Attachment No. 3 PDSP SOW 05032022.pdf

STATEMENT OF WORK (SOW)

TITLE: NIMH PSYCHOACTIVE DRUG SCREENING PROGRAM (PDSP)

I. BACKGROUND AND OBJECTIVES:

The mission of the National Institute of Mental Health (NIMH) is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.

Within the NIMH, the mission of the Molecular and Cellular Neuroscience Research Branch is to support fundamental research on the mechanisms underlying and influencing neuronal signaling, synaptic plasticity, signal transduction pathways, and the biochemical and behavioral actions of therapeutic agents in animals and humans. The goals of the branch include the identification of novel targets (genes or molecules) for therapeutic intervention, characterization of the neurobiological and behavioral actions of psychoactive agents, and design and development of novel ligands for functional brain imaging in humans, psychoactive agents for basic and clinical research, and potential therapeutic agents for the treatment of mental disorders.

To further these goals, a requirement for the NIMH Psychoactive Drug Screening Program (PDSP) was initiated to provide broad-based screening capabilities, in the form of pharmacological and functional assays and receptor binding data to the scientific research community with the intent of stimulating innovative research and development efforts in the design of novel psychoactive compounds for preclinical research, neuroimaging, and as potential therapeutic agents in the treatment of psychiatric disorders. The program focuses on the use of state-of-the-art, high-throughput screening (HTS) of compounds in human and rodent central nervous system (CNS) binding and functional assays.

The purpose of the NIMH PDSP is to provide screening of novel synthetic compounds and natural products for potential use as research tools or probes for basic and clinical research, as therapeutic agents for mental disorders, and as PET, SPECT, and fMRI ligands for functional brain imaging. This program is primarily intended as a screen for compounds that have previously been shown to possess pharmacological, biochemical, or behavioral activities relevant to NIMH and not for the purpose of large-scale, random screening of natural products or combinatorial libraries (e.g., libraries containing >1000 compounds).

However, screening maybe conducted on small libraries of synthetic or natural product compounds of unknown activity and on hit or lead compounds generated through NIH-funded HTS or chemistry programs.

Compounds will be provided by the research community, primarily NIH-supported investigators. It is anticipated that the Contractor will receive and screen compounds on a continuous and on-going basis, although the volume of requests will vary from month to month.

II. SERVICES TO BE PERFORMED:

Independently and not as an agent of the federal government, the contractor shall be required to furnish all the necessary services, qualified and experienced personnel, equipment, material, supplies, and facilities, not otherwise provided by the Government, as needed to perform services in this Statement of Work (SOW).

tative (COR) whose responsibilities will be defined in the resultant contract.

A. General Requirements

The objectives of the requirement are to receive and test approximately 2,500-3,000 samples (e.g., small molecules, gene products, and natural product extracts) per year, as specified by SOW, in broad-based human and rodent CNS screening assays, and to provide an electronic data file for each of the screened compounds. Samples for screening can include, but are not limited to, novel chemical entities, structural analogs of lead compounds, gene products, and natural products. It is anticipated that NIMH-approved samples will be submitted in individual vials or in a plated format from NIH-funded research programs, academic research programs, or other sources. It is expected that the screening information derived from this program will provide individual investigators with data addressing the specificity and/or activity of compounds at CNS targets.

B. Specific Technical Requirements

1. Overview of the Sample Screening Process

a. Investigator contacts Contractor or COR) regarding submission of samples to NIMH screening program;

b. Investigator submits a screening request through the Contractor web-based request system;

c. Contractor appraises the request and forwards a recommendation to COR within one (1) week of receipt;

d. COR approves, amends, or denies the request based on Contractor's appraisal and NIMH programmatic considerations;

e. Contractor sends empty sample vials to investigator within three (3) business days of COR approval of assay request;

f. Investigator returns samples to Contractor at own expense and provides sample information and handling instructions;

g. Sample(s) received by Contractor, will be stored according to any instructions received from the submitting investigators (e.g., storage under specific temperature requirements) and scheduled for assays;

h. Pharmacological assays, binding affinity and/or functional assays will be performed using the highest standards and following approved assay protocols;

i. Data analysis and assay report are generated and made available to the COR and submitting investigator within one (1) week of completion of screening and/or data analysis.

