MK-0429   Click here for help

GtoPdb Ligand ID: 9689

Synonyms: compound 6 [PMID:14561098] [1] | MK-429 | MK0429
Compound class: Synthetic organic
Comment: MK-0429 is an orally active, non-peptide inhibitor/antagonist of αv integrins [1-2,4]. It was initially identified as a clinical lead with potential utility for the prevention and treatment of osteoporosis [1], but has since shown activity in other biological settings. MK-0429 binds to the αv's Arg-Gly-Asp (RGD)-motif binding domain (the RGD-motif is a conserved sequence in proteins that bind to αv integrins), thereby preventing interaction with RGD-containing binding partners such as osteopontin, bone sialoprotein, vitronectin, and fibrinogen.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

MK-0429 is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 8
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 107.89
Molecular weight 439.22
XLogP 1.81
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1ccc(cn1)C(N1CCN(C1=O)CCCc1ccc2c(n1)NCCC2)CC(=O)O
Isomeric SMILES COc1ccc(cn1)[C@@H](N1CCN(C1=O)CCCc1ccc2c(n1)NCCC2)CC(=O)O
InChI InChI=1S/C23H29N5O4/c1-32-20-9-7-17(15-25-20)19(14-21(29)30)28-13-12-27(23(28)31)11-3-5-18-8-6-16-4-2-10-24-22(16)26-18/h6-9,15,19H,2-5,10-14H2,1H3,(H,24,26)(H,29,30)/t19-/m0/s1
InChI Key HGFOOLONGOBCMP-IBGZPJMESA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Hutchinson JH, Halczenko W, Brashear KM, Breslin MJ, Coleman PJ, Duong LT, Fernandez-Metzler C, Gentile MA, Fisher JE, Hartman GD et al.. (2003)
Nonpeptide alphavbeta3 antagonists. 8. In vitro and in vivo evaluation of a potent alphavbeta3 antagonist for the prevention and treatment of osteoporosis.
J Med Chem, 46 (22): 4790-8. [PMID:14561098]
2. Pickarski M, Gleason A, Bednar B, Duong LT. (2015)
Orally active αvβ3 integrin inhibitor MK-0429 reduces melanoma metastasis.
Oncol Rep, 33 (6): 2737-45. [PMID:25872534]
3. Rosenthal MA, Davidson P, Rolland F, Campone M, Xue L, Han TH, Mehta A, Berd Y, He W, Lombardi A. (2010)
Evaluation of the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases.
Asia Pac J Clin Oncol, 6 (1): 42-8. [PMID:20398037]
4. Zhou X, Zhang J, Haimbach R, Zhu W, Mayer-Ezell R, Garcia-Calvo M, Smith E, Price O, Kan Y, Zycband E et al.. (2017)
An integrin antagonist (MK-0429) decreases proteinuria and renal fibrosis in the ZSF1 rat diabetic nephropathy model.
Pharmacol Res Perspect, 5 (5). [PMID:28971604]