Upamostat

CAS: 590368-25-5

Chemical Formula: C32H47N5O6S

Exact Mass: 629.32470

Synonym:  WX 671; WX-671; WX671. Upamostat; Brand name: Mesupron.

IUPAC/Chemical name: 

(S)-ethyl 4-(3-(3-(N-hydroxycarbamimidoyl)phenyl)-2-(2,4,6-triisopropylphenylsulfonamido)propanoyl)piperazine-1-carboxylate

RedHill Biopharma Ltd. , an Israeli biopharmaceutical company focused on late clinical-stage drugs for inflammatory and gastrointestinal diseases, including cancer, and WILEX AG , a biopharmaceutical company focused on oncology, based in Munich, Germany, today announced that they have signed an exclusive license agreement for the oncology drug … (more)

http://www.topix.com/de/munich/2014/06/redhill-biopharma-ltd-acquires-phase-2-oncology-drug-mesupron-from-wilex-ag

Upamostat, also known as Mesupron, WX-671, is an orally bioavailable, 3-amidinophenylalanine-derived, second generation serine protease inhibitor prodrug targeting the human urokinase plasminogen activator (uPA) system with potential antineoplastic and antimetastatic activities. After oral administration, serine protease inhibitor WX-671 is converted to the active Nα-(2,4,6-triisopropylphenylsulfonyl)-3-amidino-(L)-phenyla lanine-4-ethoxycarbonylpiperazide (WX-UK1), which inhibits several serine proteases, particularly uPA; inhibition of uPA may result in the inhibition of tumor growth and metastasis. uPA is a serine protease involved in degradation of the extracellular matrix and tumor cell migration and proliferation.

WX-671 (Mesupron) is an orally available prodrug of WX-UK1, a serine protease inhibitor that inhibits uPA as well as other serine proteases. WX-UK1 (Setyono-Han et al., Thromb Haemost 2005) and WX-671 have shown to efficiently reduce primary tumor growth and metastasis formation in a variety of animal models. The proteolytic factor uPA and its inhibitor PAI-1 belong to those biological factors which have provided the highest level of evidence (LOE1) in terms of their prognostic and predictive significance. WX-671 is currently the only drug in Phase II aiming at this target.Results: All 95 patients were accrued between Jun 2007 and Aug 2008. Efficacy is assessed by a central reader at regular intervals based on digital CT images. By end of 2009, 2 patients were still on treatment without signs of progression, 64 patients had died. Preliminary analysis of overall survival showed an increase in overall survival from 10.2 mo (gemcitabine alone) to 13.5 mo for the combination of gemcitabine and WX-671. 1-year survival increased from 37% with gemcitabine to 53% when combined with 400 mg WX- 671. Conclusions: The combination of daily oral WX-671 in combination with weekly i.v. gemcitabine was well tolerated. see asco.com’s website.

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1. Buddy et al, Suppression of Rat Brest Cancer Metastasis and Reduction of Primary Tumor Growth by the Small Synthetic Urokinase Inhibitor WX-UK1. Thromb Haemost. 2005, 93:779-786.

2. Ertongur S, Lang S, Mack B, Wosikowski K, Muehlenweg B, Gires O. Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system. Int J Cancer. 2004, 110(6):815-24.

3. Setyono-Han B, Stürzebecher J, Schmalix WA, Muehlenweg B, Sieuwerts AM, Timmermans M, Magdolen V, Schmitt M, Klijn JG, Foekens JA. Suppression of rat breast cancer metastasis and reduction of primary tumour growth by the small synthetic urokinase inhibitor WX-UK1. Thromb Haemost. 2005, 93(4):779-86.