This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only.

Background: The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) was officially established in fiscal year 2012 to transform the translational science process so that new treatments and cures for disease can be delivered to patients faster. NCATS, one of 27 Institutes and Centers (ICs) at NIH, strives to develop innovations to reduce, remove or bypass costly and time-consuming bottlenecks in the translational research pipeline in an effort to speed the delivery of new drugs, diagnostics and medical devices to patients.

Prior work at NCATS has produced a series of small molecule IRAK4 / FLT3 kinase dual inhibitors, including NCGC00371481 and its structural analogs. Compounds such as ‘1481 have shown promising results in cellular and mouse models of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Further optimization of the biochemical, physiochemical and pharmacokinetic properties of these compounds is required, and may eventually produce a clinical candidate that could be used to treat cancers such as MDS and / or AML.

On a separate but related program, prior work at NCATS has led to the discovery of novel small molecule inhibitors of the kinase enzymes LATS1 and LATS2. Inhibitors of these targets may be useful in wound healing, tissue regeneration, and other related areas.

In order to fully assess and optimize the biological properties of compounds on these two programs, NCATS needs to understand not only their ‘on-target activity' (that is, their inhibition of the desired targets mentioned above), but also their ‘off-target activity', meaning any undesired activity at other biological targets. In particular, NCATS needs to understand if they have significant activity at off-targets that are important for safety. By monitoring potential activity at these targets in vitro, NCATS can predict the occurrence of safety-related adverse events that might occur once compounds are advanced into clinical testing. This data will thus help NCATS to identify and ultimately optimize out any unwanted activity, thus allowing NCATS to prioritize the safest compounds for advancement into the clinic.

Testing of five (5) small molecule compounds against a broad panel of 174 safety-related targets will allow NCATS to prioritize safer compounds for ultimate advancement into human clinical trials.

Purpose and Objectives: The purpose of this acquisition is the testing of five (5) novel small molecule compounds in a broad panel of 174 safety-related biological targets. Such testing will inform on the activity of these compounds at critical, safety-related biological targets, and will help predict safety-related adverse events that might occur as compounds are advanced into the clinic.

Project Requirements: Responses must demonstrate capability of meeting the following requirements:

1. Perform experiments using established binding assays testing each of five (5) small molecule compounds for activity against at least 174 safety-related targets, including all of the following GPCR, enzyme and ion channel targets:

