[1]. Liu WS, et al. Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation. J Comput Aided Mol Des. 2019 Aug;33(8):759-774.
[2]. 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.
SHP394 is an orally active, selective and allosteric inhibitor of SHP2, with an IC50 of 23 nM[1].
IC50 & Target
IC50: 23 nM (SHP2)[1]
体外研究 (In Vitro)
SHP394 inhibits Caco-2 cells proliferation with the IC50 of 297 nM[1]. SHP394 exhibits antiproliferation activity against the Detroit-562 pharyngeal carcinoma cell line in vitro (IC50= 1.38 μM) [1]. SHP394 decreases p-ERK with an IC50 of 18 nM KYSE520 cells[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
[1]. Sarver P, et al. 6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors. J Med Chem. 2019 Feb 28;62(4):1793-1802.
Remetinostat (SHP-141) 是一种基于羟肟酸的组蛋白去乙酰化酶 (HDAC) 的抑制剂,目前正在开发应用于研究皮肤 T 细胞淋巴瘤。
Remetinostat Chemical Structure
CAS No. : 946150-57-8
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生物活性
Remetinostat (SHP-141) is a hydroxamic acid-based inhibitor of histone deacetylase enzymes (HDAC) which is under development for the treatment of cutaneous T-cell lymphoma[1].
IC50 & Target
HDAC[1].
Clinical Trial
分子量
323.34
Formula
C16H21NO6
CAS 号
946150-57-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Yijun Deng, et al. Process Development of the Soft Histone Deacetylate Enzyme Inhibitor SHP-141: Acylation of Methyl Paraben and Suberyl Hydroxamic Acid Formation. Org. Process Res. Dev. 2016, 20, 10, 1812-1820.
PHPS1 sodium is a potent and selective Shp2 inhibitor with Kis of 0.73, 5.8, 10.7, 5.8, and 0.47 μM for Shp2, Shp2-R362K, Shp1, PTP1B, and PTP1B-Q, respectively[1].
PHPS1 (30 μM; 6 days) inhibits proliferation of human tumor cells[1]. PHPS1 (5-20 μM; 5-360 minutes) inhibits Erk1/2 but not Akt and Stat3 phosphorylation in a dose-dependent manner[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
Human cancer cell lines MDA-MB-435, HCT-116 (colon carcinoma), HCT-15 (colon carcinoma), PC-3 (prostate carcinoma), HT-29 (colon carcinoma), NCI-H661 (lung carcinoma), and Caki-1 (kidney carcinoma)
Concentration:
30 μM
Incubation Time:
6 days
Result:
Resulted in a reduction in cell number of between 0% (Caki-1) to 74% (HT-29).
Western Blot Analysis[1]
Cell Line:
Madin-Darby canine kidney (MDCK) cells
Concentration:
5, 10, 20 μM
Incubation Time:
5, 15, 60, 120, 360 minutes
Result:
Inhibited HGF/SF (1 unit/mL)-induced phosphorylation and thus activation of Erk1/2 over a time period of 15 min to 6 h. In contrast, transient phosphorylation of Erk1/2 after 5 min was not affected. Exhibited no effect on HGF/SF-induced activation of PI3K/Akt or Stat3.
体内研究 (In Vivo)
PHPS1 (3 mg/kg; i.p. injection; every day during the last week on the high-fat diet) renders Ldlr-/- mice less susceptible to atherosclerosis development[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Ldlr-/- (005061) mice[2]
Dosage:
3 mg/kg
Administration:
Intraperitoneal (i.p.) injection; every day during the last week on the high-fat diet.
Result:
Revealed a significant decrease in atherosclerotic plaque size in the aorta compared with the other two groups.
分子量
487.42
Formula
C21H14N5NaO6S
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Klaus Hellmuth, et al. Specific Inhibitors of the Protein Tyrosine Phosphatase Shp2 Identified by High-Throughput Docking. Proc Natl Acad Sci U S A. 2008 May 20;105(20):7275-80.
[2]. Jia Chen, et al. SHP2 Inhibitor PHPS1 Protects Against Atherosclerosis by Inhibiting Smooth Muscle Cell Proliferation. BMC Cardiovasc Disord. 2018 Apr 27;18(1):72.