials, analytical data, and health and safety information to the carcinogenesis research community.

To effectively serve the carcinogenesis research community, the repository is required to:

Procure chemical samples
Provide for their safe and stable storage until requested by users
Repackage the chemicals to meet user needs
Ensure the uniformity of all samples
Ship samples to users along with the appropriate analytical documentation and safe handling instructions.

425 Volker Boulevard
Kansas City, Missouri 64110-2299 USA
Telephone: (816) 753-7600
FAX: (816) 753-3664 or (816) 753-8420

NCI Chemical Repository, Ext. 1639

Chemical Repository Purchases, Ext. 1510

Natural Products Repository

Since 1986, DTP has acquired plants and marine organisms through collection contracts performed in over 25 tropical and subtropical countries worldwide. As of September, 1999, over 50,000 plant samples have been collected in Africa and Madagascar, Central and South America, and Southeast Asia through contracts with the Missouri Botanical Garden, the New York Botanical Garden, and the University of Illinois at Chicago, assisted by the Arnold Arboretum of Harvard University and the Bishop Museum in Honolulu. During the same period over 10,000 marine invertebrates and marine algae have been collected, mainly from the Indo-Pacific region, through contracts with the Harbor Branch Oceanographic Institute, the Australian Institute of Marine Science, the University of Canterbury, New Zealand, and the Coral Reef Research Foundation. The marine collection contract with the Coral Reef Foundation was renewed in February, 1997. In undertaking these collections, NCI has committed itself to the conservation of biological diversity, as well as to policies of fair and equitable collaboration and compensation in interacting with the Source Countries participating in the collection programs. Agreements based on the NCI Letter of Collection have been signed with relevant government organizations in many of the source countries participating in the collection program.

Each organism is extracted in the Natural Products Extraction Laboratory with a 1:1 mixture of dichloromethane and methanol, and then with water, and the extracts are stored at -20⁰C in the Natural Products Repository. Both these facilities are operated by SAIC at the Frederick Cancer Research and Development Center under contract to the NCI. Both extracts are tested in the NCI cancer cell line screen.

Access To the he Natural Products Repository
NCI considers the Natural Products Repository as a national resource, and extracts from the Repository are available either in vials or in 96 well plates for distribution to qualified organizations through the Open Repository Program and the Active Repository Program. Access to these programs will be subject to signing a Material Transfer Agreement protecting the rights of all parties (see Conditions of Access to Active and Open Repositories).

Pure Chemicals Repository

Library of 140,000 synthetic and pure natural compounds for developing new agents to treat cancer

DTP maintains a repository of synthetic compounds and natural products that are openly available to investigators for research purposes in limited quantities based on inventory. Samples are available at no cost except for shipping charges. It is a uniquely diverse collection of more than 140,000 compounds that have been either submitted to DTP for biological evaluation from a variety of sources worldwide or, in some cases, synthesized under DTP auspices. Importantly, investigators should note that chemical structures of these substances are those assigned by the originator of the material and in the vast majority of cases, the compounds have not been analyzed by DTP for accuracy of structure or for the purity of the sample. Compounds are available through a web-based ordering system; instructions are located at the bottom of this page. It is requested that any publication resulting from use of a sample acknowledge the source of the material as “The NCI/DTP Open Chemical Repository” and include the DTP website address, http://dtp.nci.nih.gov , and the NSC number of the agent.

Compounds are available as either individually vialed samples or in plated 96-well format for screening. The quantity available for distribution in vials will be determined by the current inventory. In addition, the 5 focused NCI plated sets below are available.

NCI Plated Sets for Screening

Challenge Set - 57 diverse compounds with unknown mechanisms of cell kill
Diversity Set I – (no longer available)
Diversity Set II – 1364 compounds
Mechanistic Set - 879 compounds
Natural Product Set - 235 compounds

NCI Plated Set for Combination Studies

COMBO Set - (77 compounds)

Biopharmaceutical Development Program (BDP)

The Biological Resources Branch (BRB) is one of the extramural arms of the Developmental Therapeutics Program (DTP), NCI. The BRB supports preclinical and early (e.g. Phase I) clinical studies of biological response modifiers (BRMs) research in the biomedical community through a program of grants and contracts. These studies assess the effects of novel biological agents and explore relationships of biological responses with antitumor activity. The NCI Preclinical Repository distributes selected agents for peer-reviewed preclinical studies performed by both extramural and intramural investigators. Other contracts support the production and in vivo evaluation, both clinical and non-clinical, of biologicals including monoclonal antibodies, recombinant proteins, nucleic acids, viral vectors, whole-cell therapeutics, and natural products.