A1 Human Adenosine GPCR Binding (Antagonist Radioligand) Assay
A2A Human Adenosine GPCR Binding (Agonist Radioligand) Assay
A2B Human Adenosine GPCR Binding (Antagonist Radioligand) Assay
A3 Human Adenosine GPCR Binding (Agonist Radioligand) Assay
Adenosine Guinea Pig Transporter Binding (Antagonist Radioligand) Assay
alpha1A Rat Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
alpha1B Rat Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
alpha1D Human Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
alpha2A Human Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
alpha2B Human Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
alpha2C Human Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
beta1 Human Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
beta2 Human Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
beta3 Human Adrenoceptor GPCR Binding (Antagonist Radioligand) Assay
NET Human Norepinephrine Transporter Binding (Antagonist Radioligand) Assay
MCR Human Aldosterone NHR Binding (Agonist Radioligand) Assay
AR Human Androgen NHR Binding (Agonist Radioligand) Assay
AT1 Human Angiotensin GPCR Binding (Agonist Radioligand) Assay
AT2 Human Angiotensin GPCR Binding (Agonist Radioligand) Assay
APJ Human Apelin GPCR Binding (Agonist Radioligand) Assay
Atrial Natriuretic Factor (ANF, Non-Selective) Guinea Pig Binding Assay
BB1 Human Bombesin GPCR Binding (Agonist Radioligand) Assay
BB2 Human Bombesin GPCR Binding (Agonist Radioligand) Assay
BB3 Human Bombesin GPCR Binding (Agonist Radioligand) Assay
B1 Human Bradykinin GPCR Binding (Agonist Radioligand) Assay
B2 Human Bradykinin GPCR Binding (Agonist Radioligand) Assay
CGRP (CLR/RAMP1) Human Calcitonin GPCR Binding (Agonist Radioligand) Assay
Cav1.2 (L-type) Rat Calcium Ion Channel Binding (Diltiazem Site) Assay
Cav1.2 (L-type) Rat Calcium Ion Channel Binding (Dihydropyridine Site) Assay
Cav1.2 (L-type) Rat Calcium Ion Channel Binding (Verapamil Site) Assay
Cav2.2 (N-type) Rat Calcium Ion Channel Binding (Antagonist Radioligand) Assay
CB1 Human Cannabinoid GPCR Binding (Antagonist Radioligand) Assay
CB2 Human Cannabinoid GPCR Binding (Agonist Radioligand) Assay
CCR1 Human Chemokine GPCR Binding (Agonist Radioligand) Assay
CCR2 Human Chemokine GPCR Binding (Agonist Radioligand) Assay
CCR5 Rhesus Macaque Chemokine GPCR Binding (Agonist Radioligand) Assay
CCK1 (CCKA) Human Cholecystokinin GPCR Binding (Antagonist Radioligand) Assay
CCK2 (CCKB) Human Cholecystokinin GPCR Binding (Agonist Radioligand) Assay
CHT1 Rat Choline Transporter Binding (Antagonist Radioligand) Assay
Rat Tubulin [3H] Colchicine Binding Assay
CRF1 Human Corticotropin-Releasing Factor GPCR Binding (Agonist Radioligand) Assay
D1 Human Dopamine GPCR Binding (Antagonist Radioligand) Assay
D2S Human Dopamine GPCR Binding (Antagonist Radioligand) Assay
D3 Human Dopamine GPCR Binding (Antagonist Radioligand) Assay
D4.2 Human Dopamine GPCR Binding (Antagonist Radioligand) Assay
D5 Human Dopamine GPCR Binding (Antagonist Radioligand) Assay
DAT Human Dopamine Transporter Binding (Antagonist Radioligand) Assay
ETA Human Endothelin GPCR Binding (Agonist Radioligand) Assay
ETB Human Endothelin GPCR Binding (Agonist Radioligand) Assay
EGFR Human RTK Kinase Binding (Agonist Radioligand) Assay
ERalpha Human Estrogen NHR Binding (Agonist Radioligand) Assay
ERbeta Human Estrogen NHR Binding (Agonist Radioligand) Assay
GABA (Non-Selective) Rat Transporter Binding (Antagonist Radioligand) Assay
Non-Selective Rat GABAA Ion Channel [3H] Muscimol Binding (Agonist Radioligand) Assay
Non-Selective Rat GABAA Ion Channel [3H] Flunitrazepam Binding (Agonist Radioligand) Assay
Non-Selective Rat GABAA Ion Channel [3H] TBOB Binding (Antagonist Radioligand) Assay
GABAB (B1a/B2) Human GABAB GPCR Binding (Antagonist Radioligand) Assay
GABAB (B1b/B2) Human GABAB GPCR Binding (Antagonist Radioligand) Assay
Rat Cortex [3H] Gabapentin Binding Assay
GHB Rat Binding (Antagonist Radioligand) Assay
Glucagon Human Glucagon GPCR Binding (Agonist Radioligand) Assay
GR Human Glucocorticoid NHR Binding (Agonist Radioligand) Assay
Glutamate (AMPA, Non-Selective) Rat Ion Channel [3H] AMPA Binding Assay
Glutamate, Kainate
Glutamate (NMDA, Non-Selective) Rat Ion Channel [3H] CGP-39653 Binding Assay
Glutamate, NMDA, Glycine [3H] MDL 105,519 Binding Assay
Glutamate (Non-Selective) Rat Ion Channel [3H] TCP Binding Assay
Glutamate (NMDA, Non-Selective) Rat Ion Channel [3H] Ifenprodil Binding Assay
mGlu2 Human Glutamate (Metabotropic) GPCR Binding (Antagonist Radioligand) Assay
mGlu5 Human Glutamate (Metabotropic) GPCR Binding (Agonist Radioligand) Assay
Non-Selective Rat Glycine Ion Channel [3H] Strychnine Binding Assay
GLYT1 Rat Glycine Transporter Binding (Antagonist Radioligand) Assay
GnRH Human Gonadotrophin-Releasing Hormone GPCR Binding (Agonist Radioligand) Assay
GHSR Human Ghrelin GPCR Binding (Agonist Radioligand) Assay
H1 Human Histamine GPCR Binding (Antagonist Radioligand) Assay
H2 Human Histamine GPCR Binding (Antagonist Radioligand) Assay
H3 Human Histamine GPCR Binding (Agonist Radioligand) Assay
Imidazoline I2, Central Rat Binding (Antagonist Radioligand) Assay
IP3R1 Rat IP3 Ion Channel Binding (Agonist Radioligand) Assay
IR Rat RTK Kinase Binding (Agonist Radioligand) Assay
Interleukin IL-1 R1
IL-6 Human Binding (Agonist Radioligand) Assay
CXCR2 (Non-Selective) Human Chemokine GPCR Binding (Agonist Radioligand) Assay
CXCR2 (IL-8RB) Human Chemokine GPCR Binding (Agonist Radioligand) Assay
CXCR3 Human Chemokine GPCR Binding (Agonist Radioligand) Assay
CXCR4 Human Chemokine GPCR Binding (Agonist Radioligand) Assay
CX3CR1 Human Chemokine GPCR Binding (Agonist Radioligand) Assay
CysLT1 Human Leukotriene GPCR Binding (Agonist Radioligand) Assay
