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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

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
Allosteric
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

mice
Dose: 150 mg/kg
Route of delivery: Intraperitoneal
Organ of interest (O): bone marrow xenograft
Target engagement assay: Indirect: quantification of R-2HG levels

Reference: --

Negative Control Compounds

GSK990

Orthogonal Probes def

AGI-5198

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

References

Publications

Cross References

canSARChEMBLBindingDB

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)

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