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MRTX849 | Covalent Inhibitor of KRAS (Mutant:G12C)
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 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
KRAS (Mutant:G12C)
  • Kobs:low uM
  • IC50:14 nM; 4.7 nM (24h)
Covalent Inhibitor
up to 100 nM
up to 500 nM

Selectivity

Potency
Cellular
In Vitro

KRAS (Mutant:G12C)

Mode of Action: Covalent Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.9b02052

In Vivo Validations

Mouse, Rat, Dog
Dose: 3 mg/Kg IV, 3 to 100 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 1.51 (M), 2.57 (R), 7.56 (D) h
Systemic clearance: 19.9 (M), 44.2 (R), 29.6 (D) ml/min/kg
Target engagement assay: Anti-tumor activity of MRTX849 was evaluated in a MIA PaCa-2 xenograft model.

DOI Reference: 10.1021/acs.jmedchem.9b02052

Negative Control Compounds

Compound-21

Orthogonal Probes def

ARS-1620
AMG-510

Chemical Information

Molecular Formula C32H35ClFN7O2
SMILEs C=C(F)C(=O)N1CCN(c2nc(OC[C@@H]3CCCN3C)nc3c2CCN(c2cccc4cccc(Cl)c24)C3)C[C@@H]1CC#N
InChI InChI=1S/C32H35ClFN7O2/c1-21(34)31(42)41-17-16-40(18-23(41)11-13-35)30-25-12-15-39(28-10-4-7-22-6-3-9-26(33)29(22)28)19-27(25)36-32(37-30)43-20-24-8-5-14-38(24)2/h3-4,6-7,9-10,23-24H,1,5,8,11-12,14-20H2,2H3/t23-,24-/m0/s1
Molecular weight 603.25 Da
AlogP 4.732980000000004
HBond acceptors 9
HBond donors --
Atoms 78

References

Publications

Cross References

canSARChEMBLBindingDB

Vendors

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Expert Reviews

by SERP
(on 25 Jul 2020 )
Cellular Use Rating
In Model Organisms
( The reviewer did not leave any comments )
by SERP
(on 4 Aug 2020 )
Cellular Use Rating
In Model Organisms
MRTX849 is a very potent and selective inhibitor of kRas G12C. Along with AMG-510 this compound is one of the first to proceed through clinical development showing benefit in certain tumor types that...
by SERP
(on 5 Sept 2020 )
Cellular Use Rating
In Model Organisms
MRTX849: - Is a potent, orally-available, and mutation-selective covalent inhibitor of KRAS G12C presently undergoing phaseI/II clinical trials in patients with non-small cell lung cancer. MRTX849...
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