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GSK864 | Allosteric of IDH1 (Mutant:R132C, R132H, R132G)
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

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Targets Biochemical/Biophysical Potency Cellular Potency
IDH1 (Mutant:R132C, R132H, R132G)
  • IC 50:15 nM R132H
  • IC 50:8.8 nM R132C
  • IC 50:16.6 nM R132G
  • EC 50:320 nM
50 nM - 1 uM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - wild-type IDH1 466.5 nM, R140Q IDH2 1916 nM, R172S IDH2 997 nM, wild-type IDH2 1360 nM

Potency
Cellular
In Vitro

IDH1 (Mutant:R132C, R132H, R132G)

Mode of Action: Allosteric

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/nchembio.1930

In Vivo Validations

Mouse
Dose: 213 mg/kg
Route of delivery: Intraperitoneal
Cmax: 5830 ng/mL
Area Under the Curve:: 52300 hr*ng/mL
Organ of interest (O): bone marrow xenograft
Target engagement assay: Indirect: quantification of R-2HG levels

DOI Reference: 10.1038/nchembio.1930

Negative Control Compounds

GSK990
Notes: GSK990, a structurally related inactive inhibitor, no inhibition after treatment up to 10 uM.

Orthogonal Probes def

AGI-5198
IDH-053

Chemical Information

Molecular Formula C30H31FN6O4
SMILEs COc1c(C)cc(NC(=O)c2nn(Cc3ccc(F)cc3)c3c2CN(C(=O)c2ccc[nH]2)C[C@]3(C)C(N)=O)cc1C
InChI InChI=1S/C30H31FN6O4/c1-17-12-21(13-18(2)25(17)41-4)34-27(38)24-22-15-36(28(39)23-6-5-11-33-23)16-30(3,29(32)40)26(22)37(35-24)14-19-7-9-20(31)10-8-19/h5-13,33H,14-16H2,1-4H3,(H2,32,40)(H,34,38)/t30-/m0/s1
Molecular weight 558.24 Da
AlogP 3.675340000000002
HBond acceptors 10
HBond donors 4
Atoms 72

Vendors

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Expert Reviews

by SERP
(on 29 May 2016)
Cellular Use Rating
In Model Organisms
This small molecule and its inactive analog, GSK990, are early-stage probe candidates for studying the inhibition of mutant IDH1 in cancer. Further biochemical profiling needs to be completed to better...
by SERP
(on 10 Sept 2016)
Cellular Use Rating
In Model Organisms
The selectivity of GSK864 for IDH1 was illustrated by conducting a chemoproteomics experiment with a closely related analog, GSK321 [PMID: 26436839]. GSK321 was functionalized so that it could be immobilized...
GSK864 is an allosteric inhibitor of mutant IDH1, with moderate selectivity versus wild-type IDH1 and IDH2. GSK864 dose-dependently reduces levels of intracellular levels of 2-HG both in vitro and in...

Portal Comments

In a 2023 study, Hu et al. evaluated GSK-864 in live-cell assays for Phospholipidosis induction, cautioning about adverse effects at concentrations near 1 uM. (DOI:10.1016/j.chembiol.2023.09.003)

(last updated: 7 Nov 2023)

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