HDAC-IN-50

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HDAC-IN-50

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CAS NO:

2653339-26-3

HDAC-IN-50 是一种有效的，具有口服活性的FGFR和HDAC双重抑制剂，对 FGFR1, FGFR2, FGFR3, FGFR4, HDAC1, HDAC2, HDAC6, HDAC8 的IC₅₀值分别为 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM。HDAC-IN-50 诱导细胞凋亡(Apoptosis) 和细胞周期停滞在 G0/G1 期。HDAC-IN-50 降低 pFGFR1、pERK、pSTAT3 的表达。HDAC-IN-50 具有抗肿瘤活性。

生物活性

HDAC-IN-50 is a potent and orally activeFGFRandHDACdual inhibitor withIC₅₀values of 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM forFGFR1,FGFR2,FGFR3,FGFR4,HDAC1,HDAC2,HDAC6,HDAC8, respectively. HDAC-IN-50 inducesApoptosisand 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].

IC₅₀& Target^[1]

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)

体外研究
(In Vitro)

HDAC-IN-50 (compound 10e) (0.1, 1, 10, 100 nM; 12-84 h) induces apoptosis and cell cycle arrest at G0/G1 phase in a time and dose-dependent manner^[1].
HDAC-IN-50 (0, 1.25, 2.5, 5 μM for HCT116 cells, 0, 1, 10, 100 nM for SNU-16 cells; 36 h) decreases the expression of pFGFR1, pERK, pSTAT3 in a dose-dependent manner^[1].

Cell Proliferation Assay^[1]

Cell Line:	HCT116, SNU-16, KATO III, A2780, K562, Jurkat cells
Concentration:	0-30 μM
Incubation Time:	72 h
Result:	Showed antiproliferative activities with IC₅₀s of 0.82, 0.0007, 0.0008, 0.04, 2.46, 15.14 μM for HCT116, SNU-16, KATO III, A2780, K562, Jurkat cells, respectively.

Cell Cycle Analysis^[1]

Cell Line:	SNU-16 cells
Concentration:	0.1, 1, 10, 100 nM
Incubation Time:	12, 24, 36 h
Result:	Induced cell cycle arrest at G0/G1 phase in a time and dose-dependent manner.

Apoptosis Analysis^[1]

Cell Line:	SNU-16 cells
Concentration:	0.1, 1, 10, 100 nM
Incubation Time:	36, 48, 60, 72, 84 h
Result:	Induced apoptosis with the apoptotic rate increased 30.8% and 49.6% at 10, 100 nM, respectively.

Western Blot Analysis^[1]

Cell Line:	HCT116, SNU-16 cells
Concentration:	0, 1.25, 2.5, 5 μM for HCT116 cells, 0, 1, 10, 100 nM for SNU-16 cells
Incubation Time:	36 h
Result:	Reduced the expression of pFGFR1, pERK, pSTAT3 in a dose-dependent manner.

体内研究
(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	T_1/2(h)	T_max(h)	C_max(ng/mL)	AUC_0-∞(h·ng/mL)	CL (mL/min/kg)	V_ss(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.

分子量

575.70

Formula

C₃₁H₄₁N₇O₄

CAS 号

2653339-26-3

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.