| Identification | Back Directory | [Name]
2-Propenamide, 3-[4-[[(3-fluoro-5,7,8,13,13b,14-hexahydro-14-methyl-5-oxoindolo[2',3':3,4]pyrido[2,1-b]quinazolin-10-yl)oxy]methyl]phenyl]-N-hydroxy-, (2E)- | [CAS]
2411379-14-9 | [Synonyms]
HDAC/Top-IN-1
2-Propenamide, 3-[4-[[(3-fluoro-5,7,8,13,13b,14-hexahydro-14-methyl-5-oxoindolo[2',3':3,4]pyrido[2,1-b]quinazolin-10-yl)oxy]methyl]phenyl]-N-hydroxy-, (2E)- | [Molecular Formula]
C29H25FN4O4 | [MOL File]
2411379-14-9.mol | [Molecular Weight]
512.53 |
| Hazard Information | Back Directory | [Uses]
HDAC/Top-IN-1 is an orally active and pan HDAC/Top dual inhibitor with IC50s of 0.036 μM, 0.14 μM, 0.059 μM, 0.089 μM and 9.8 μM for HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8. HDAC/Top-IN-1 efficiently induces apoptosis with S cell-cycle arrest in HEL cells. HDAC/Top-IN-1 has exhibits excellent in vivo antitumor efficacy[1]. | [in vivo]
HDAC/Top-IN-1 exhibits good metabolic properties with a half-life (T1/2) of 31.49 min, and the clearance is 173.32 mL/min/mg[1].
HDAC/Top-IN-1 (5 and 10 mg/kg; PO; daily, for 14 days) exhibits potent oral antitumor activity[1]. | Animal Model: | Female BALB/C nude mice (5-6 weeks, 18-20 g; injected with human K562 cells)[1] | | Dosage: | 5 and 10 mg/kg | | Administration: | PO; daily, for 14 days | | Result: | Exhibited potent oral antitumor activity at 5 mg/kg with a TGI value of 41.4% and a T/C value of 54.3%, and achieved better tumor growth inhibition with a TGI of 68.5% and a T/C of 25.5%. |
| [IC 50]
HDAC1: 34 nM (IC50); HDAC2: 140 nM (IC50); HDAC3: 59 nM (IC50); HDAC6: 89 nM (IC50); HDAC8: 9.8 μM (IC50) | [References]
[1] Wu S, Huang Y, Wang T, et al. Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy. J Med Chem. 2022;65(6):4818-4831. DOI:10.1021/acs.jmedchem.1c02026 |
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