| CAS |
No.383432-38-0 |
| 英文名称 |
CP724714 |
| 分子式 |
C27H27N5O3 |
| 分子量 |
469.54 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Light yellow to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| MDL |
MFCD11983048 |
| SMILES |
CC1=NC=C(C=C1)OC2=C(C=C(C=C2)NC3=NC=NC4=C3C=C(C=C4)C=CCNC(=O)COC)C |
| InChIKey |
LLVZBTWPGQVVLW-SNAWJCMRSA-N |
| InChI |
InChI=1S/C27H27N5O3/c1-18-13-21(8-11-25(18)35-22-9-6-19(2)29-15-22)32-27-23-14-20(7-10-24(23)30-17-31-27)5-4-12-28-26(33)16-34-3/h4-11，13-15，17H，12，16H2，1-3H3，(H，28，33)(H，30，31，32)/b5-4+ |
| PubChem CID |
9874913 |
| 靶点 |
HER2;ErbB2 |
| 通路 |
Angiogenesis; Protein Tyrosine Kinase/RTK |
| 背景说明 |
CP-724714 是HER2/ErbB2抑制剂。 |
| 生物活性 |
CP-724714 is a potent， selective and orally active ErbB2 (HER2) tyrosine kinase inhibitor， with an IC50 of 10 nM. CP-724714 displays a marked selectivity against EGFR kinase (IC50=6400 nM). CP-724714 potently inhibits ErbB2 receptor autophosphorylation in intact cells. Antitumor activities[1][2]. |
| In Vitro |
CP-724714 is >1，000-fold less potent for insulin receptor， insulin-like growth factor-I receptor， platelet-derived growth factor β， vascular endothelial growth factor 2， Abl， Src， c-Met， JNK-2， JNK-3， ZAP-70， Cdk-2， and Cdk-5[1].CP-724714 potently reduces the EGF-induced autophosphorylation of the chimera containing the erbB2 kinase domain at a concentration as low as 50 nmol/L (IC50=32 nM) but is markedly less potent against EGFR[1].CP-724714 (1 μM; 24 hours) induces G1 cell cycle block in vitro in erbB2-overexpressing BT-474 human breast carcinoma cells[1].Cell Cycle Analysis[1]：Cell Line:erbB2-amplified BT-474 breast cancer cells；Concentration:1 μM；Incubation Time: 24 hours；Result:Resulted in accumulation of cells in G1 phase and a marked reduction in S-phase cells. |
| In Vivo |
CP-724714 (3.25-100 mg/kg; p.o.; 0.5-8 hours) results in a concentration-dependent reduction of ErbB2 receptor phosphorylation[1].CP-724714 (6.25-100 mg/kg; p.o.; q.d; for 8 to 40 day) inhibits FRE-erbB2 xenograft growth[1].CP-724714 (Athymic， female FRE-erbB2 xenograft-bearing mice; 30 or 100 mg/kg; p.o.) treatments results in a time- and dose- dependent induction of apoptosis， which was evident as early as 4 to 8 h after dosing. Approximately 75% more tumor cells exhibited apoptotic changes in the 100 mg/kg treatment group compared with vehicle control group at 8 h after dosing. CP-724714 induces regression of BT-474 tumors and significant inhibition in a number of other human tumor xenografts. Additionally， CP-724714 showed a favorable nonclinical toxicity profile with no apparent effects on cardiac tissue[1].Animal Model:Female athymic mice (bearing FRE-erbB2 xenografts)[1]；Dosage: 3.25-100 mg/kg；Administration:P.o.; 0.5-8 hours；Result:Produced a reduction of erbB2 tyrosine phosphorylation in FRE-erbB2 xenografts.Animal Model:Athymic female mice bearing FRE-erbB2 xenografts[1]；Dosage: 6.25- 100 mg/kg；Administration:P.o.; q.d; for 8 to 40 day；Result:Resulted in an inhibition of FRE-erbB2 xenografts. |
| 数据来源文献 |
[1]. Jani JP， et al. Discovery and pharmacologic characterization of CP-724，714， a selective ErbB2 tyrosine kinase inhibitor. Cancer Res， 2007， 67(20)， 9887-9893.
[2]. Feng B， et al. Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724，714. Toxicol Sci， 2009， 108(2)， 492-500. |
| 规格 |
1mg 5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
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