2. Required Assurances and Project Protocols

a. When live vertebrate animals are used to fulfill requirements in the SOW, the Contractor must have an Institutional Animal Care and Use Committee (IACUC) approval to ensure compliance with the National Institutes of Health (NIH) guidelines. The Contractor shall apply to the Office for Laboratory Animal Welfare (OLAW) at the NIH for a project assurance number, if such a number has not been assigned to the Contractor by OLAW. By obtaining a project assurance, the

Contractor agrees to maintain compliance with the NIH guidelines for care and use of vertebrate animals. Institutions must have an Assurance on file with OLAW to receive NIH funding. If the

Institution does not have a valid Assurance, the contractor must negotiate an Assurance with

OLAW prior to receiving any contract award. When human tissue is used, the Contractor must obtain an Institutional Review Board (IRB) approval, as necessary, and a project assurance number from the Office for Human Research Protections (OHRP) prior to fulfilling requirements in the

SOW.

b. The Contractor shall submit, within two (2) weeks after contract award, a detailed protocol for quality control measures and a quality assurance plan to ensure high-quality work and reliability of sample storage and handling and conduct of pharmacological and functional assays.

c. The Contractor shall submit, within two (2) weeks after contract award, a detailed data management protocol describing how data will be stored, handled, analyzed, and shared with the

Government and submitting investigators.

3. Processing Requests, Sample Receipt and Sample Storage.

a. The Contractor shall design, host, and maintain pages on the web with the following information

i. a description of the NIMH Psychoactive Drug Screening Program

ii. procedures for submitting samples for screening

iii. a list of the available assays, descriptions of assay conditions and/or assay protocols; and

iv. a sample information and handling form.

The website shall include the assay request form and shall have the capability for online request submission and COR review and approval of requests for services. The request form must include investigator contact information and source of support, the list of compounds to be tested, the list of assays requested, the rationale for testing the compounds and how it will benefit the relevance of the work to the NIMH mission and Strategic Plan

(https://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml), and any known activity of the compounds. Where applicable, the request should indicate primary target and intended therapeutic indication. The request process shall also include an agreement by the investigator to acknowledge the PDSP in publications using data generated through the program and to inform the program of publications and patents which include PDSP data. To the extent practicable, data fields in the request form should be standardized and searchable to support analysis and evaluation of the program and its impact.

b. The Contractor shall review assay requests from investigators and make recommendations for screening of requested samples within one (1) week of receiving the request. The Contractor shall provide a recommendation to approve or deny the request, any suggested changes to the assays requested, and a priority designation based on their evaluation of the potential impact and urgency of the request. The COR will approve and prioritize all sample screening requests based on the

c. After a sample has been approved for screening by the COR, the Contractor shall package and ship coded sample vials and sample information sheets to the investigator via overnight express delivery. The Contractor will be responsible for the shipment and associated costs of sample vials to investigators. Investigators will be responsible for paying the costs of returning the coded sample vials containing the appropriate amount of sample to be tested and sample information sheets to the Contractor.

d. The Contractor shall develop and maintain an electronic chronological log of sample receipt, handling, and storage conditions. When a sample is received, the following entries shall be made:

1) sample identification number or name; 2) source of compound (investigator name affiliation, phone, fax, and e-mail); 3) date of receipt; 4) sample storage information such as stability, light sensitivity, temperature, etc.; and 5) sample handling requirements such as solubility, preferred solvent, and stability in solution.

e. The Contractor shall store samples as specified by the investigator.

f. All proprietary and non-proprietary samples or compositions of matter submitted for testing for this requirement shall be disposed of by the Contractor within sixty (60) calendar days after the sample assays, data analyses, and sample assay reports have been completed and approved by the

COR. Samples may be returned to the submitting investigator upon request or disposed of in compliance with all relevant environmental and safety regulations.

g. Non-proprietary data (i.e., data derived from compositions of matter in the public domain) generated from services in the SOW shall be disseminated to individual investigators upon written approval by the COR. Non-proprietary data generated from services in SOW may be provided as a resource on the web pages maintained by NIMH and the Contractor upon written approval by the

COR.

4. Confidentiality and Intellectual Property and Patents Rights

a. The Contractor shall protect the confidentiality and intellectual property rights to any sample or composition of matter submitted for testing, including data, product designs/chemical structures, or any other data or material provided to the Contractor. The Contractor shall not use samples supplied by investigators for non-contract related research. The Contractor shall not publish any data generated from any sample submitted for testing under the contract, without prior written approval by the COR.

b. The compound supplier may also request the Contractor to sign agreements like those found at https://www.ott.nih.gov/resources. While the majority of compound suppliers do not request these agreements, a small percentage do require the agreement to protect their rights and liabilities.

c. The Contractor shall assume the intellectual property and patent rights for any invention related to pharmacological or functional assays, data analysis methodologies, or data management systems developed or modified under the contract. The Contractor shall notify the COR and Contracting

Officer (CO) thirty (30) days in advance of the submission of any inventions or publications resulting from services performed in the SOW.