The NCI BRB Program Staff provide oversight of the Biopharmaceutical Development Program (BDP) at the National Cancer Institute Frederick campus (NCI-Frederick). The BDP produces a variety of biopharmaceuticals under current Good Manufacturing Practices (cGMP) for Phase I/II human clinical trials or advanced preclinical animal testing. The BDP is operated under contract by Scientific Applications International Corporation (SAIC) Frederick, which provides operations and technical support to the FCRDC.

Resource Guide for the Development of AIDS Therapies (DAIDS)

Databases:
Computerized databases linking chemical structures with preclinical antiviral and antimicrobial efficacy data are maintained to assist DAIDS staff in tracking compounds for further preclinical study. Upon request by academic, government, and private sector investigators, DAIDS staff can search these databases and provide nonproprietary information (obtained from the literature, patents, and public conferences) regarding specific compounds to help guide the investigators’ drug development efforts.

Resource Descriptions

Separate databases are maintained for HIV, OI, and TB therapies
Both in vitro and in vivo biological data are maintained within the databases
Databases contain chemical structure information and can be searched by chemical substructure features
OI databases contain information for Candida albicans, Cryptococcus neoformans, Cryptosporidium parvum, Histoplasma capsulatum, Mycobacterium avium, Pneumocystis carinii, and Toxoplasma gondii
TB databases contain information for both wild type and drug-resistant strains of Mycobacterium tuberculosis

Accessing These Resources

For further information please contact Dr. Mohamed Nasr (phone: 301-496-0636).
Internet access to portions of these databases is available at Database for Anti-HIV Compounds.

Agents with therapeutic potential in the following areas can be evaluated by DAIDS-sponsored contractors for in vitro efficacy:

evaluation of novel anti-HIV therapies:

Biochemical Assays

A variety of virus-specific biochemical assays (e.g. , reverse transcriptase, protease, integrase) are available for the evaluation of compounds and to aid in mechanism of action studies.

In Vitro Efficacy Evaluations

Agents can be evaluated for efficacy against HIV-1 and HIV-2 in established T-cell lines and in primary human peripheral blood mononuclear cells and macrophages. These resources are not available for the screening of previously untested compounds (with the exception noted below), nor for the evaluation of multi-component natural product extracts, but instead are dedicated to confirming and extending preliminary findings of anti-HIV activity generated elsewhere.

Potential therapeutic agents can be evaluated for cytotoxicity and for efficacy against HIV-1and HIV-2 in several established human T-cell lines, peripheral blood mononuclear cells, and macrophages.
Capabilities include evaluation against drug resistant virus isolates, studies of molecular mechanisms of action, and other specialized investigations examining a variety of viral parameters.
Therapeutic agents can be evaluated either alone or in combination with other agents.
Compounds with potential as topical microbicides can be evaluated in cell-free and cell-associated HIV transmission blocking assays. Limited screening of previously untested compounds for this specific task sometimes can be accommodated.

Accessing These Resources

For further information regarding biochemical assays and specialized in vitro efficacy evaluations please contact Dr. Roger Miller (phone: 301-496-8197).
For further information regarding general in vitro efficacy evaluations please contact Dr. Steven Turk (phone: 301-435-3771).
For further information regarding in vivo efficacy evaluations contact Dr. Paul Black (phone: 301-402-2970).

evaluation of novel anti-OI therapies:

In Vitro

Efficacy Evaluations

Potential therapeutic agents can be evaluated for cytotoxicity and for efficacy against Cryptococcus neoformans, Cryptosporidium parvum, Mycobacterium avium, Pneumocystis carinii, and certain microsporidia.
Therapeutic agents can be evaluated either alone or in combination with other agents
Potential therapeutic agents can be evaluated for cytotoxicity and for efficacy against viral opportunistic agents such as Herpes Simplex viruses and Cytomegaloviruses.

Accessing These Resources

For further information regarding C. neoformans, C. parvum, M. avium, or P. carinii please contact Dr. Chris Lambros (phone: 301-402-2304).

For further information regarding non-HIV viruses please contact Dr. Christopher Tseng (phone: 301-496-7453).

evaluation of novel anti-TB therapies:

Compound Acquitision

In Vitro

Efficacy Evaluations

Potential therapeutic agents can be evaluated for cytotoxicity and for efficacy against both wild type and drug-resistant strains of Mycobacterium tuberculosis
Therapeutic agents can be evaluated either alone or in combination with other agents

In Vivo

Efficacy Evaluations

A model utilizing M. tuberculosis infection of mice is available. Microbiologic and histologic parameters can be evaluated.
Compounds are evaluated for in vitro efficacy against the microbial strains used in the model prior to initiating in vivo studies
Therapeutic agents can be evaluated either alone or in combination with other agents
Both anti-tubercular and immune-based therapies can be evaluated.

