Pimitespib - CAS:1260533-36-5

您当前的位置：

Pimitespib (Synonyms:TAS-116)

目录号 : KM9110 CAS No. : 1260533-36-5 纯度 : 98%

Data Sheet 产品使用指南

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。

规格	价格	是否有货
5mg		In-stock
10mg		In-stock
50mg		In-stock
100mg		In-stock
200mg	询价	In-stock
500mg	询价	In-stock

查看所有商品（1）

加入购物车大包装询价

Other Forms of Rapamycin:

Ginkgolide B In-stock
Isoginkgetin In-stock
Ginkgolic acid C17:1 In-stock
Ginkgolic Acid In-stock
Propargyl-PEG4-amine In-stock

KKL Med 的所有产品和服务仅用于科学研究，不能被用于人体，兽医，我们也不向个人提供产品和服务。

生物活性

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

体外研究

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.

Cell Viability Assay

Cell Line:	Human retinal pigment epithelial ARPE-19 cell lines and NCI-H929 MM cells
Concentration:	0-5 μM
Incubation Time:	48 hours
Result:	Inhibited NCI-H929 MM cells growth with an IC₅₀ of 0.35 μM.

Western Blot Analysis

Cell Line:	MM cell lines INA6 and NCI-H929 cells
Concentration:	0.125-1 μM
Incubation Time:	24 hours
Result:	Targeted potently HSP90 client proteins including C-Raf and MEK1/2; as well as inhibited upregulation of HSP27 and overcomes 17-AAG resistance mechanisms.

体内研究

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 Pimitespib-treated mice vs. vehicle-treated mice) is 47%, 21%, and 9% for doses of 3.6 mg/kg, 7.1 mg/kg, and 14.0 mg/kg, respectively. Pimitespib is orally absorbed and has a bioavailability of almost 100% in mice, and 69.0% in rats. Pimitespib has moderate terminal elimination half-life (t_1/2=8.2 h, 2.5 h, 4.4 h and 2.2 h for mouse (3.6 mg/kg, p.o.), mouse (7.1 mg/kg, p.o.), mouse (14.0 mg/kg, p.o.), rat (4 mg/kg, p.o.)). Pimitespib is more rapidly eliminated from retina (t_1/2=3.4 hours) than the other HSP90 inhibitors (t_1/2=7.1-19.1 hours).

Animal Model:	Male F344 nude rats (6 weeks old) with established NCI-H1975 xenografts (6 weeks old)
Dosage:	12.0 mg/kg
Administration:	Oral administration; daily; two weeks
Result:	Led to tumor shrinkage. Showed antitumor activity without inducing eye injury in rats and did not cause ocular toxicity at the effective dose in the NCI-H1975 rat xenograft model.

Animal Model:	CB17 SCID mice (48-54 days old) with murine xenograft model
Dosage:	10 and 15 mg/kg
Administration:	Oral administration; 5 days a week; for 28 days
Result:	Enhanced significantly growth inhibition versus the vehicle control group. The delay in tumor growth was greater in the combination-treated group compared with either monotherapy cohort.

Animal Model:	Mice, Rats, and Dogs
Dosage:	3.0 mg/kg for dogs, 4.0 mg/kg for rats, 3.6, 7.1 and 14.0 mg/kg for mice
Administration:	Oral administration; daily; 20 days
Result:	Absorbed orally and had a bioavailability of almost 100% in mice, 69.0% in rats, and 73.9% in dogs without special formulation.

分子式

C₂₅H₂₆N₈O

分子量

454.53

CAS号

1260533-36-5

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性数据

In Vitro:

DMSO : 125 mg/mL (275.01 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.2001 mL	11.0004 mL	22.0007 mL
5 mM	0.4400 mL	2.2001 mL	4.4001 mL
10 mM	0.2200 mL	1.1000 mL	2.2001 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.08 mg/mL (4.58 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.58 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.08 mg/mL (4.58 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.58 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.58 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.58 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

临床试验

纯度： 98%

Data Sheet

产品使用指南

摩尔计算器
稀释计算器

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量

浓度

体积

分子量*

重置计算

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2

浓度

体积

浓度

体积

重置计算

Other Forms of Rapamycin:

KKL 顾客使用本产品发表的 0 篇科研文献

The molarity calculator equation

The dilution calculator equation