Chemical Probes logo
IHMT-IDH1-053 | IHMT-IDH1-053 : Covalent Inhibitor of IDH1
RATINGS:
Cellular Use: (4 reviews)

In Model Organisms: (4 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
Download

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
IDH1 (Mutant:R132H)
  • IC50:4.7 nM
  • Ki:37 nM
  • IC50:28 nM
  • Activity:~15% @ 72h at 10 µM
up to 10 uM

Selectivity

In Vitro Selectivity Assessment
Potency Assay Off-Target:
Specificity of IDH1-053 against wild-type (WT) and mutant IDH1/2 was assessed in a biochemical assay ...
Selectivity Assessment Description:
IDH1-053 exhibited specific activities against mutant IDH1 including R132H and R132C over IDH1 WT an ...

Potency
Cellular
In Vitro

IDH1 (Mutant:R132H)

Mode of Action: Covalent Inhibitor

Structure-Activity-Relationship data available? No

DOI Reference: 10.1016/j.ejmech.2023.115411

In Vivo Validations

Rat
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 0.16 ± 0.02 h
Systemic clearance: 23996 ± 6795 mL/h/Kg
Cmax: 199.67 ± 105.26 ng/mL
Tmax: 0.03 ± 0.00 h
Area Under the Curve:: 267.61 ± 12.02 h*ng/mL
Volume of Distribution at Steady-State: 5391 ± 1028 L/Kg

DOI Reference: 10.1016/j.ejmech.2023.115411

Dose: 10 mg/Kg
Route of delivery: Oral
Plasma half life: 0.30 ± 0.09 h
Systemic clearance: 260239 ± 81419 mL/h/Kg
Cmax: 88.13 ± 46.67 ng/mL
Tmax: 0.25 ± 0.00 h
Area Under the Curve:: 36.31 ± 12.31 h*ng/mL
Bioavailability: 9.26 ± 0.02%
Volume of Distribution at Steady-State: 118878 ± 69773 mL/Kg

DOI Reference: 10.1016/j.ejmech.2023.115411

Negative Control Compounds

cpd 17
Notes: cpd 17 binds reversably with IC50s 143 ± 6.9 nM and 1472 nM in biochemical and cellular assays respectively.

Chemical Information

Molecular Formula C25H33FN6O4S
SMILEs C=CS(=O)(=O)NC1CCN(c2ccc([C@H](C)Nc3ncc(F)c(N4C(=O)OC[C@@H]4C(C)C)n3)cc2)CC1
InChI InChI=1S/C25H33FN6O4S/c1-5-37(34,35)30-19-10-12-31(13-11-19)20-8-6-18(7-9-20)17(4)28-24-27-14-21(26)23(29-24)32-22(16(2)3)15-36-25(32)33/h5-9,14,16-17,19,22,30H,1,10-13,15H2,2-4H3,(H,27,28,29)/t17-,22+/m0/s1
Molecular weight 532.23 Da
AlogP 3.801700000000003
HBond acceptors 10
HBond donors 2
Atoms 70
PAINS * Yes

* This is an automated alert only, and may not necessarily indicate an issue with this probe. ( Learn more about PAINS )

References

Publications

Cross References

ChEMBL BindingDB PubChem canSAR

Expert Reviews

by SERP
(on 7 Jul 2026)
Cellular Use Rating
In Model Organisms
This is an IDH1 R132 mutant selective probe with cellular efficacy that was validated in vivo in a HT1080 xenograft mouse model. Of note, PK was performed in rats, however, PD was evaluated by testing...
by SERP+
(on 9 Jul 2026)
Cellular Use Rating
In Model Organisms
Overall this is a covalent (Cysteine 269 binding) chemical probe with selectivity against IDH1 R132 Arginine mutant over both the wild type IDH1, IDH2 and their respective mutants. The compound is well...
by SERP
(on 15 Aug 2026)
Cellular Use Rating
In Model Organisms
IHMT-IDH1-053 is a potent, covalent inhibitor of mutant IDH1. It is highly selective for mutant IDH1 versus wildtype IDH1 and mutant/wildtype IDH2, although proteome-wide reactivity has not been assessed....
by SERP
(on 25 Aug 2026)
Cellular Use Rating
In Model Organisms
Selectivity over IDH1-WT and IDH2 WT/mutant proteins has been demonstrated, but broader selectivity profiling is lacking. In-cell target engagement has not been reported, and the reactivity of this covalent...
If you wish to explore AI-generated evaluations, please visit the page on our collaborator Compound VALET.
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