Accessing These Resources

Dr. Barbara Laughon

Grant Mechanisms

The following describes grant-based funding opportunities for investigators in the areas of drug discovery and basic research:

The NIH Grants and Contracts home page provides links to general information regarding NIH and SBIR/STTR grant mechanisms and to the NIH Guide for Grants and Contracts.
The NIAID Council News – Extramural Information Center home page provides links to specific programs sponsored by The National Institute of Allergy and Infectious Diseases to which investigators can submit applications.
The National Cooperative Drug Discovery Group for Opportunistic Infections (NCDDG-OI) grant program supports consortia of academia, industry, and government investigators working collaboratively on targeted discovery and preclinical development of new OI drugs and therapeutic strategies.

Dr. Barbara Laughon

The Novel HIV Therapies: Integrated Preclinical/Clinical Program (IPCP) supports (1) the discovery and preclinical development of new anti-HIV drugs and therapeutic concepts; and (2) the translation of innovative preclinical findings to the clinic via small clinical studies. This grant program funds consortia of investigators from academia and the private sector, working collaboratively on the development of a defined therapeutic concept identified and proposed by the collaborative group. This mechanism is particularly appropriate for highly experimental therapeutic strategies that are new or otherwise not yet ready for large clinical trials.
- Validation of the analytical methods for quantitating drug concentrations in dosing solutions, biological fluids, and tissues, as required. Determination of plasma drug levels in animals administered the agent under study, and calculation of pharmacokinetic parameters derived from these data.
- Determination of bioavailability of the drug after different routes of administration, including oral, intravenous (i.v.), subcutaneous (s.c.), intramuscular (i.m.), or intraperitoneal (i.p.), as needed. Calculation of the pharmacokinetic parameters from the derived data.
- In vitro evaluation of hepatotoxicity in human and animal liver cells.
- Preclinical acute toxicity evaluations on lead compounds, evaluating clinical observations, body weights, clinical pathology, histopathology, and plasma drug levels in rodents and non-rodent species. Other toxicology endpoints may be selected if needed.
- Subacute and subchronic toxicity evaluations in rodents and large animal species, evaluating clinical observations, body weights, clinical pathology, and histopathology.
- G enotoxicity assessments using a battery of appropriate assays.
- The applicant’s institution must be a U.S. domestic institution.
- All applicants must have a currently active NIH grant from one of the participating NIH institutes. The Travel Fund and the Workshop Fund will be provided as an administrative supplement to the applicant’s parent grant. The goals of the collaborative research/training and workshop must be related to the research areas of the parent grant.
- The Travel Fund supplements the travel and lodging expenses of the U.S. scientist’s visit to Japan.
- The total direct cost of each Travel Fund may not exceed $15,000. Up to $2,500 of the funding amount may be used for research supplies. Funds from the BRCP may not be used as salary support to the principal investigator (PI), co-investigators, or collaborators.
- The visit to the Japanese institution may be performed by the PI, co-investigators, postdoctoral fellows or students who work on the collaborative project. The travel fund can be used for one or multiple trips. Travel costs should not exceed the U.S. Government Foreign Per Diem Rate for Japan (http://www.state.gov/m/a/als/prdm/)
- The duration of the supplement is one year. The supplement may be carried over into the next fiscal year, with prior approval from NIH program staff.
- The Workshop Fund provides partial support for joint workshops. The total direct cost of each workshop fund may not exceed $35,000. The support of travel and lodging expenses should not exceed the U.S. Government Per Diem Rates. No honorarium is allowed. Applicants are encouraged to obtain additional support from other sources.
- Each component (U.S. or Japanese) of the BRCP will supplement the travel and lodging expenses of the joint-workshop participants from their own country. Applicants are encouraged to use the Workshop Fund to compensate the travel and lodging for women and underrepresented minority investigators, junior investigators, postdoctoral fellows, and graduate students.
- If the joint workshop is to be held in Japan, the Japanese component of the BRCP will support the logistical meeting expenses. If the joint workshop is to be held in the U.S., the U.S. component of the BRCP will support the logistical meeting expenses.
- Synthesis of ligands for CNS receptors, radiolabeled compounds for autoradiography and neuroimaging, biochemical markers, drug analogs and metabolites, and reference standards.
- GLP and GMP synthesis of promising compounds for toxicology and safety studies, especially compounds for PET neuroimaging.
- Compounds currently available in stock are listed in the NIMH Repository , available on-line at the web site http://nimh-repository.rti.org.
- A brief summary of the significance of the compound to the investigator’s research and an indication of the importance of the research to neuroscience.
- A description of the protocols to be employed with the compounds, and detailed justification on the amounts required. For in vivo assay, please include information on projected dose levels, number of animals, etc., so that the calculations support the requested amount.
- Current IACUC or IRB assurances, if appropriate.
- Primary source of financial support for the proposed research.
- For radiolabeled compounds, a copy of the institution’s current NRC license showing the authorized amount of the specific isotope and the license expiration date.
- For synthesis requests, please include information on prior sources of the compound or related compounds, if available. Literature citations relevant to the synthesis of the target compound or related compounds are essential to the evaluation of the request. Please note that requests for GLP or GMP synthesis will require additional information and another level of review. Please contact Jamie Driscoll at NIMH.

