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AMG-510 | AMG-510 : Covalent, G12C mutant specific inhibitor of KRAS
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)
  • kinact/KI:9900 ± 1800 M–1 s–1
  • IC 50:68 nM
Covalent Inhibitor
500 nM
Up to 1 uM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
Cysteine-proteome profiling
Selectivity Assessment Description:
Cysteine-proteome profiling (MS) further revealed (R)-38 to be highly selective for covalent modi ...

Potency
Cellular
In Vitro

KRAS (Mutant:G12C)

Mode of Action: Covalent Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.9b01180

In Vivo Validations

Mouse, Rat, Dog
Dose: 1 mg/Kg IV, 10 mg/Kg PO, Reviewer suggest 30 and 100 mg/Kg PO
Route of delivery: Intravenous, Oral
Plasma half life: 0.5 (M), 0.5 (R), 0.4 (D) h
Systemic clearance: 1.6 (M) 3.4 (R), 2.2 (D) L/h/kg

Reference: --

Negative Control Compounds

Compound-8

Orthogonal Probes def

ARS-1620
MRTX849

Chemical Information

Molecular Formula C30H30F2N6O3
SMILEs C=CC(=O)N1CCN(c2nc(=O)n(-c3c(C)ccnc3C(C)C)c3nc(-c4c(O)cccc4F)c(F)cc23)[C@@H](C)C1
InChI InChI=1S/C30H30F2N6O3/c1-6-23(40)36-12-13-37(18(5)15-36)28-19-14-21(32)26(24-20(31)8-7-9-22(24)39)34-29(19)38(30(41)35-28)27-17(4)10-11-33-25(27)16(2)3/h6-11,14,16,18,39H,1,12-13,15H2,2-5H3/t18-/m0/s1
Molecular weight 560.23 Da
AlogP 4.4814200000000035
HBond acceptors 9
HBond donors 1
Atoms 71

References

Publications

Cross References

canSARChEMBLBindingDBPubMed

Vendors

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Expert Reviews

by SERP
(on 30 Jul 2020 )
Cellular Use Rating
In Model Organisms
AMG-510 is the potent R-atropisomer [t1/2 (Racemization) >180 years at 25 °C, ΔG⧧rotation > 31 kcal/mol]. The non-specific reactivity of AMG 510 with GSH is relatively slow (t1/2 = 196 min/within...
by SERP
(on 30 Jul 2020 )
Cellular Use Rating
In Model Organisms
AMG 510 (compound 38) is a potent and selective covalent inhibitor of KRASG12C. It was derived by SAR and pharmacological optimisation of a series of compounds built upon the principle of covalently...
by SERP
(on 13 Aug 2020 )
Cellular Use Rating
In Model Organisms
AMG-510 is a covalent inhibitor of KRASG12C, specifically targeting the mutant cysteine-12 residue. It is created by leveraging the ARS-1620 structure and the exploitation of the cryptic pocket with...
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria