XL888

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

XL888 是 Hsp90 的 ATP 竞争性抑制剂 (IC50: 24 nM)。热休克蛋白 90 (Hsp90) 是一种伴侣蛋白，可维持参与细胞增殖、细胞周期和细胞凋亡的客户蛋白的功能。

XL888 is an orally bioavailable, ATP-competitive, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor XL888 specifically binds to Hsp90, inhibiting its chaperone function and promoting the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival; inhibition of tumor cell proliferation may result. Hsp90, a chaperone complex protein upregulated in a variety of tumor cell types, regulates the folding and degradation of many oncogenic signaling proteins, including Her-2 and Met.(In Vitro):XL888 is a heat shock protein-90 (HSP90) inhibitor. Treatment with XL888 leads to dose dependent decreases in the growth of all the cell lines with no significant difference in IC50 values observed between the naive and resistance pairs of cell lines (t=0.25, p=0.82). Treatment of all of the vemurafenib resistant cell lines with XL888 (300 nM) induces high levels (>66%) of apoptosis, caspase-3 cleavage and loss of mitochondrial membrane potential (TMRM) in every cell line tested. Treatment of cell lines that are na?ve, intrinsically resistant and with acquired vemurafenib resistance with XL888 (300 nM) leads to robust time-dependent increases in the expression of HSP70 isoform 1 (HSP71).(In Vivo):Treatment of the established M245 tumors with XL888 (125 mg/kg 3× week) leads to a significant slowing of tumor growth (P=0.017) without any effect upon animal weights. Analysis of xenograft specimens by LC-MRM shows a marked increase in intratumoral HSP70 expression following XL888 treatment. It is noted that the XL888 is well tolerated by the mice, with no significant alterations in body weigh observed over the study period. LC-MRM mediated analysis of xenograft samples following 15-days of XL888 treatment shows a robust (8.6-fold) increase in intratumoral HSP70 expression compare to controls.

XL888 is a heat shock protein-90 (HSP90) inhibitor. Treatment with XL888 leads to dose dependent decreases in the growth of all the cell lines with no significant difference in IC50 values observed between the naive and resistance pairs of cell lines (t=0.25, p=0.82). Treatment of all of the vemurafenib resistant cell lines with XL888 (300 nM) induces high levels (>66%) of apoptosis, caspase-3 cleavage and loss of mitochondrial membrane potential (TMRM) in every cell line tested. Treatment of cell lines that are na?ve, intrinsically resistant and with acquired vemurafenib resistance with XL888 (300 nM) leads to robust time-dependent increases in the expression of HSP70 isoform 1 (HSP71).

Treatment of the established M245 tumors with XL888 (125 mg/kg 3× week) leads to a significant slowing of tumor growth (P=0.017) without any effect upon animal weights. Analysis of xenograft specimens by LC-MRM shows a marked increase in intratumoral HSP70 expression following XL888 treatment.It is noted that the XL888 is well tolerated by the mice, with no significant alterations in body weigh observed over the study period. LC-MRM mediated analysis of xenograft samples following 15-days of XL888 treatment shows a robust (8.6-fold) increase in intratumoral HSP70 expression compare to controls.

XL888 | XL-888 | XL 888

Endocrinology/Hormones

5-HT Receptor

HSP90

Cancer

——

1149705-71-4

503.6

C29H37N5O3

>98% (HPLC)

DMSO : ≥ 100 mg/mL; 198.55 mM

CC[C@@H](C)Nc1c(cc(C)c(c1)C(=O)NC1CC2CCC(C1)N2c1ncc(cc1)C(=O)C1CC1)C(=O)N

5-((R)-sec-butylamino)-N1-((1R,3s,5S)-8-(5-(cyclopropanecarbonyl)pyridin-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-2-methylterephthalamide

(-20℃)

With Ice Pack

≥ 2 years