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MK-3697 | MK-3697 : Antagonist of HCRTR2
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
HCRTR2
  • Ki:1.1 nM
  • IC50:16 nM
Antagonist
100 nM due to potential off-target effects
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
Selective again OX1 both in vitro and in cells (Ki = 31 µM and IC50 > 10 µM, respectively)

Potency
Cellular
In Vitro

HCRTR2

Mode of Action: Antagonist

Structure-Activity-Relationship data available? No

DOI Reference: 10.1016/j.bmcl.2014.08.041

In Vivo Validations

Rat
Dose: 2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 0.4 ± 0.0 h
Systemic clearance: 40.7 ± 5.1 mL/min/Kg
Volume of Distribution at Steady-State: 1.2 ± 0.1 L/Kg

DOI Reference: 10.1016/j.bmcl.2014.08.041

Dose: 5 mg/Kg
Route of delivery: Oral
Cmax: 2.1 ± 0.5 uM
Tmax: 0.3 ± 0.1 h
Area Under the Curve:: 3.0 ± 0.8 uM*h
Bioavailability: 64 ± 18%

DOI Reference: 10.1016/j.bmcl.2014.08.041

Dose: 15 mg/Kg
Route of delivery: Oral
Cmax: 5.3 µM
Tmax: 0.8 h
Area Under the Curve:: 17.2 µMh
Bioavailability: 83.6 %
Target engagement assay: unbound plasma concentration: 0.90 µM

DOI Reference: 10.1016/j.bmcl.2014.08.041

Dog
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 1.2 ± 0.1 h
Systemic clearance: 7.2 ± 2.5 mL/min/kg
Volume of Distribution at Steady-State: 0.7 ± 0.1 L/Kg

DOI Reference: 10.1016/j.bmcl.2014.08.041

Dose: 3 mg/Kg
Route of delivery: Oral
Cmax: 2.1 ± 0.5 uM
Tmax: 0.7 ± 0.3 h
Area Under the Curve:: 7.5 ± 3.5 uM*h
Bioavailability: 49 ± 14%

DOI Reference: 10.1016/j.bmcl.2014.08.041

Dose: 3 mg/Kg
Route of delivery: Oral
Cmax: 2.7 µM
Tmax: 1.0 h
Fb : 83.1 %
Target engagement assay: unbound plasma concentration: 0.46 µM

DOI Reference: 10.1016/j.bmcl.2014.08.041

Mouse
Dose: 100 mg/Kg
Route of delivery: Oral
Cmax: 55.3 µM
Tmax: 2.0 h
Target engagement assay: unbound plasma concentration: 4.9 μM

DOI Reference: 10.1016/j.bmcl.2014.08.041

Chemical Information

Molecular Formula C23H21N5O3S
SMILEs COc1ccc(CNC(=O)c2cc(-c3cncc(C)c3)ncc2-c2nccs2)nc1OC
InChI InChI=1S/C23H21N5O3S/c1-14-8-15(11-24-10-14)19-9-17(18(13-26-19)23-25-6-7-32-23)21(29)27-12-16-4-5-20(30-2)22(28-16)31-3/h4-11,13H,12H2,1-3H3,(H,27,29)
Molecular weight 447.14 Da
AlogP 0.0
HBond acceptors 8
HBond donors 1
Atoms 53

References

Publications

Cross References

canSARChEMBLBindingDB

Vendors

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Expert Reviews

by SERP
(on 4 Jan 2024 )
Cellular Use Rating
In Model Organisms
( The reviewer did not leave any comments )
by SERP+
(on 14 Oct 2025 )
Cellular Use Rating
In Model Organisms
MK-3697 is a good chemical probe/antagonist for hypocretin (orexin) receptor 2 for cellular and in-vivo use. The recommended dose, however, should be lower than 1µM because of potential off-target effects....
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