UK 356618 (Compound 4j) is a potent and selective inhibitor of matrix metalloprotease-3 (MMP-3) with an IC₅₀ of 5.9 nM. UK 356618 is less potent against MMP-1, MMP-2, MMP-9, MMP-13 and MMP-14 compared with MMP-3^[1]. In Vitro: Inhibition of MMP-3 and selectivity over MMP-2 was remarkably sensitive to the size of the substituent and is clearly optimal for a methyl group (UK 356618, compound 4j). UK 356618 is more widely profiled against other MMPs^[1].
MMP-13 is closely involved in IL-6 or TNF-α increasing tumor metastasis. MMP-13 deficiency abrogate TNF-α effect on lung cancer cell migration. UK 356618 treatment efficiently abolished the effect of TNF-α on cell migration in NCI-H446 cells^[2]. In Vivo: UK 356618 (15 mg/kg; intravenous injection; for 24 h or 7 days; male Wistar rats) treatment at reperfusion significantly reduces MMP3 activity in the brain^[3].