5. Screening Assays

a. Pharmacological Screening: Radioligand Binding and Enzyme Assays

(1) The Contractor shall provide state-of-the-art, high-throughput screening to evaluate samples submitted to the program (synthetic compounds, gene products, and natural product extracts), as approved by the COR, in broad-based pharmacological assays (e.g., radioligand binding and enzyme assays).

(2) Pharmacological screening capabilities shall consist of state-of-the-art binding assays using cloned human and rodent CNS targets. Targets shall include, but are not limited to, serotonin, dopamine, glutamate, GABA, adrenergic, opioid, muscarinic, and histamine receptor subtypes, ion channels, transporters, neuropeptide receptors, second messengers, and enzyme assays (e.g., phosphodiesterase types, tyrosine hydroxylase, tryptophan hydroxylase) as specified in the attached list of assays of interest to NIMH (see Appendix

1). It is desirable that assays for both human and rodent targets are available. Additional assays not included in the Appendix 1 may be proposed if they have clear relevance to neuroscience research and/or CNS drug discovery. Note to offeror: For any assay listed in Appendix 1 that is not currently available, offerors should describe a plan and timeline for developing and validating the assay and making it available for use in the NIMH PDSP.

(3) Primary Pharmacological Assays. The Contractor shall screen each sample in one or more assays, as requested by an Investigator and authorized by the COR. It is anticipated that approximately 35,000 assays may be requested per year. A standard reference compound or compounds shall run simultaneously with each sample or batch of samples tested in a given assay (e.g., in a 96 well plate or equivalent format). As necessary, the COR may ask the Contractor to perform radioligand-binding assays using cell membrane preparations obtained from tissues instead of stably transfected cells.

(4) Secondary Pharmacological Assays. Quantitative analysis of binding affinity will be determined for each sample meeting specified binding criteria, as detailed in the assay protocol (e.g., that produces at least 75% inhibition of specific binding in a given receptor or enzyme assay). A competition curve for the sample shall be generated in duplicate consisting of six to eight concentrations. A standard reference compound shall simultaneously run for each assay performed on a sample or batch of samples. It is anticipated that approximately 10,000 secondary pharmacological assays will be requested per year. The anticipated time frame for completion of the quantitative analysis of sample binding affinity is one to two weeks after completion of primary screening.

(5) A small subset of projects (e.g., PET ligand development) may require the Contractor to conduct estimations of the number of binding sites (Bmax) and affinity (Kd or Ki) on receptor expressed in vitro and in human brain subregions in situ, using post-mortem brain samples provided by the requesting investigator or obtained from COR-approved sources

(e.g., brain banks).

(6) The Contractor shall provide a graph containing the individual competition curves obtained for each sample in a given assay and the competition curve(s) for the standard reference compound(s) plotted as log drug concentration on the abscissa and % specific binding on the ordinate. Data shall be summarized in terms of key pharmacologic parameters (e.g., IC50, Ki (equilibrium dissociation constant), nH, and standard ratio). Mean + SEM, mean and confidence limits, or mean and range shall be determined for each of the values.

(7) The anticipated time frame for accomplishing the screening and data analysis is 4-8 weeks after receipt of the sample. Assay reports shall be prepared and sent to the COR

(electronically) and to the requesting investigator using a secure web-based interface.

b. Functional Screening: Cellular Assays

(1) Functional Assays. Based on historical volume, the Contractor will provide an estimated

125,000 functional assays per year to determine the in vitro agonist, partial agonist, or antagonist properties of samples as specified by the COR. Functional assays may be done as primary, high-throughput screens for activity or as follow-up to binding assays. Cellular assays shall include, but are not limited to, uptake assays for transporters (e.g., norepinephrine, serotonin, dopamine), measurement of G-protein coupling (e.g., GTP S binding or other assays), measurement of second messenger activity (e.g., adenylyl cyclase, cyclic AMP, phosphatidylinositol hydrolysis, and arachidonic acid), and high throughput patch clamp assays for ion channels. Assay formats to assess allosteric modulation or compounds exhibiting functional selectivity for specific signaling pathways (e.g., G-protein, beta arrestin) shall also be provided for high priority targets. Samples shall be tested in duplicate in at least six concentrations.

