| Identification | Back Directory | [Name]
L-000845704 | [CAS]
227963-15-7 | [Synonyms]
MK-0429
L-000845704
HGFOOLONGOBCMP-IBGZPJMESA-N
3-Pyridinepropanoic acid, 6-methoxy-β-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]-1-imidazolidinyl]-, (βS)- | [Molecular Formula]
C23H29N5O4 | [MDL Number]
MFCD27665469 | [MOL File]
227963-15-7.mol | [Molecular Weight]
439.51 |
| Chemical Properties | Back Directory | [Melting point ]
122 °C | [Boiling point ]
735.5±60.0 °C(Predicted) | [density ]
1.36±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 250 mg/mL (568.82 mM) | [form ]
Solid | [pka]
4.19±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
MK-0429 (L-000845704) is an orally active, potent, selective and nonpeptide pan-integrin antagonist with IC50 values of 1.6 nM, 2.8 nM, 0.1 nM, 0.7 nM, 0.5 nM and 12.2 nM for αvβ1, αvβ3, αvβ5, αvβ6, αvβ8 and α5β1, respectively[1][2][3]. | [in vivo]
MK-0429 (100 or 300 mg/kg, p.o., twice daily b.i.d., 2 weeks) reduces metastatic tumor colony formation and area in the lungs. MK-0429 is safe and efficacious in significantly decreasing melanoma metastasis in the lungs[1]. | Animal Model: | B6D2F1 hybrid female mice[2] | | Dosage: | 100 or 300 mg/kg | | Administration: | P.o., twice daily (b.i.d.), 2 weeks | | Result: | MK-0429 at 100 and 300 mg/kg reduced the number of metastatic tumor colonies by 64 and 57%, respectively, and the high dose also reduced the tumor area by 60% as compared to the vehicle[2].
|
| [IC 50]
αvβ1: 1.6 nM (IC50, inhibition of fibronectin-binding ); αvβ3: 2.8 nM (IC50, inhibition of vitronectin-binding); αvβ5: 0.1 nM (IC50, inhibition of vitronectin-binding); αvβ6: 0.7 nM (IC50, inhibition of LAP-binding); αvβ8: 0.5 nM (IC50, inhibition of LAP-binding); α5β1: 12.2 nM (IC50, inhibition of fibronectin-binding) | [storage]
Store at -20°C | [References]
[1] Hutchinson JH, et al. 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. 2003 Oct 23;46(22):4790-8. DOI:10.1021/jm030306r
[2] Pickarski M, et al. Orally active αvβ3 integrin inhibitor MK-0429 reduces melanoma metastasis. Oncol Rep. 2015 Jun;33(6):2737-45. DOI:10.3892/or.2015.3910
[3] Xiaoyan Zhou, et al. An integrin antagonist (MK-0429) decreases proteinuria and renal fibrosis in the ZSF1 rat diabetic nephropathy model. Pharmacol Res Perspect. 2017 Oct;5(5):e00354. DOI:10.1002/prp2.354 |
|
|