CDK4/6-IN-10

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CDK4/6-IN-10 

CDK4/6-IN-10 是一种有效的、选择性的和具有口服活性的 CDK4 和 CDK6 抑制剂，其 IC50 值分别为 22 nM 和 10 nM。CDK4/6-IN-10 显示出抗肿瘤活性。CDK4/6-IN-10 具有研究多发性骨髓瘤 (MM) 的潜力。

CDK4/6-IN-10

CDK4/6-IN-10 Chemical Structure

CAS No. : 2688098-11-3

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生物活性

CDK4/6-IN-10 is a potent, selective and orally active CDK4 and CDK6 inhibitor with IC50s of 22 nM and 10 nM, respectively. CDK4/6-IN-10 shows antitumor activity. CDK4/6-IN-10 has the potential for the research of Multiple myeloma (MM)[1].

IC50 & Target[1]

CDK4

22 nM (IC50)

CDK6/cyclinD1

10 nM (IC50)

体外研究
(In Vitro)

CDK4/6-IN-10 (compouns 32) (1 µM) shows kinase selectivity with IC50s of 22 nM and 10 nM for CDK4 and CDK6, respectively[1].
CDK4/6-IN-10 (72 h) shows antiproliferative activity (GI50s of 2.028, 5.802, 2.286, 2.238, 1.526, 11.381 µM for RPMI-8226, U266, K562, HL-60, 22RV1, HEK-293 cells, respectively)[1].
CDK4/6-IN-10 (0, 1.5, 3, 6 µM, 24 h) induces cell cycle arrest at the G1 phase in a concentration-dependent manner[1].
CDK4/6-IN-10 ( 0, 1, 2, 3 µM, 24 h) induces apoptosis of RPMI-8226 cells in a concentration-dependent manner[1].
CDK4/6-IN-10 (0, 1.5, 3, 6 µM, 24 h) reduces the CDK4/6 activity by decreases the expression level of p-RB, c-MYC and BCL-2[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[1]

Cell Line: RPMI-8226, U266, K562, HL-60, 22RV1, HEK-293 cells
Concentration:
Incubation Time: 72 h
Result: Shows antiproliferative activity (GI50s of 2.028, 5.802, 2.286, 2.238, 1.526, 11.381 µM for RPMI-8226, U266, K562, HL-60, 22RV1, HEK-293 cells, respectively).

Cell Cycle Analysis[1]

Cell Line: RPMI-8226 cells
Concentration: 0, 1.5, 3, 6 µM
Incubation Time: 24 h
Result: Cells were arrested at the G1 phase in a concentration-dependent manner.

Apoptosis Analysis[1]

Cell Line: RPMI-8226 cells
Concentration: 0, 1.5, 3, 6 µM
Incubation Time: 24 h
Result: Reduced the CD4/K activity by decreased the expression level of p-RB, c-MYC and BCL-2.

体内研究
(In Vivo)

CDK4/6-IN-10 (1000, 5000, 10000 mg/kg; p.o.) shows safety profile with LD50 much higher than 10,000 mg/kg[1].
CDK4/6-IN-10 (10 mg/kg; p.o.) shows oral bioavailability (F=51%) in SD rats[1].
CDK4/6-IN-10 (100, 200 mg/kg; p.o., once a day for 19 days) shows antitumor potency and favorable safety profile[1].
Pharmacokinetic Parameters of CDK4/6-IN-10 in SpragueeDawley rats[1].

Compd Admin. Cmax (ng/mL) AUC0-t (h·ng/mL) MRT0-t (h) Tmax (h) t1/2 (h) CL (mL/h/kg) F (%)
32 i.v. 355 960 5.9 0.033 8.9 641 –
p.o. 257 4,878 12.8 10.7 >24 524 51

SpragueeDawley rats, 10 mg/kg, p.o.

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: ICR mice[1]
Dosage: 1000, 5000, 10000 mg/kg
Administration: p.o.
Result: Showed safety profile with LD50 much higher than 10,000 mg/kg.
Animal Model: SpragueeDawley rats[1]
Dosage: 10 mg/kg
Administration: p.o.
Result: Showed oral bioavailability (F=51%).
Animal Model: BALB/c nude mice (6-8 weeks) (MM xenograft model)[1]
Dosage: 100, 200 mg/kg
Administration: p.o., once a day, 19 days
Result: Showed antitumor potency and favorable safety profile.

分子量

418.47

Formula

C22H23FN8
CAS 号

2688098-11-3
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.
参考文献

  • [1]. Yuan K, et al. Discovery of novel and orally bioavailable CDK 4/6 inhibitors with high kinome selectivity, low toxicity and long-acting stability for the treatment of multiple myeloma. Eur J Med Chem. 2022; 228:114024.

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