BLT1 (LTB4) Human Leukotriene GPCR Binding (Agonist Radioligand) Assay
MCH1 Human Melanin-Conc. Hormone GPCR Binding (Agonist Radioligand) Assay
MC1 Human Melanocortin GPCR Binding (Agonist Radioligand) Assay
MC3 Human Melanocortin GPCR Binding (Agonist Radioligand) Assay
MC4 Human Melanocortin GPCR Binding (Agonist Radioligand) Assay
MC5 Human Melanocortin GPCR Binding (Agonist Radioligand) Assay
MT1 Human Melatonin GPCR Binding (Agonist Radioligand) Assay
MT2 Human Melatonin GPCR Binding (Agonist Radioligand) Assay
VMAT (Non-Selective) Human Vesicular Monoamine Transporter Binding Assay
Motilin Human Motilin GPCR Binding (Agonist Radioligand) Assay
M1 Human Acetylcholine (Muscarinic) GPCR Binding (Antagonist Radioligand) Assay
M2 Human Acetylcholine (Muscarinic) GPCR Binding (Antagonist Radioligand) Assay
M3 Human Acetylcholine (Muscarinic) GPCR Binding (Antagonist Radioligand) Assay
M4 Human Acetylcholine (Muscarinic) GPCR Binding (Antagonist Radioligand) Assay
M5 Human Acetylcholine (Muscarinic) GPCR Binding (Antagonist Radioligand) Assay
Non-Selective Rat Acetylcholine (Muscarinic) GPCR Binding (Agonist Radioligand) Assay
NK1 Human Tachykinin GPCR Binding (Agonist Radioligand) Assay
NK2 Human Tachykinin GPCR Binding (Antagonist Radioligand) Assay
NK3 Human Tachykinin GPCR Binding (Agonist Radioligand) Assay
Y1 Human Neuropeptide Y GPCR Binding (Agonist Radioligand) Assay
Y2 Human Neuropeptide Y GPCR Binding (Agonist Radioligand) Assay
NT1 Human Neurotensin GPCR Binding (Agonist Radioligand) Assay
nAChR Human Acetylcholine (Nicotinic) Ion Channel Binding Assay
nAChR (alpha7) Rat Ion Channel Binding (Antagonist Radioligand) Assay
nAChR (alpha7) Human Ion Channel [3H] Methyllycaconitine Binding Assay
nAChR (alpha1) Human Ion Channel Binding (Antagonist Radioligand) Assay
nAChR (alpha4/beta2) Rat Ion Channel Binding (Agonist Radioligand) Assay
delta (DOP) Human Opioid GPCR Binding (Antagonist Radioligand) Assay
kappa (KOP) Human Opioid GPCR Binding (Antagonist Radioligand) Assay
mu (MOP) Human Opioid GPCR Binding (Antagonist Radioligand) Assay
NOP (ORL1) Human Opioid GPCR Binding (Agonist Radioligand) Assay
OT Human Vasopressin / Oxytocin GPCR Binding (Agonist Radioligand) Assay
Phorbol Ester Binding Assay
PAF Human Platelet-Activating Factor GPCR Binding (Agonist Radioligand) Assay
PDGFR (Non-Selective) Mouse RTK Kinase Binding (Agonist Radioligand) Assay
KV (Non-Selective) Rat Potassium Ion Channel [125I] alpha-Dendrotoxin Binding Assay
KATP Hamster Potassium Ion Channel Binding (Antagonist Radioligand) Assay
SKCa (Non-Selective) Rat Potassium Ion Channel [125I] Apamin Binding Assay
hERG Human Potassium Ion Channel [3H] Astemizole Binding (Antagonist Radioligand) Assay
DP2 Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
DP1 Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
EP1 Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
EP2 Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
EP4 Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
FP Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
Non-Selective Rat P2Y GPCR Binding (Agonist Radioligand) Assay
RXRalpha Human Retinoid X NHR Binding (Agonist Radioligand) Assay
Non-Selective Rat PDE [3H] Rolipram Binding (Antagonist Radioligand) Assay
RY3 Rat Ryanodine Ion Channel Binding (Agonist Radioligand) Assay
5-HT1A Human Serotonin GPCR Binding (Agonist Radioligand) Assay
5-HT1B Rat Serotonin GPCR Binding (Antagonist Radioligand) Assay
5-HT2B Human Serotonin GPCR [3H]LSD Binding (Agonist Radioligand) Assay
5-HT2C Human Serotonin GPCR Binding (Antagonist Radioligand) Assay
5-HT3 Human Serotonin Ion Channel Binding (Antagonist Radioligand) Assay
5-HT4 Guinea Pig Serotonin GPCR Binding (Antagonist Radioligand) Assay
5-HT5A Human Serotonin GPCR Binding (Agonist Radioligand) Assay
5-HT6 Human Serotonin GPCR Binding (Agonist Radioligand) Assay
5-HT7 Human Serotonin GPCR Binding (Agonist Radioligand) Assay
SET Human Serotonin Transporter Binding (Antagonist Radioligand) Assay
sigma1 Human Binding (Antagonist Radioligand) Assay
sigma2 Rat [3H] Ifenprodil Binding (Agonist Radioligand) Assay
Non-Selective Rat Sodium Ion Channel [3H] Batrachotoxinin Binding (Site 2) Assay
sst1 Human Somatostatin GPCR Binding (Agonist Radioligand) Assay
sst3 Human Somatostatin GPCR Binding (Agonist Radioligand) Assay
sst2 Human Somatostatin GPCR Binding (Agonist Radioligand) Assay
sst4 Human Somatostatin GPCR Binding (Agonist Radioligand) Assay
sst5 Human Somatostatin GPCR Binding (Agonist Radioligand) Assay
TR (Non-Selective) Rat Thyroid Hormone NHR Binding (Agonist Radioligand) Assay
TRH Rat Thyrotropin-RH GPCR Binding (Agonist Radioligand) Assay
TGFbeta (Non-Selective) Mouse TKL Kinase Binding (Agonist Radioligand) Assay
UT (GPR14) Human Urotensin GPCR Binding (Agonist Radioligand) Assay
VIP1 (VPAC1) Human VIP and PACAP GPCR Binding (Agonist Radioligand) Assay
VIP2 (VPAC2) Human VIP and PACAP GPCR Binding (Agonist Radioligand) Assay
V1A Human Vasopressin / Oxytocin GPCR Binding (Antagonist Radioligand) Assay
V1B Human Vasopressin / Oxytocin GPCR Binding (Agonist Radioligand) Assay
V2 Human Vasopressin / Oxytocin GPCR Binding (Agonist Radioligand) Assay
VDR Human NHR Binding (Agonist Radioligand) Assay
OX2 Human Orexin GPCR Binding (Agonist Radioligand) Assay
CysLT2 Human Leukotriene GPCR Binding (Agonist Radioligand) Assay
IP Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
PR Human Progesterone NHR Binding (Agonist Radioligand) Assay
EP3 Human Prostanoid GPCR Binding (Agonist Radioligand) Assay
CT Human Calcitonin GPCR Binding (Agonist Radioligand) Assay
OX1 Human Orexin GPCR Binding (Agonist Radioligand) Assay
Histamine H4
Non-Selective Rat P2X Ion Channel Binding (Agonist Radioligand) Assay