(2) The Contractor shall provide a graph containing the individual dose-response curves obtained for each sample in a given assay and the standard reference compound(s) plotted as log drug concentration on the abscissa and % activity on the ordinate. Data shall be summarized in terms of key pharmacologic parameters (e.g., EC50, IC50, Ki, KM, Vmax, and/or pA2 values) dependent upon the type of assay conducted. Mean + SEM or mean and confidence limits shall be determined from each value.

(3) The anticipated time frame for processing sample screening and data analysis is 4-8 weeks after receipt of the sample. Assay reports shall be prepared and sent to the COR

(electronically) and to the requesting investigator or provided via a secure web-based interface.

c. Assays to Assess ADMET Properties (e.g., Brain Penetrance, Bioavailability, and Cardiac Toxicity)

It is anticipated that approximately 1,500 of these assays may be requested per year.

The Contractor shall provide state-of-the-art, high-throughput screening to evaluate a subset of coded compounds per year, after approval by the COR, in one or more of the following assays:

(1) Bioavailability: Caco-2 cell assays to ascertain absorption and/or secretion of drugs/chemicals across the intestinal mucosa

(2) Model assays for blood brain barrier penetration (including efflux pumps, transporters and tight junctions). Efflux pump assays could include P-glycoprotein (P-gp) subtypes and multidrug resistance-associated proteins (MRPs).

(3) Predictive measures of Log P - hydrophobicity/lipophilicity

(4) Model assays to predict cardiac toxicity such as prolongation of the Q-T interval or human valvular interstitial cell assay (e.g., HERG, 5HT2B). Medium to high throughput patch clamp capabilities for hERG screening are highly desirable.

d. Development and Validation of New Assays

(1) The Contractor shall maintain a state-of-the-art knowledge of the field in order to update existing assays, establish binding assays for newly cloned human or rodent receptors and enzymes including orphan receptors, and establish new functional assays. For example, the Contractor shall have the capabilities to clone a newly discovered CNS receptor, maintain a stable transfected cell line expressing the receptor, and establish the binding and functional assays for the receptor in accordance with the standards established in the published scientific literature (i.e., KD, Bmax, degree of specific binding, radioligand, reference compounds, incubation conditions, etc.). It is anticipated that the Contractor will develop approximately 5-10 new assays per year. This may include the development of non-radioactive ligand binding technologies such as fluorescent-based assays, or assays utilizing other technologies, such as high throughput patch clamp electrophysiology to assess ion channel activity. Assay development may be at the request of the

COR and/or the Contractor may recommend novel targets for inclusion in the PDSP.

(2) The Contractor shall provide the COR with a timetable and estimate of the labor required to develop and validate each new assay prior to undertaking the work. Initiation of assay development will require written approval of the COR. The Contractor shall provide an update on the status of the assay (progress, obstacles encountered) in the monthly reports.

(3) The assays shall be reviewed and approved by the COR prior to inclusion in the NIMH

Psychoactive Drug Screening Program.

In the event that quality control/assurance issues arise with sample or reference compound data in any of the assays performed under the NIMH contract, the Contractor shall cooperate fully with the COR to resolve the issues, and if necessary, repeat assays in the specified tests at no additional costs. In the event that sample or reference compound quality control or assurance issues in a given assay cannot be resolved between the Contractor and COR, a scientific advisory group chosen by the COR shall be asked to review the data and make recommendations to resolve the issues.

5. Incorporation of Novel Techniques and Technologies

The Contractor is expected to maintain awareness of new tools, techniques, technologies, and approaches in areas applicable to this program. Novel technologies may be adopted and incorporated into the program as they are validated, upon approval by the COR.

6. Data Management and PDSP Ki Database

If required, the Contractor will receive transferred data gathered and derived for this specific requirement that will be used and stored in the database to fulfill services in the SOW under the resultant contract.

The Contractor shall develop and maintain two (2) electronic databases as follows:

a. The Contractor shall develop and maintain a secure, cumulative electronic Assay Results Database. This database shall be web-accessible, allowing investigator access to data associated with their samples and

COR access to all project data. The database shall contain binding, enzyme activity, and functional activity profiles of samples and reference compounds. The database shall be updated as new samples are received or new results obtained. The data shall be disclosed only to the COR and to the investigator or party supplying the sample or composition of matter. After contract expiration, all data gathered and derived during the performance period(s) and stored in the database, shall be exported and transferred to NIMH and/or any new contract.

b. The C Binding Affinity (Ki) Database, a searchable database of over 95,000 binding affinities obtained from the literature and screening results. The database, currently maintained with MySQL (open source) software on a Linux (Unix based) server using PHP (hypertext preprocessor) language, shall be maintained in the public domain and shall be accessible to queries through the contractor-designed and maintained website for the program The Contractor shall update the database on a regular basis with new data obtained from the literature and from screening results.

