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。
αvβ1
1.6 nM (IC
50
, inhibition of fibronectin-binding )
|
αvβ3
2.8 nM (IC
50
, inhibition of vitronectin-binding)
|
αvβ5
0.1 nM (IC
50
, inhibition of vitronectin-binding)
|
αvβ6
0.7 nM (IC
50
, inhibition of LAP-binding)
|
αvβ8
0.5 nM (IC
50
, inhibition of LAP-binding)
|
α5β1
12.2 nM (IC
50
, inhibition of fibronectin-binding)
|
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.
Animal Model:
|
B6D2F1 hybrid female mice
|
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]
.
|