National Technology Centers for Networks and Pathways (TCNP)

Development of Clinical Imaging Drugs & Enhancers (DCIDE)

The Development of Clinical Imaging Drugs & Enhancers (DCIDE) program is a competitive program to expedite and facilitate the development of promising investigational imaging enhancers (contrast agents) or molecular probes from the laboratory to IND status. Through the DCIDE program, the developer of a promising diagnostic agent or probe will be given access to the pre-clinical development resources of the National Cancer Institute in a manner that is intended to remove the most common barriers between laboratory discoveries and IND status.

Through the DCIDE program, the developer of a promising diagnostic agent or probe will be given access to the pre-clinical development resources of the National Cancer Institute in a manner that is intended to remove the most common barriers between laboratory discoveries and IND status.

Application:

No more than two requests for support from the same principal investigator may be received on any given receipt date. An individual agent has three chances to be approved by DCIDE. After three unsuccessful attempts, subsequent requests focusing on the same agent will be returned without review.

Please use the PHS 398 form to request support. Send original and 4 copies to the contact person. http://imaging.cancer.gov/programsandresources/specializedinitiatives/dcide/page6

Type 1 Diabetes (T1D) Special Statutory Funding Program

The Type 1 Diabetes – Rapid Access to Intervention Development (T1D-RAID) program is designed to assist translation to the clinic of novel therapeutic interventions for type 1 diabetes and its complications. These potential interventions can be either synthetic, natural product, or biologic. Requests to T1D-RAID are brief (20 pages or less), and should clearly outline the resources required to ready the proposed therapeutic agent for clinical trials.

Requests are accepted twice yearly, on November 1 and April 1. The requests are reviewed by a panel of extramural experts within two to three months of receipt. Review criteria include strength of the scientific hypothesis, scientific novelty, and cost/benefit considerations afforded by the proposal.

T1D-RAID is not a grant mechanism. Approved requests to T1D-RAID gain access to the drug development contract resources of the National Cancer Institute’s Developmental Therapeutics Program (NCI DTP). The output of the use of these resources is provided to the originating investigator, and may include GMP synthesized material, formulation research, pharmacological methods, or IND-directed toxicology, for support of an investigator-held IND application and clinical trials. T1D-RAID does not sponsor clinical trials; it sponsors the work needed to get ready to do clinical trials.

For more information on services that may be available, visit http://dtp.nci.nih.gov/docs/raid/raid_index.html

The output of T1D-RAID activities will be both products and information that will be made fully available to the originating investigator for support of an IND application and clinical trials. T1D-RAID does not sponsor clinical trials. However, NIDDK has other programs such as the Type 1 Diabetes TrialNet (http://www.diabetestrialnet.org/en/public/index.html) and Immune Tolerance Network (http://www.immunetolerance.org/) that may provide support for subsequent clinical trials.

Application:
NIDDK will receive requests twice per year (April 1 and November 1). A letter of intent is encouraged one month prior to submission of a Request. Requests will consist of a written description of the request, a technology transfer form, and, if required, a letter of commitment from the investigator’s institution indicating support for the clinical trial (see B. Components of the Request for additional details). The Request itself should be no more than 15 single-spaced pages (Public Health Service grant application materials ARE NOT required). No more than two requests for support from the same principal investigator may be received on any one receipt date. An individual product has three chances to be approved by T1D-RAID. After three unsuccessful attempts, subsequent requests focusing on the same product will be returned without review.

Animal Models of Diabetic Complications Consortium (NIDDK)

The AMDCC is an interdisciplinary consortium designed to develop new animal models that closely mimic the human complications of diabetes for the purpose of studying disease pathogenesis, prevention and treatment. The consortium consists of thirteen “pathobiology sites” that study complications such as diabetic nephropathy, uropathy, neuropathy, cardiomyopathy and vascular disease.

