UK-370106

UK-370106 is a potent and highly selective MMP-3 (IC₅₀ of 23 nM) and MMP-12 (IC₅₀ of 42 nM) inhibitor with >1200-fold higher potency than MMP-1, MMP-2, MMP-9, and MMP-14, and about 100-fold than MMP-13 and MMP-8. UK-370106 potently inhibits cleavage of [³H]-fibronectin by MMP-3 (IC₅₀ of 320 nM) and has little effect on keratinocyte migration in vitro^[1][2]. In Vitro: The potency of UK-370106 (compound 7) for the inhibition of MMP-13 is 2.3 µM, some 100-fold less potent than its inhibition of MMP-3. UK-370106 is found to be inactive (IC₅₀ > 100 µM) vs zinc metalloproteases PCP and TACE and possesses the following inhibitory potencies vs MMP-2 (IC₅₀ of 34.2 µM), MMP-7 (IC₅₀ of 5.8 µM), MMP-8 (IC₅₀ of 1.75 µM), MMP-9 (IC₅₀ of 30.4 µM) and MMP-14 (IC₅₀ of 66.9 µM)^[1].
UK-370106 potently inhibits cleavage of [³H]-fibronectin by MMP-3 (IC₅₀ of 320 nM) but does not inhibit cleavage of [³H]-gelatin by either MMP-2 or -9 up to the highest concentration tested (100 µM)^[1].
UK-370106 is not cytotoxic to, nor affected proliferation of, fibroblasts, keratinocytes, or endothelial cells at 50-100 µM in vitro^[1]. In Vivo: Following iv (rat; 2 mg/kg) or topical administration to dermal wounds (rabbit), UK-370106 (compound 7) is cleared rapidly (t_1/2 = 23 min) from plasma, but slowly (t_1/2 approximately 3 days) from dermal tissue. In a model of chronic dermal ulcers, topical administration of UK-370106 for 6 days substantially inhibits MMP-3 ex vivo^[1].