| Identification | Back Directory | [Name]
3-Pyridinecarboxamide, N-(2-chloro-4-methyl-3-pyridinyl)-6-[4-ethyl-4,5-dihydro-3-(hydroxymethyl)-5-oxo-1H-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]- | [CAS]
2450341-39-4 | [Synonyms]
DHODH-IN-21
3-Pyridinecarboxamide, N-(2-chloro-4-methyl-3-pyridinyl)-6-[4-ethyl-4,5-dihydro-3-(hydroxymethyl)-5-oxo-1H-1,2,4-triazol-1-yl]-5-fluoro-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]- | [Molecular Formula]
C20H19ClF4N6O4 | [MOL File]
2450341-39-4.mol | [Molecular Weight]
518.85 |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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 | |
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| [IC 50]
Mouse DHODH: 140 nM (IC50); Rat DHODH: 1580 nM (IC50); Dog DHODH: 8.5 nM (IC50); Monkey DHODH: 1.6 nM (IC50) | [References]
[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. DOI:10.1021/acs.jmedchem.2c00788 |
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