| Bioactivity | 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]. | |||||||||
| Invitro | 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]. Animal Model: | |||||||||
| Name | UK 356618 | |||||||||
| CAS | 230961-08-7 | |||||||||
| Formula | C34H43N3O4 | |||||||||
| Molar Mass | 557.72 | |||||||||
| Appearance | Solid | |||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | |||||||||
| Storage |
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| Reference | [1]. Fray MJ, et al. Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (stromelysin-1). Bioorg Med Chem Lett. 2001 Feb 26;11(4):571-4. [2]. Yan HQ, et al. Ataxia-telangiectasia mutated activation mediates tumor necrosis factor-alpha induced MMP-13 up-regulation and metastasis in lung cancer cells. Oncotarget. 2016 Sep 20;7(38):62070-62083. [3]. Hafez S, et al. Matrix Metalloprotease 3 Exacerbates Hemorrhagic Transformation and Worsens Functional Outcomes in Hyperglycemic Stroke. Stroke. 2016 Mar;47(3):843-51. |