化合物 CA224 T61266

Product Introduction
Bioactivity


英文名: CA224

描述: 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。

体外活性: 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 IC 50 values 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: IC 50 concentration (IC 70 for 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: IC 50 concentration; 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: IC 50 and IC 70 concentration Incubation Time: 24, 48 and 72 h Result: Induces apoptotic cell death in a dose- and time-dependent manner.

体内活性: 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]. Parameter IV (1 mg/kg) Oral (10 mg/kg) t 1/2,β (h) 0.33 1.16 AUC 0-t (ng·h/mL) 187 172 AUC 0-∞ (ng·h/mL) 189 182 C max (ng/mL) 371 190 V d (L/Kg) 2.52 nd V dss (L/Kg) 1.76 nd CL (mL/min/kg) 88.3 nd Bioavailability - 9.6% Time points considered for t 1/2,β calculation 0.5-2 h 1-4 h

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途