Additional goals of the AMDCC are to define criteria to validate each diabetic complications for its similarity to the human disease, test the role of candidate genes that emerge from human genetic studies, and facilitate the exchange of models, tissues, reagents, and expertise between members of the consortium and the greater scientific community.

To ensure that all models generated by the AMDCC are phenotyped for a full duration of diabetes and across all relevant complications, the consortium has formed a close partnership with the Jackson Laboratories and the NIDDK-funded Mouse Metabolic Phenotyping Centers.

Mouse metabolic phenotyping centers (NIDDK)

The mission is to advance medical and biological research by providing the scientific community with standardized, high quality metabolic and physiologic phenotyping services for mouse models of diabetes, diabetic complications, obesity and related disorders.

The six Centers are housed at outstanding academic institutions, staffed by experts in state-of-the-art technology. Researchers can ship mice to one of the Centers and obtain on a fee-for-service basis a range of complex exams used to characterize mouse metabolism, blood composition including hormones, energy balance and physical activity, eating and exercise, insulin resistance, organ function, metabolic fluxes and morphology, physiology, histology and measures of diabetic complications in heart, kidney, vasculature, eye, etc. Many tests are done in living animals and are designed to elucidate subtle to complex traits that would define models of metabolic disease.

The development of transgenic technology and gene targeting protocols has resulted in numerous mouse lines with specific phenotypes and well-defined DNA structural changes. Candidate genes for diabetes, obesity and other disorders of metabolism have been identified and transgenic mice are being generated using this technology. By broadening the availability of sophisticated metabolic phenotyping, we hope to help investigators identify and study new mouse models that will lead to an improved understanding of these complex diseases.

In 2006, the MMPC formed a collaboration with the NIH-sponsored Animal Models of Diabetic Complications Consortium (AMDCC) in order to more thoroughly phenotype putative new mouse models of disease for a range of complications including cardiovascular disease, nephropathy, neuropathy, retinopathy. The MMPC is committed to improving access to existing tests, and to developing new technologies for this purpose.

Toxicological Evaluation of Novel Ligands Program

The purpose of the NIMH Toxicological Evaluation of Novel Ligands Program is to accelerate the discovery, development, and application of novel ligands for PET, SPECT, and MRI imaging in humans by providing toxicology and safety assessment of promising, target-selective compounds. The program will also provide limited assessment of novel psychoactive agents for clinical research and as potential therapeutics. Toxicology and safety data generated by the program will be used to support an Investigational New Drug (IND) application to the Food and Drug Administration (FDA), or for Radioactive Drug Research Committee (RDRC) evaluation of a compound for human studies. The contract will evaluate toxicity and safety of compounds submitted for testing which may include, but are not limited to, novel chemical entities, structural analogs of compounds with an IND, or analogs of FDA-approved drugs. The services available under this program fall under four general phases: (1) analytical, (2) pharmacokinetics, (3) preliminary safety, and (4) IND-directed toxicity including safety pharmacology.

What is available?
A broad range of tasks are available for assessing the safety and/or pharmacokinetics of each ligand. Specific capabilities available to investigators include:

Since these preclinical studies are needed to demonstrate to the FDA that a candidate medication or imaging agent is understood well enough for designing appropriate clinical treatment regimens, most of the work to be conducted to achieve these objectives must be performed and the resulting data analyzed and reported in strict compliance with the FDA’s GLP regulations for nonclinical laboratory studies (21 CFR 58). These data must be obtained by carefully planned and skillfully executed methods that are specific, accurate, and precise. The applicable portions of the accumulated safety data will be included in documents submitted to the FDA in support of regulatory applications.

How to submit requests
Please use the NIMH ORDER FORM. NIMH and SRI will review and prioritize all requests for toxocological and pharmacokinetic development. Supporting information should be submitted by e-mail (or fax) to Jamie Driscoll at NIMH and Hanna Ng at SRI following an initial consultation.

US-Japan Brain Research Cooperative Program (BRCP)

The purpose of the BRCP is to promote scientist exchange, training, and research collaborations between neuroscientists from the U.S. and Japan. The U.S. component of the BRCP supports the following activities: 1) Visit of U.S. scientists to conduct collaborative research and/or to acquire advanced research skills in Japanese institutions, 2) Joint workshops to exchange scientific information and to foster collaborations.

Eligibility

Mechanisms of Support

Travel Fund

Workshop Fund

How to Apply

Approval from program staff at the respective participating NIH institute is required prior to the submission of applications. Applications submitted without prior approval will be returned (See “Inquiries” section of this Notice).

