1333151-73-7

Basic information

• Product Name: KPT-185
• Synonyms: KPT-185;(2Z)-3-[3-[3-Methoxy-5-(trifluoromethyl)phenyl]-1H-1,2,4-triazol-1-yl]-2-propenoic acid 1-methylethyl ester;2-Propenoic acid, 3-[3-[3-methoxy-5-(trifluoromethyl)phenyl]-1H-1,2,4-triazol-1-yl]-, 1-methylethyl ester, (2Z)-;(2Z)-3-[3-[3-Methoxy-5-(trifluoromethyl)phenyl]-1H-1,2,4-triazol-1-yl]-2-propenoic acid 1-methylethyl ester KPT185;KPT-185, >=98%;(Z)-Isopropyl 3-(3-(3-methoxy-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate
• CAS NO: 1333151-73-7
• Molecular Formula: C₁₆H₁₆F₃N₃O₃
• Molecular Weight: 355.3117496
• Product Categories: Inhibitors
• Mol File: 1333151-73-7.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Solubility: insoluble in H2O; ≥17.77 mg/mL in DMSO; ≥25.2 mg/mL in EtOH
• CAS DataBase Reference: KPT-185(CAS DataBase Reference)
• NIST Chemistry Reference: KPT-185(1333151-73-7)
• EPA Substance Registry System: KPT-185(1333151-73-7)

Safety Data

• Hazardous Substances Data: 1333151-73-7(Hazardous Substances Data)

Usage

Uses

KPT185 acts as a novel CRM1 inhibitor used in the treatment of acute myeloid leukemia.

Biological Activity

kpt-185 is a selective and irreversible inhibitor of chromosome maintenance protein 1 (crm1) with ic50 values of 100-500nm [1].crm1 is an important nuclear protein export receptor. blocking crm1-mediated nuclear export can result in the suppression of tumors. as an inhibitor of crm1, kpt-185 binds crm1within the cys528 site and prevents crm1from interacting with tumor-suppressor proteins. in the in vitro studies on aml cell lines, kpt-185 inhibits proliferation of a variety of leukemia cells with ic50 values ranging from 100nm to 500nm. it induces cell-cycle arrest at g1 and induces apoptosis. kpt-185 also strongly affects cell colony formation. in addition, the inhibition of crm1 caused by kpt-185 induces differentiation of aml blast. besides that, kpt-185 is also found to inhibit proliferation and induce apoptosis of pancreatic cancer cells including colo-357, hpac and bxpc-3 [1, 2].

references

[1] ranganathan p, yu x, na c, et al. preclinical activity of a novel crm1 inhibitor in acute myeloid leukemia. blood, 2012, 120(9): 1765-1773.[2] azmi a s, aboukameel a, bao b, et al. selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. gastroenterology, 2013, 144(2): 447-456.

Upstream product

• 96088-62-9 isopropyl propiolate 
• 1333153-10-8 3-(3-methoxy-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazole 
• 868167-61-7 3-methoxy-5-(trifluoromethyl)benzonitrile 
• 1251940-10-9 C₉H₈F₃NOS 
• 1333153-09-5 C₁₀H₁₀F₃NOS 
• 1333154-26-9 (Z)-isopropyl 3-iodoacrylate 

Downstream Products

• 1333154-08-7 (Z)-3-(3-(3-methoxy-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid 
• 1333151-95-3 (Z)-azetidin-3-yl 3-(3-(3-methoxy-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate 
• 1333152-18-3 (Z)-1-(3,3-difluoroazetidin-1-yl)-3-(3-(3-methoxy-5-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)prop-2-en-1-one 

Relevant articles and documents

HYDRAZIDE CONTAINING NUCLEAR TRANSPORT MODULATORS AND USES THEREOF

The invention generally relates to nuclear transport modulators, e.g., CRM1 inhibitors, and more particularly to a compound represented by structural formula (I): or a pharmaceutically acceptable salt thereof, wherein the values and alternative values for the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of structural formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with CRM1 activity.