KPT276

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

KPT-276 是一种口服生物可利用的选择性核输出抑制剂 (SINE)，它不可逆地与 CRM1 结合并阻断 CRM1 的功能。

KPT-276 analog of KPT-185 is an orally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of CRM1. IC50 value: Target: CRM1 in vitro: A selective inhibitor of nuclear export compound KPT-276 specifically and irreversibly inhibits the nuclear export function of XPO1. The viability of 12 HMCLs treated with KTP-276 was significantly reduced. KPT-276 also actively induced apoptosis in primary MM patient samples. In gene expression analyses two genes of probable relevance were dysregulated by KPT-276: cell division cycle 25 homolog A (CDC25A) and bromodomain-containing protein 4 (BRD4) both of which are associated with c-MYC pathway. Inhibition of CRM1 by two novel selective inhibitors of nuclear export (SINE) KPT-185 and KPT-276 in MCL cells resulted in significant growth inhibition and apoptosis induction. KPT-185 also induced CRM1 accumulation in the nucleus resulting in CRM1 degradation by the proteasome. in vivo: One week after leukemic cell inoculation the mice were given KPT-276 at 150 mg/kg via oral gavage 3 times a week or vehicle control. KPT-276 has the identical CRM1 binding warhead and specificity as KPT-185 similar biologic activity in vitro but superior oral bioavailability and pharmacokinetics which allow it to be used in vivo. Mice were monitored for survival. Some mice were killed at day 21 to assess the effects of KPT-276 on leukemia burden by measuring spleen weight and white blood cell count. Oral administration of KPT-276 significantly suppressed tumor growth in an MCL-bearing severe combined immunodeficient mouse model without severe toxicity.

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KPT 276 | KPT-276

Membrane Transporter/Ion Channel

CRM1

CRM1

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1421919-75-6

426.26

C16H10F8N4O

>98% (HPLC)

DMSO:16 mg/mL (37.5 mM); Ethanol:<1 mg/mL;Water:<1 mg/mL

C1C(CN1C(=O)/C=C\n1cnc(n1)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)(F)F

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(-20℃)

With Ice Pack

≥ 2 years