CAS號	2200214-93-1	產(chǎn)地	國產(chǎn)
規(guī)格	5mg	級別	化工級
證書	ISO系列證書

SHP099 單鹽酸鹽

SHP099 hydrochloride是有效，選擇性，有口服活性的 SHP2 抑制劑，IC₅₀值為70 nM。

生物活性

SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC₅₀ of 70 nM^[1].

IC₅₀ & Target

IC50: 70 nM (SHP2)^[1]

體外研究(In Vitro)

The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC₅₀ of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells^[1]. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells^[2].

體內(nèi)研究(In Vivo)

After a single doses of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg^[1].

分子量：388.72

性狀：Solid

Formula：C₁₆H₂₀Cl₃N₅

CAS 號：2200214-93-1

運輸條件

Room temperature in continental US; may vary elsewhere.

儲存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性數(shù)據(jù)

In Vitro:

DMSO : 4.1 mg/mL (10.55 mM; Need ultrasonic and warming)

H₂O : ≥ 2.5 mg/mL (6.43 mM)

* "≥" means soluble, but saturation unknown.

配制儲備液

1 mM	2.5725 mL	12.8627 mL	25.7255 mL
5 mM	0.5145 mL	2.5725 mL	5.1451 mL
10 mM	0.2573 mL	1.2863 mL	2.5725 mL

請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。
儲備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 儲存時，請在 6 個月內(nèi)使用，-20°C 儲存時，請在 1 個月內(nèi)使用。

In Vivo:

請根據(jù)您的實驗動物和給藥方式選擇適當?shù)娜芙夥桨?。以下溶解方案都請先按?In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：

——為保證實驗結果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當天使用；以下溶劑前顯示的百
分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

1.

請依序添加每種溶劑： 50% PEG300 50% saline
Solubility: 20 mg/mL (51.45 mM); Suspended solution; Need ultrasonic
2.

請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (6.43 mM); Clear solution

參考文獻

[1]. Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. [Content Brief]

[2]. Chen YN, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52. [Content Brief]
[3]. Carmine Fedele, et al. SHP2 Inhibition Abrogates MEK inhibitor Resistance in Multiple Cancer Models. bioRxiv. April 25, 2018.

注：產(chǎn)品僅用于科研