2. Capable of testing the aforementioned five (5) compounds in all the assays described above in under three (3) months' time.

3. Provide a comprehensive report with the results of the single-dose duplicate testing of each of the 5 compounds against the 174 targets.

4. Capable of furnishing all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to complete this work.

5. Possess all critical instrumentation necessary for this work.

6. Possess significant experience (i.e. more than 5 years) in the testing of small molecule compounds for activity against the panel of 174 targets.

Anticipated Period of Performance: Within three (3) months from award date and receipt of first batch of material.

Other Important Considerations: Any data generated as a result of this work will be the property of NCATS.

Capability Statement / Information Sought: Respondents must provide clear and convincing evidence of possessing the knowedge, skills, abilities and experience to successfully perform the requirements described in this announcement. Detailed past experience in implementing similar requirements to the requirement described in this announcement must be clearly delineated in any response provided. Respondents must provide clear and convincing documentation of their capability in providing analytical quality control and any other requirements and services specified in this notice. Respondents must provide a general overview of the respondents' opinions about the difficulty and /or feasibility of the potential requirement, and any information regarding innovative ideas or concepts.

Respondents must also provide information in sufficient detail of the respondents' (a) staff expertise, including their availability, experience, and formal and other training; (b) current in-house capability and capacity to perform the work; (c) prior completed projects of similar nature; (d) corporate experience and management capability; and (e) examples of prior completed Government contracts, references, and other related information..

Respondents must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements.

One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2" x 11" paper size, with 1" top, bottom, left and right margins, and with single or double spacing. The response is limited to fifteen (15) pages; the 15-page limit does not include the cover page, executive summary, resumes, or references, if requested.

The response must include the respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses.

The response to this notice must be submitted electronically to the Contract Specialist and Contracting Officer. Facsimile responses are NOT accepted.

The response must reference the announcement number and be submitted electronically to Mark McNally, Contract Specialist, at [email protected], and copy Jeffrey Schmidt, Contracting Officer, at [email protected]. The response must be received by the response date and time specified in this announcement.

Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work.

Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation.

Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).