| Identification | Back Directory | [Name]
1H-Pyrazole-1-heptanamide, 4-[7-[(3,5-dimethoxyphenyl)[2-[(1-methylethyl)amino]ethyl]amino]-2-quinoxalinyl]-N-hydroxy- | [CAS]
2653339-26-3 | [Synonyms]
HDAC-IN-50
1H-Pyrazole-1-heptanamide, 4-[7-[(3,5-dimethoxyphenyl)[2-[(1-methylethyl)amino]ethyl]amino]-2-quinoxalinyl]-N-hydroxy- | [Molecular Formula]
C31H41N7O4 | [MOL File]
2653339-26-3.mol | [Molecular Weight]
575.7 |
| Hazard Information | Back Directory | [Uses]
HDAC-IN-50 is a potent and orally active FGFR and HDAC dual inhibitor with IC50 values of 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM for FGFR1, FGFR2, FGFR3, FGFR4, HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-50 induces Apoptosis and cell cycle arrest at G0/G1 phase. HDAC-IN-50 decreases the expression of pFGFR1, pERK, pSTAT3. HDAC-IN-50 shows anti-tumor activity[1]. | [in vivo]
HDAC-IN-50 (15, 30 mg/kg; p.o.; daily for 18 days) shows anti-tumor activity in mouse[1].
Pharmacokinetic Parameters of HDAC-IN-50 in female Sprague–Dawley (SD) rats[1].
| dose (mg/kg) | administration route | T1/2 (h) | Tmax (h) | Cmax (ng/mL) | AUC0-∞ (h·ng/mL) | CL (mL/min/kg) | Vss (mL/kg) | F % | | 2 | IV | 0.98± 0.12 | 0.08 | 1116.63 ± 320.45 | 424.88 ± 89.56 | 80.64 ± 15.59 | 2788.87 ± 765.11 | | | 5 | IP | 1.83 ± 0.06 | 2 | 101.57 ± 23.05 | 491.25 ± 84.18 | | | 43.83 | | 30 | PO | 0.77 ± 0.04 | 4 | 442.53 ± 46.33 | 1557.12 ± 355.61 | | | 24.83 |
Female Sprague-Dawley (SD) rats, 5 mg/kg iv; 5 mg/kg ip; 30 mg/kg p.o. [1]| Animal Model: | BALB/c nude mice (HCT116 xenograft model)[1] | | Dosage: | 15, 30 mg/kg | | Administration: | P.o.; daily for 18 days | | Result: | Inhibited the tumor growth and downregulated the expression of pSTAT3, pFGFR1, increased the expression of Ac-H3. |
| [IC 50]
FGFR1: 0.18 nM (IC50); FGFR2: 1.2 nM (IC50); FGFR3: 0.46 nM (IC50); FGFR4: 1.4 nM (IC50); HDAC1: 1.3 nM (IC50); HDAC2: 1.6 nM (IC50); HDAC6: 2.6 nM (IC50); HDAC8: 13 nM (IC50) | [References]
[1] Wan G, et al. Design and Synthesis of Fibroblast Growth Factor Receptor (FGFR) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Cancer. J Med Chem. 2022 Dec 22;65(24):16541-16569. DOI:10.1021/acs.jmedchem.2c01413 |
|
|