Pimitespib (TAS-116) 是口服生物可利用的，ATP 竞争性的，高特异性的 HSP90α/HSP90β 抑制剂，K_i 值分别为 34.7 nM 和 21.3 nM。不抑制其他 HSP90 家族蛋白如 GRP94。Pimitespib 具有较低的眼部毒性。

Pimitespib (TAS-116) is an oral bioavailable, ATP-competitive, highly specific HSP90α/HSP90β inhibitor (K i s of 34.7 nM and 21.3 nM, respectively) without inhibiting other HSP90 family proteins such as GRP94. Pimitespib demonstrates less ocular toxicity.

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HSP90α 34.7 nM (Ki) HSP90β 21.3 nM (Ki)

Pimitespib binds not only to the conventional-binding pockets as existing Hsp-90 inhibitors, but also to a novel-binding pocket. Such a unique binding mode makes Pimitespib highly specific for Hsp-90α/β without inhibiting other Hsp-90 family proteins such as GRP94 in endoplasmic reticulum or TRAP-1 in mitochondria.
Pimitespib (0-5 μM, 48 hours) inhibits human retinal pigment epithelial ARPE-19 cell lines and NCI-H929 MM cells growth.
More significant degradation of p-C-Raf and p-MEK1/2, HSP90 client proteins and key RAS/RAF/MEK pathway regulators, is triggered by Pimitespib (0.125-1 μM, 24 hours) than 17-AAG in INA6 and NCI-H929 MM cells.
has not independently confirmed the accuracy of these methods. They are for reference only.

Pimitespib (12.0 mg/kg, p.o., 14 days) shows antitumor activity without inducing eye injury in rats. Pimitespib is distributed less in retina than in plasma in rats; consequently, Pimitespib does not produce any detectable photoreceptor injury. Pimitespib triggers enhanced in vivo anti-MM activities, both alone and in combination with PS-341 (BTZ), with a favorable safety profile. Mice treated with Pimitespib (10 mg/kg and 15 mg/kg, orally, 38 days), BTZ, or Pimitespib plus BTZ show significantly enhance growth inhibition versus the vehicle control group. Median overall survival of treated animals (Pimitespib, orally, 10 mg/kg=33 days, 15 mg/kg=37 days, BTZ=36 days, and the combination=56.5 days) is significantly longer than vehicle control.
The favorable pharmacokinetic profile of Pimitespib is reflected in its dose-dependent antitumor activity; the T/C (tumor volume of

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Powder -20°C 3 years；4°C 2 years

[1]. Ohkubo S, et al. TAS-116, a highly selective inhibitor of heat shock protein 90α and β, demonstrates potent antitumor activity and minimal ocular toxicity in preclinical models. Mol Cancer Ther. 2015 Jan;14(1):14-22.
[2]. Suzuki R, et al. Anti-tumor activities of selective HSP90α/β inhibitor, TAS-116, in combination with PS-341 in multiple myeloma. Leukemia. 2015 Feb;29(2):510-4.

In Vitro: DMSO : 125 mg/mL (275.01 mM; Need ultrasonic)配制储备液