7. Outreach and Communication

a. The Contractor shall design, host, and maintain pages on the web with the following information:

Description of the NIMH Psychoactive Drug Screening Program

Procedures for submitting samples for screening

List of available assays, descriptions of assay conditions and/or assay protocols; and

Sample information and handling form.

Secure access to the Assay Results Database

Access to the Binding Affinity (Ki) Database

b. The Contractor shall make information available about the NIMH Psychoactive Drug Screening

Program at scientific meetings (e.g., the Society for Neuroscience annual meeting), as requested by the COR.

c. The Contractor shall provide technical advice and assistance to NIMH PDSP requestors, as needed.

This may include advice on appropriate assays based on known information on the sample to be tested and the goals of the project and/or assistance in interpretation of assay results.

8. Reporting Requirements

a. Assay Reports

(1) Assay reports shall be made available to the submitting investigator and the COR electronically via the online project database (see above Management and PDSP Ki Database) within one week of completion of testing.

(2) Each assay report shall include: the sample receipt date, investigator name and affiliation, sample information, tests requested and approved, batch number and dates on which tests were run, raw data from completed assays, and analysis of sample data (data shall be in graphic format with calculated values and SEM).

(3) The pharmacological significance of the sample data and/or recommendations for further testing of the sample shall be included in the report.

b. Quarterly Reports

(1) Quarterly reports shall be submitted to the CO and COR electronically in Microsoft Excel or

Microsoft Word format for PCs (the most recent version released or that has been released within the

18 months prior to the period for which the report is submitted) or comparable programs that are compatible with NIMH systems, within seven (7) calendar days after the end of each contract quarter.

Note to Offerors: Offerors should detail the electronic format used in their organization.

(2) The report shall include:

a. A summary of the number and type of samples (synthetic chemicals, natural products, PET/SPECT ligands, etc.) received over the course of the quarter;

b. An analysis of requests received including requestor type (e.g., academic/small business, NIH funding source) and compound characteristics (e.g., type (research tool, imaging ligand, therapeutic), target(s), therapeutic indication (where relevant)).

c. Statistics on assay completion (e.g, percentage of approved primary, secondary, and functional assays completed) and average timelines for assay completion.;

d. Clear documentation of unsuccessful efforts in sample screening in any pharmacological or functional assay and actions taken;

e. Summary of any new assays developed and validated under the contract;

f. References for any scientific publications that result from screening data generated under the contract;

g. A listing of requesting investigators, their institution and funding source, and the type of request (e.g., imaging ligand development, therapeutics development, library profiling, etc.); and

h. An update on the status of the PDSP Ki database and web server statistics on the databases

(e.g., the number of requests, amount of data transferred, etc).

d. Annual Reports

(1) Annual reports shall be submitted to the CO and COR electronically in Microsoft Excel or

Microsoft Word format for PCs (the most recent versions released or that have been released within the

18 months prior to the period for which the report is submitted) or comparable programs that are compatible with NIMH systems, within fourteen (14) calendar days after the expiration of each contract performance period.

(2) The annual report shall be compiled to summarize the information contained in that year's quarterly reports.

(3) The report shall include:

a. The cumulative chronological log of sample receipt, handling, and storage conditions and electronic database of investigators who have had samples screened under the contract, including each investigator's, affiliation, phone, fax, and e-mail address, and funding source.

b. The cumulative up-to-date electronic database of all samples and reference compounds screened in the pharmacological and functional assays.

c. An update on the status of the PDSP Ki database and web server statistics on the databases

(e.g., the number of requests, amount of data transferred, etc).

d. Summary data on numbers of assays (binding, secondary, functional) performed, project type (therapeutics, imaging ligand, probe), primary target, and therapeutic indication.

e. List of publications from that contract year citing PDSP data.

f. Summary of key findings supported by PDSP data.

e. Final Report

(1) The final report shall be submitted in place of the annual report for the final year.

