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ARRY-520 R enantiomer
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。
ARRY-520 R enantiomer图片
CAS NO:885060-08-2
规格:98%
分子量:420.48
包装与价格:
包装价格(元)
5mg电议
10mg电议
50mg电议
200mg电议

产品介绍
KSP inhibitor
CAS:885060-08-2
分子式:C20H22F2N4O2S
分子量:420.48
纯度:98%
存储:Store at -20°C

Background:

Kinesin spindle protein (KSP) is one member of the mitotic kinesins involved in the early stages of mitosis responsible for centrosome separation. As the R form of ARRY-520, ARRY-520 R enantiomer is a synthetic, small molecule KSP inhibitor.
In vitro: ARRY-520 had low nanomolar antiproliferative activity in various tumor cell lines and exhibited activity in multidrug-resistant cell lines. EC50s of ARRY-520 for proliferation inhibition in HCT-15, NCI/ADR-RES and K562/ADR cells was 3.7, 14 and 4.2 nM, respectively, while paclitaxel EC50s in these cell lines was 35, 565 and 372 nM. Moreover, K562/ADR was found to be 118-fold resistant to paclitaxel when compared to the parent K562 line, but only 3.5-fold resistant to that of ARRY-520 [1].
In vivo: ARRY-520 was found to be active in UISO-BCA-1 xenografts, which were completely resistant to paclitaxel. The antitumor efficacy of ARRY-520 was also found to be superior to paclitaxel in mice bearing HT-29, HCT-116, MDA-MB-231 and A2780 xenografts. ARRY-520 was superior to docetaxel in the androgen receptor-negative prostate cancer PC-3 xenograft model, and was also superior to docetaxel in the DU145 prostate xenograft model [1].
Clinical trial: A phase I trial was conducted to establish the safety and the maximum tolerated dose (MTD) of ARRY-520. The MTD was 4.5 mg/m2 total dose per cycle for both dose schedules. Dose-limiting toxicities included exfoliative rash, hand-foot-syndrome, mucositis, and hyperbilirubinemia. Grades 3 or 4 reversible drug-related myelosuppression were observed in 33 of 36 patients [2].
Reference:
[1] Woessner R, Tunquist B, Lemieux C, Chlipala E, Jackinsky S, Dewolf W Jr, Voegtli W, Cox A, Rana S, Lee P, Walker D. ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane-resistant tumor models. Anticancer Res. 2009;29(11):4373-80.
[2] Khoury HJ, Garcia-Manero G, Borthakur G, Kadia T, Foudray MC, Arellano M, Langston A, Bethelmie-Bryan B, Rush S, Litwiler K, Karan S, Simmons H, Marcus AI, Ptaszynski M, Kantarjian H. A phase 1 dose-escalation study of ARRY-520, a kinesin spindle protein inhibitor, in patients with advanced myeloid leukemias. Cancer. 2012;118(14):3556-64.