upamostat   Click here for help

GtoPdb Ligand ID: 6497

Synonyms: WX-671
Compound class: Synthetic organic
Comment: Upamostat (WX-671) is an oral serine protease inhibitor prodrug. Its principal molecular target is plasminogen activator, urokinase (uPA; PLAU) [2]. The uPA system plays an important role in tumour invasion and metastasis. The active substance is WX-UK1.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 15
Topological polar surface area 149.02
Molecular weight 629.32
XLogP 6.24
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCOC(=O)N1CCN(CC1)C(=O)C(NS(=O)(=O)c1c(cc(cc1C(C)C)C(C)C)C(C)C)Cc1cccc(c1)C=NNO
Isomeric SMILES CCOC(=O)N1CCN(CC1)C(=O)[C@@H](NS(=O)(=O)c1c(cc(cc1C(C)C)C(C)C)C(C)C)Cc1cccc(c1)/C=N/NO
InChI InChI=1S/C32H47N5O6S/c1-8-43-32(39)37-14-12-36(13-15-37)31(38)29(17-24-10-9-11-25(16-24)20-33-35-40)34-44(41,42)30-27(22(4)5)18-26(21(2)3)19-28(30)23(6)7/h9-11,16,18-23,29,34-35,40H,8,12-15,17H2,1-7H3/b33-20+/t29-/m0/s1
InChI Key CYCFEEXTLQGJEL-XEOXDSMQSA-N
References
1. Ertongur S, Lang S, Mack B, Wosikowski K, Muehlenweg B, Gires O. (2004)
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, 110 (6): 815-24. [PMID:15170662]
2. Froriep D, Clement B, Bittner F, Mendel RR, Reichmann D, Schmalix W, Havemeyer A. (2013)
Activation of the anti-cancer agent upamostat by the mARC enzyme system.
Xenobiotica, 43 (9): 780-4. [PMID:23379481]
3. Heinemann V, Ebert MP, Laubender RP, Bevan P, Mala C, Boeck S. (2013)
Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer.
Br J Cancer, 108 (4): 766-70. [PMID:23412098]
4. Meyer JE, Brocks C, Graefe H, Mala C, Thäns N, Bürgle M, Rempel A, Rotter N, Wollenberg B, Lang S. (2008)
The Oral Serine Protease Inhibitor WX-671 - First Experience in Patients with Advanced Head and Neck Carcinoma.
Breast Care (Basel), 3 (s2): 20-24. [PMID:20824010]
5. Setyono-Han B, Stürzebecher J, Schmalix WA, Muehlenweg B, Sieuwerts AM, Timmermans M, Magdolen V, Schmitt M, Klijn JG, Foekens JA. (2005)
Suppression of rat breast cancer metastasis and reduction of primary tumour growth by the small synthetic urokinase inhibitor WX-UK1.
Thromb Haemost, 93 (4): 779-86. [PMID:15841327]