All applications must be received by the Neuroscience Center at the address provided below on or before September 15 of each participating year. Applicants should submit one electronic copy of their application, as an e-mail attachment, in PDF format and one original, signed by the U.S. applicant and the administrative official from his or her home institution. Applications should be sent to the following address:

Stacey Chambers
Office of International Activities
National Institute of Neurological Disorders and Stroke
Neuroscience Center, Room 2179
6001 Executive Boulevard
Rockville, MD 20852
Phone: 301-496-0690
Fax: 301-480-1080
Email: chambers@ninds.nih.gov

DO NOT SEND APPLICATIONS TO THE NIH CENTER FOR SCIENTIFIC REVIEW

HTS Assay Development Interest Group (HADIG)

**No longer active**

NIMH Chemical Synthesis and Drug Supply Program

Since 1959, the NIMH Chemical Synthesis Program has synthesized and distributed novel research chemicals, psychoactive drugs, and compounds that are unavailable from commercial sources to the scientific community working on research relevant to mental health. The purpose of the present the NIMH Chemical Synthesis and Drug Supply Program is to synthesize, purify, and distribute otherwise unavailable essential compounds to stimulate basic and clinical research in psychopharmacology relevant to mental health in areas such as the molecular pharmacology and signaling of CNS receptors, longitudinal studies to evaluate the molecular, biochemical, and behavioral actions of psychoactive compounds, and functional brain imaging in both primates and humans. The NIMH has recently contracted with RTI International to operate the NIMH Chemical Synthesis and Drug Supply Program.

What is available?

Eligibility
Investigators involved in basic or clinical research relevant to mental health. To learn more about current research areas, please visit the NIMH Research Web Areas at http://www.nimh.gov/research/nimhwebs.cfm. NIMH Repository compounds are pro-vided free to qualified academic investigators.

How to Submit Requests
Requests for repository compounds and for the synthesis of compounds, together with supporting information, should be submitted on the NIMH Order Form located at the repository web site http://nimh-repository.rti.org. Alternatively, requests may be mailed to Jamie Driscoll (NIMH) or Ken Rehder (RTI International) ( please see contact information).

Investigators interested in obtaining radiolabeled compounds but uncertain about what type of label or specific activity would work best for them may obtain help by contacting Jamie Driscoll (NIMH) or Anita Lewin (RTI International) (see contact information).

Requests Should Include:

ChemBank

ChemBank is a public, web-based informatics environment created by the Broad Institute’s Chemical Biology Program and funded in large part by the National Cancer Institute’s Initiative for Chemical Genetics (ICG). This knowledge environment includes freely available data derived from small molecules and small-molecule screens, and resources for studying the data so that biological and medical insights can be gained. ChemBank is intended to guide chemists synthesizing novel compounds or libraries, to assist biologists searching for small molecules that perturb specific biological pathways, and to catalyze the process by which drug hunters discover new and effective medicines.

ChemBank stores an increasingly varied set of cell measurements derived from, among other biological objects, cell lines treated with small molecules. Analysis tools are available and are being developed that allow the relationships between cell states, cell measurements and small molecules to be determined. Currently, ChemBank stores information on hundreds of thousands of small molecules and hundreds of biomedically relevant assays that have been performed at the ICG in collaborations involving biomedical researchers worldwide. These scientists have agreed to perform their experiments in an open data-sharing environment.

The goals of ChemBank are to provide life scientists unfettered access to biomedically relevant data and tools heretofore available almost exclusively in the private sector. We intend for ChemBank to be a planning and discovery tool for chemists, biologists, and drug hunters anywhere, with the only necessities being a computer, access to the Internet, and a desire to extract knowledge from public experiments whose greatest value is likely to reside in their collective sum.

NIEHS National Toxicology Program HTS Initiative

As an extension of the NIH Roadmap, NTP established a High Throughput Screening (HTS) program, representing a new paradigm in toxicological testing. NTP is using this HTS approach to screen for mechanistic targets active within cellular pathways critical to carcinogenicity, reproductive and developmental toxicity, genotoxicity, neurotoxicity, and immunotoxicity. NTP’s HTS program is administered through the newly created Biomolecular Screening Branch (BSB).

Through a memorandum of understanding (MOU) (see February 2008 News Release), the NTP is partnering with the National Human Genome Research Institute’s NIH Chemical Genomics Center (NCGC) (http://www.ncgc.nih.gov/index.html) and the U.S. Environmental Protection Agency’s National Center for Computational Toxicology ToxCast^TM program (http://www.epa.gov/comptox/), located within the Office of Research and Development, to test a large number of compounds (~ 8,000) broadly characterizing and defining the chemical-biological space occupied by chemicals of toxicological concern.

