Defactinib hydrochloride

A FAK inhibitor

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库存: 现货

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包装

价格

促销价

数量
5mg

￥675.00

540.00

- +
10mg

￥1025.00

820.00

- +
50mg

￥2537.00

2030.00

- +
100mg

￥3562.00

2850.00

- +

已选 0 种 0 瓶

金额: ￥0.00

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货号: ajce55896
CAS: 1073160-26-5
别名: VS-6063 hydrochloride; PF 04554878 hydrochloride
分子式: C20H22ClF3N8O3S
分子量: 546.95
纯度: >98%
溶解度: DMSO: 30 mg/mL (54.85 mM); Water: < 0.1 mg/mL (insoluble)
储存: Store at -20°C
库存: 现货

Background

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a vital role in many oncogenic pathways.^1,2 Defactinib is a dose-dependent inhibitor of FAK, with maximal inhibition of FAK autophosphorylation in cells achieved at 10 ?M.³ It is less effective against the related kinase PYK2. Defactinib restores the chemosensitivity of taxane-resistant cells to paclitaxel , although it is not cytotoxic alone.³ Defactinib decreases YB-1 phosphorylation and nuclear accumulation in an Akt-dependent manner. It is orally bioavailable, inhibiting FAK and augmenting paclitaxel action in suppressing the growth and number of ovarian cancer cell tumors in mice.³

1.Schwock, J., Dhani, N., and Hedley, D.W.Targeting focal adhesion kinase signaling in tumor growth and metastasisExpert Opin. Ther. Targets14(1)77-94(2010) 2.Lee, B.Y., Timpson, P., Horvath, L.G., et al.FAK signaling in human cancer as a target for therapeuticsPharmacol. Ther.146132-149(2015) 3.Kang, Y., Hu, W., Ivan, C., et al.Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancerJNCI105(19)1485-1495(2013)

Protocol

Animal experiment:

Mice[1] To determine the antitumor effects of Defactinib, SKOV3ip1, SKOV3-TR, HeyA8, and HeyA8-MDR cells are injected intraperitoneally. One week after tumor cell injection, mice are randomly assigned to 4 groups of 10 mice (control, PTX alone, Defactinib alone, and PTX with Defactinib); treatment is initiated at 3-4 weeks following injection. PTX at 2 mg/kg (SKOV3ip1 and SKOV3-TR) or 2.5 mg/kg (HeyA8 and HeyA8-MDR) is given intraperitoneally weekly; Defactinib at 25 mg/kg is given orally twice every day. Control mice received HBSS intraperitoneally once a week and vehicle orally twice every day. Mice are monitored daily for adverse effects of therapy and are killed on day 35 (SKOV3ip1 or SKOV3-TR), day 28 (HeyA8 or HeyA8-MDR), or when any of the mice seemed moribund. Total body weight, tumor incidence and mass, and the number of tumor nodules are recorded. Tumors are either fixed in formalin or embedded in paraffin or snap frozen in optimal cutting temperature (OCT) compound in liquid nitrogen.

参考文献:

[1]. Kang Y, et al. Role of focal adhesion kinase in regulating YB-1-mediated resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95.