DHODH-IN-21

DHODH-IN-21 (compound 19) is an orally active selective dihydroorotate dehydrogenase (DHODH) inhibitor with an IC50 value of 1.1 nM. DHODH-IN-21 has anticancer activity and can be used in studies of acute myeloid leukaemia (AML)[1].

Research Areas >> Cancer

Mouse DHODH:140 nM (IC50)

Rat DHODH:1580 nM (IC50)

Dog DHODH:8.5 nM (IC50)

Monkey DHODH:1.6 nM (IC50)

DHODH-IN-21 (compound 19) inhibits the proliferation of MOLM-13 and THP-1 cells with the IC50 values of 2.0 nM and 5.0 nM, respectively[1].

DHODH-IN-21 (compound 19) (p.o., 10 or 20 mg/kg, everyday, 5 days) inhibits tumor growth in a dose-dependent manner but no effect on body weight in female NSG mice[1]. Animal Model: Human MOLM-13 AML xenograft model in female NSG mice[1] Dosage: 10, 20 mg/kg Administration: Oral administration; everyday; 5 days Result: Inhibited tumor volume size by 44% and 60% at 10 mg/kg and 20 mg/kg respectively. Animal Model: Mouse, rat[1] Dosage: Administration: 2 mg/kg i.v. or 10 mg/kg p.o. Result: The pharmacokinetic parameters of DHODH-IN-21 (compound 19) Parameter Mouse Rat CL (mL/min/kg) 11 32 Vdss (L/kg) 1.3 2.3 t1/2(h) 2.3 2.0 Cmax (ng/mL) 4047 1713 tmax(h) 0.42 1.7 AUC0→inf(h•ng/mL) 16,066 9214 F% 103 167

[1]. Justin S Cisar, et al. N-Heterocyclic 3-Pyridyl Carboxamide Inhibitors of DHODH for the Treatment of Acute Myelogenous Leukemia. J Med Chem. 2022 Aug 4.