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CA224
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
CA224图片
CAS NO:883561-04-4
包装与价格:
包装价格(元)
100mg电议
250mg电议
500mg电议

产品介绍
CA224 (Compound 1) 是一种选择性的、具有口服活性的Cdk4–cyclin D1抑制剂,IC50值为 6.2 μM。CA224 诱导细胞凋亡 (apoptosis),具有抗肿瘤活性。
生物活性

CA224 (Compound 1) is a selective and orally activeCdk4–cyclin D1inhibitor with anIC50of 6.2 μM. CA224 induces cellapoptosisand shows antitumor activity[1].

IC50& Target

cdk4-cyclin D1

6.2 μM (IC50)

cdk2-cyclin A

521 μM (IC50)

体外研究
(In Vitro)

CA224 (Compound 1) (48 h) shows antiproliferation activity against human cancer cell lines[1].
CA224 (18-48 h) blocks the growth of cancer cells at G0/G1 and G2/M phase of the cell cycle, and selectively kills SV40 large T-antigen transformed normal mouse embryonic liver cells (BNL SV A.8)[1][2].
CA224 (0-4 μM, 30 min) inhibits tubulin polymerization and enhances the depolymerization of stabilized tubulin protein[1].
CA224 (0-72 h) induces cell apoptosis in cancer cells[1].
CA224 (10 μM) shows 50%, 14%, 51% and 19% inhibition of CYP3A4, CYP2D6, CYP2C9, and CYP2C19, respectively[1].

Cell Proliferation Assay[1]

Cell Line:LS174T, PC-3, MiaPaCa, A549, Calu-1, NCI-H460, NCI-H1299, NCI-H358, BNL CL2 and BNL SV A.8
Concentration:
Incubation Time:48 h
Result:Showed antiproliferation activity with IC50values of 3.5, 6.2, 4.0, 3.5, 11.5, 2.0, 2.5, 2.2, 2.6 and 3.8 uM against LS174T, PC-3, MiaPaCa, A549, Calu-1, NCI-H460, NCI-H1299, NCI-H358, BNL CL2 and BNL SV A.8, respectively.

Cell Cycle Analysis[1][2]

Cell Line:A549, NCI-H1299, NCI-H358, BNL CL2, BNL SV A.8 and Calu-1
Concentration:IC50concentration (IC70for Calu-1)
Incubation Time:24 h for A549, NCI-H1299 and Calu-1, 18 h for NCI-H358, 48 h for BNL CL2 and BNL SV A.8
Result:Induced a profound block at G2/M in A549 and NCI-H1299 cells. Maintained nocodazole- and paclitaxel-induced G2/M block in NCI-H358 cells. Exhibited prominent G2/M arrest in BNL CL2 cells. 31% of cells were detected in sub-G1 phase (control: 0%) in BNL SV A.8 cells. Retained the G0/G1 block in serum-starved p53-null Calu-1 cells.

Western Blot Analysis[1]

Cell Line:A549 and LS174T
Concentration:IC50concentration; 1, 2, 3 and 4 μM for tubulin polymerization
Incubation Time:24 h; 30 min for tubulin polymerization in A549 cells
Result:Induced p53, p21, and p27. Downregulated cyclin B1 and Cdk1. Inhibited tubulin polymerization in a dose-dependent manner and resulted in accumulation of unassembled tubulin in the supernatant.

Apoptosis Analysis[1]

Cell Line:A549, NCI-H460, NCI-H358, and NCI-H1299
Concentration:IC50and IC70concentration
Incubation Time:24, 48 and 72 h
Result:Induces apoptotic cell death in a dose- and time-dependent manner.
体内研究
(In Vivo)

CA224 (Compound 1) (100 mg/kg; i.p.; once a day for 9 days) shows significant tumor growth inhibition without obvious toxicity[1].

Animal Model:The severe combined immunodeficient (SCID) mouse, lacking both T and B immune cells. Male mice weighing 18–25 g, 6–8 weeks of age for subcutaneous injection of HCT-116, female mice weighing 15–24 g, 6–8 weeks of age for subcutaneous injection of NCI-H460[1]
Dosage:100 mg/kg
Administration:Intraperitoneal injection, once a day for 9 consecutive days
Result:Showed significant tumor growth inhibition in both HCT-116 and NCI-H460 tumor models without significant bodyweight loss.
Animal Model:BALB/c mice[1]
Dosage:10 mg/kg (oral administration) or 1.0 mg/kg (intravenous injection)
Administration:Oral or intravenous injection (Pharmacokinetics Analysis)
Result:Pharmacokinetics parameters determined for CA224 after IV and PO administration[1].
ParameterIV (1 mg/kg)Oral (10 mg/kg)
t1/2,β(h)0.331.16
AUC0-t(ng·h/mL)187172
AUC0-∞(ng·h/mL)189182
Cmax (ng/mL)371190
Vd(L/Kg)2.52nd
Vdss(L/Kg)1.76nd
CL (mL/min/kg)88.3nd
Bioavailability-9.6%
Time points considered
for t1/2,βcalculation
0.5-2 h1-4 h
分子量

354.44

Formula

C24H22N2O

CAS 号

883561-04-4

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.