Olutasidenib (FT-2102) is a highly potent and selective, orally active, brain penetrant mutant Isocitrate dehydrogenase 1 (IDH1) inhibitor, with IC50 values of 21.2 nM and 114 nM for IDH1- R132H and IDH1- R132C, respectively. Olutasidenib potently inhibits 2-HG production by multiple IDH1-R132 mutants (R132H, R132C, R132G, R132L), suggesting olutasidenib could be efficacious against most IDH1-R132 mutant-expressing tumors. Olutasidenib is highly selective for IDH1 isoforms, showing no appreciable inhibition against wild-type IDH1 and IDH2 mutants.
In vivo, Olutasidenib (12.5, 25, and 50 mg/kg; oral) in 12-hour intervals exhibits potent anti-tumor activity in HCT116-IDH1-R132H/+ xenograft bearing female BALB/c Nude mice. Olutasidenib has good cell permeability and low efflux ratio in the male CD-1 mouse, which indicate a low probability of p-glycoprotein driven efflux.
| Molecular Weight | 354.79 |
| Formula | C18H15ClN4O2 |
| CAS Number | 1887014-12-1 |
| Solubility (25°C) | DMSO 80 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related Isocitrate Dehydrogenase (IDH) Products |
|---|
| Mutant IDH1-IN-4
Mutant IDH1-IN-4 is an inhibitor of mutant isocitrate dehydrogenase 1 (IDH 1) with an IC50 value of ≤ 0.5 μM for mutant IDH 1 in R132H, HT1080 and U87R132H cells. |
| (S,S)-GSK321
(S,S)-GSK321 is the (S,S)-enantiomer of GSK321.GSK321 is a potent inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. |
| IDH1 Inhibitor 1
IDH1 Inhibitor 1 is a potent, orally bioavailable, brain-permeable, selective mutant IDH1 inhibitor that inhibits IDH1R132H, IDH1R132C, and IDH1WT with IC50s of 0.021 μM, 0.045 μM, and 2.52 μM, respectively. possesses antitumor activity. |
| IDH1 Inhibitor 7
IDH1 Inhibitor 7 is an IDH1 inhibitor with an IC50 of less than 100 nM. |
| (R,R)-GSK321
(R,R)-GSK321 is an isomer of GSK321 and a wild-type isocitrate dehydrogenase 1 (WT IDH1) inhibitor with an IC50 value of 120 nM. |
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