Application Process:

For further information on NTP’s High Throughput Screening program, contact:

Raymond Tice, Ph.D.
Chief, Biomolecular Screening Branch
NIEHS/NTP
P. O. Box 12233, MD K2-17
111 T. W. Alexander Drive
Durham, NC 27713
T: (919) 541-4482
F: (919) 541-0947

Beta Cell Biology Consortium (BCBC)

The Beta Cell Biology Consortium (BCBC) is a team science initiative that was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2001 (RFA DK-01-014), and competitively continued in 2005 (RFA’s DK-01-17, DK-01-18). Currently, the BCBC consists of 29 scientists, the majority of whom participate as either Principal or Co-Principal Investigators on eight U-01 and two U-19 projects. In addition, scientists from two intramural NIDDK laboratories are involved.

Activities within the BCBC are overseen by both NIDDK staff members and participating scientists. A Steering Committee, which consists of all Principal Investigators, meets on a semi-annual basis. An Executive Committee meets monthly by teleconference. An External Advisory Board serves to provide objective scientific input and guidance.

A Coordinating Center located at Vanderbilt University provides the organizational infrastructure for the BCBC. Its primary objectives are to 1) facilitate interactions and communication by organizing meetings and retreats, distributing announcements, and maintaining a website with databases of vital research resources; 2) support research within the BCBC by organizing core facilities and, when necessary, developing new cores; 3) jumpstart new research by young investigators through a Pilot and Feasibility (P&F) Grant Program; and 4) bring different groups of scientists together within the BCBC through a Program of Collaborative Bridging Projects.

Many of the BCBC investigator-initiated projects involve reagent-generating activities that will benefit the larger scientific community. The combination of programs and activities that, together comprise the BCBC, should accelerate the pace of major new discoveries and progress within the field of beta cell biology.

Nuclear Receptor Signaling Atlas (NURSA)

The Nuclear Receptor Signaling Atlas (NURSA) was created to develop a comprehensive understanding of the structure, function, and role in disease of nuclear receptors. While the Atlas was begun as a Functional Atlas of Orphan Nuclear Receptors to elucidate the roles played by orphan nuclear receptors in metabolism and the development of metabolic disorders (including type 2 diabetes, obesity, osteoporosis, and lipid dysregulation), as well as in processes of aging and hormone-dependent cancers, the present goal of the Atlas consortium is to expand this effort to encompass all nuclear receptors.

To accomplish these objectives, the members of the consortium form a team dedicated to catalyzing progress in understanding of the complex interplay between and among nuclear receptors and coregulators, with the goal of expediting translation of basic findings into tools that can find clinical applications. The goal is to approach research questions that require complex technologies which are not easily performed in an individual investigator’s laboratory, and in an interdisciplinary mode.

The intent is to accumulate validated data, and to make it available rapidly to interested scientists at large via electronic communication on the NURSA website (www.nursa.org). Through this website, the Atlas is designed to reach out to all interested members of the nuclear receptor research community to provide new findings, access to new reagents, large validated data sets, a library of annotated prior publications in the field, and our reviews & techniques journal, Nuclear Receptor Signaling.

Contact person: Ronald Margolis, Ph.D. (Phone: 301-594-8819)

NIDDK Clinical Tissue Repository

NIDDK maintains a Clinical Tissue Repository serving as a rich source of well-characterized biological samples from major clinical studies that are suitable for validating hypotheses about the presence or absence of various analytes. Tens of thousands of immortalized B-cell lines suitable for biological assays are available through the repository. The samples are from patients and have significant accompanying phenotypic data.

Contact person: Rebakah Rasooly, Ph.D.

Characterization of NCI60 cell lines

The cell lines in the NCI60 screen have undergone a large number of characterizations, including multiple microarray gene expression measurements. It is also possible to get materials from DTP to do your own measurements. Testing in the NCI 60 can give very useful information about a compound. The pattern of activity has been found to be related to the mechanism of action and this is the basis for the COMPARE program (see http://dtp.nci.nih.gov/docs/compare/compare.html). The pattern of activity can help in the determination of the mechanism of action of a novel compound, can suggest diverse compounds that might share a mechanism of action, and can suggest compounds whose mechanism of action is unique compared to the ~100K compounds that have been through the NCI 60. In addition, a significant amount of work has gone into characterizing the 60 cell lines (see http://dtp.nci.nih.gov/mtargets/mt_index.html) and thus there is a rich set of data (including gene expression measurements) that can be mined for correlations to compound action.

