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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2D Structure
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Physico-chemical Properties
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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
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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
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]