MK-0429 (L-000845704) 是可口服，高效，选择性，非多肽整合素泛拮抗剂，对αvβ1、αvβ3、αvβ5、αvβ6、αvβ8 和 α5β1 的 IC5 0 值分别为1.6 nM、2.8 nM、0.1 nM、0.7 nM、0.5 nM 和 12.2 nM。
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αvβ1
1.6 nM (IC
50
, inhibition of fibronectin-binding )
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αvβ3
2.8 nM (IC
50
, inhibition of vitronectin-binding)
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αvβ5
0.1 nM (IC
50
, inhibition of vitronectin-binding)
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αvβ6
0.7 nM (IC
50
, inhibition of LAP-binding)
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αvβ8
0.5 nM (IC
50
, inhibition of LAP-binding)
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α5β1
12.2 nM (IC
50
, inhibition of fibronectin-binding)
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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.
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Animal Model:
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B6D2F1 hybrid female mice
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Dosage:
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100 or 300 mg/kg
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Administration:
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P.o., twice daily (b.i.d.), 2 weeks
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Result:
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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]
.
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