Chemical Biology Consortium (CBC)

This program will provide much more complete early discovery resources. The contracts are in competition and it is expected that policy and procedures for submitting projects will be in place in spring 2009.

Drug Development Group

This program provides the same services as RAID, but in cases where the IND will be held by NCI. There is an application process, but it requires consultation with DTP staff ahead of time to confirm DTP interest.

Follow up PAs and RFAs for ML investigators:

NIDA

- PAR-11-109 (U01) Grand Opportunity in Medications Development for Substance-Related Disorders
- PAR-11-102 (X02) Pre-Application for the 2011 NIDA Translational Avant-Garde Award for Medication Development for Diseases of Addiction
- PAR-10-213 (R01) Development of Assays for High-Throughput screening for use in Probe and Pre-therapeutic Discovery
- PAR-10-001 (R01), PAR-10-002 (R21) Drug Discovery for Nervous System Disorders
- PAR-09-251 (R21), PAR-09-259 (STTR[R41]), PAR-09-260 (SBIR [R43]) Optimization of Small Molecule Probes for the Nervous System
- Medications Development for Polydrug Addiction Treatment
  PAS-08-186 (R01), PAS-08-187 (R21)

NIMH

- PA-11-133 (R43, R44) Complex Technologies and Therapeutics Development for Mental Health Research and Practice
- PAR-10-216 (P01) Novel NeuroAIDS Therapeutics: Integrated Preclinical/Clinical Program
- PAR-08-142 (R43, R44) Pharmacologic Agents and Drugs for Mental Disorders
- PA-11-135 (R44) Phase IIB Grants for Brain and Behavior Tools (R44)
- PA-10-081 (R43, R44) Novel Tools for Investigating Brain Derived GPCRs in Mental Health Research
- PAR-10-213 (R01) Development of Assays for High-Throughput screening for use in Probe and Pre-therapeutic Discovery
- PAR-10-001 (R01), PAR-10-002 (R21) Drug Discovery for Nervous System Disorders
- PAR-09-251 (R21), PAR-09-259 (STTR[R41]), PAR-09-260 (SBIR [R43]) Optimization of Small Molecule Probes for the Nervous System

NINDS

- RFA-NS-12-001 (R25) NIH Blueprint for Neuroscience Research Short Courses in Neurotherapeutics Development
- PAR-10-144 (U01) NINDS Cooperative Program in Translational Research for Resistant Epilepsy and Epileptogenesis
- PAS-10-183 (R01) Validation of Novel Therapeutic Targets for Huntingtons Disease
- PAR-10-213 (R01) Development of Assays for High-Throughput screening for use in Probe and Pre-therapeutic Discovery
- PAR-10-001 (R01), PAR-10-002 (R21) Drug Discovery for Nervous System Disorders
- PAR-09-251 (R21), PAR-09-259 (STTR[R41]), PAR-09-260 (SBIR [R43]) Optimization of Small Molecule Probes for the Nervous System

NIDDK

- PAR-10-213 (R01) Development of Assays for High-Throughput screening for use in Probe and Pre-therapeutic Discovery
- RFA-DK-10-012 (DP3) Type I Diabetes Impact Award
- PA-09-181 (R01) Non-Invasive Methods for Diagnosis and Digestive Diseases and Hypertensive Disorders

NHLBI

- PA-11-121 (R01) Ribosomal Disorders and Their Role in Inherited Bone Marrow Failure Syndromes
- PA-10-213 (R01) Development of Assays for High-Throughput Screening for Use in Probe and Pre-therapeutic Discovery

NIAID

- RFA-AI-11-004 (R01) Chemical Approaches to Target Validation for Drug Resistant Pathogens
- PA-10-213 (R01) Development of Assays for High-Throughput Screening for Use in Probe and Pre-therapeutic Discovery

NIAAA

- PA-10-085 (R01), PA-10-186 (R21) The Role of Cellular Organelles in Alcohol-Induced Tissue Injury
- PA-10-213 (R01) Development of Assays for High-Throughput Screening for Use in Probe and Pre-therapeutic Discovery

NIA

- PA-10-164 (R21) Identification and Characterization of Molecular Targets Within the mTOR Pathway With Potential to Impact Healthspance and Lifespan
- PAS-10-151 (R21) Grants for Alzheimers Disease Drug Discovery

NIAMS

- PAR-10-282 (R21) Pilot and Feasibility Clinical Research Grants in Arthritis and Musculoskeletal and Skin Diseases
- PA-10-213 (R01) Development of Assays for High-Throughput Screening for Use in Probe and Pre-therapeutic Discovery

NEI