(2) The final report shall be submitted to the CO and COR electronically in Microsoft Excel or

Microsoft Word format for PCs (the most recent versions released or that have been released within the

18 months prior to the period for which the report is submitted) or comparable programs that are compatible with NIMH systems, on or before the contract expiration date.

(3) The final report shall include an executive summary of all of the sample screening, assay development and validation activities conducted under the contract and an up-to-date protocol book of all pharmacological and functional assays available in the NIMH Psychoactive Drug Screening

Program.

f. Transition Plan - Transition to a subsequent Contractor or to the Government

(1) A transition plan will be delivered upon request at any time during the contract. The Contractor shall provide an updated Transition Plan and budget to the Contracting Officer and the COR with a list of all data programs and data files generated under the contract and all other Government property. The

Transition Plan shall describe the approach to providing all such data and the up-to-date protocols for all pharmacological and functional assays used in the NIMH Psychoactive Drug Screening Program to a successor Contractor or to the Government.

(2) The Contractor shall fully cooperate with any successor (e.g. Contractor and/or Government) to ensure the efficient transfer of all such data and Government property.

C. Estimated Recurring Workload

1. Base Year

a. After contract award, the Contractor shall:

(1) work on establishing and validating additional pharmacological and functional assays, as requested by the COR, to update the NIMH list of pharmacological and functional screening assays; and

(2) begin receiving and processing samples/compounds and updating/ maintaining the databases.

b. The annual assay workload is estimated as follows:

35,000 primary pharmacologic assays 10,000 secondary pharmacologic assays 125,000 functional assays 1,500 ADMET assays 5-10 new assays developed and validated

2. Options Years 1-4

During each subsequent year (if an option year is exercised) the Contractor shall provide on-going screening services similar to those provided during the base year. However, to potentially meet an increased demand in services, the Contractor must have the capability of expanding their throughput to meet a higher assay volume (e.g., up to 25% per subsequent year) greater than the base services specified in this SOW.

Option 1: Fee-For-Service

In addition to providing screening at no cost to requesting investigators, the contractor shall have the ability to conduct screening on a fee-for-service basis, if requested by the government. Prices for the services provided shall be set based on full or partial recovery of actual costs.

Option 2: Option for Increased Quantities

As demand for contract services may vary, the Contractor shall maintain the capability of expanding throughput to meet a higher assay volume. Each option for increased quantities may be exercised multiple times within a performance period. to fund a higher volume of screening. Each option for additional quantities may be exercised for up to 5% of the estimated annual assay workload, but not exceeding the ceiling of 25% per performance period.

APPENDIX 1

TITLE: NIMH PSYCHOACTIVE DRUG SCREENING PROGRAM (PDSP)

NIMH Pharmacological Assays of Interest1 (see Task 2b)

Receptor Class

Subtypes

Serotonin

5-HT1A, 5-HT1B, 5-HT1D , , 5-HT1E, 5-HT1F,

5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A,

5-HT6, 5-HT7

Dopamine D1, D2, D3, D4, D5

Glutamate NMDA agonist site, glycine site, PCP site, AMPA, Kainate, NR1, NR2b

Glutamate, metabotropic mGluRs 1-8

GABA GABA-A subtypes, GABA-B

Transporters SERT, NET, DAT, glutamate (EAAT1), glycine (GLYT2), GABA (GAT-1, -3), VMAT-1, VMAT-2

Adrenergic alpha1a, alpha1b; alpha2A, B, C; beta 1, 2, 3

Muscarinic M1, M2, M3, M4, M5

Nicotinic a2b2, a2b4, a3b2, a3b4, a4b2, a7

Opioid mu, delta, kappa, NOP

1 It is anticipated that >85% of samples shall be evaluated in human receptor binding assays.

Samples will also be evaluated in rodent (rat, mouse) receptor binding assays.

Sigma Sigma 1, 2

Histamine H1, H2, H3

Adenosine A1, A2A, A2B, A3

Purinergic receptors P2Y1, 2, 6, 4, 11, 12

Orphan GPCRs GPR40, 41, 43

Trace amine receptors

Melanocortin receptors MC1-5

Corticotropin-releasing factor CRFR1, CRFR2

Galanin

GAL1,2,3

Ion Channels hERG, Ca, Na

Neuropeptide NPY1-6, NPS

Cannabinoid

CB1, CB2

Neurokinin NK1, 2, 3

Chemokine CCR1-10, CXCR1-6, CCRL1-2

Oxytocin, Vasopressin OT, V1a,1b, 2, 3