S 3304

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Chemical Structure| 203640-27-1 同义名 : -
CAS号 : 203640-27-1
货号 : A123766
分子式 : C24H20N2O4S2
纯度 : 98%+
分子量 : 464.56
MDL号 : MFCD22200275
存储条件：

Pure form Keep in dark place, inert atmosphere, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 Matrix metalloproteinases (MMPs) are a group of calcium-dependent zinc-endopeptidases engaged in the degradation and remodeling of extracellular matrix. S-3304 is a non-cytotoxic and orally-active inhibitor for MMP-2 and MMP-9, but not MMP-1, MMP-3 and MMP-7[1]. S-3304 completely inhibited the gelatinase activity of MMP-2 and MMP-9 derived from human tumor cells. In mice implanted with HT1080 human fibrosarcoma cells-filled chamber, oral administration of S-3304 (20 and 200 mg/kg, b.i.d) suppressed tumor-induced angiogenesis as shown as decreased number and vascular area of vessels beneath the cutaneous muscle[2]. In the metabolism and pharmacokinetic studies of S-3304, the plasma radioactivity was abruptly elevated by orally administration of [14C]-S-3304 with Tmax of 1.5 hr in rats and 0.6 hr in mice, and eliminated with T1/2 of 3.5 hr in rats and 5.7 hr in mice. The dose-linearity of AUC after the oral administration of S-3304 was found at the doses of 30 mg/kg in rats and 10 mg/kg in mice. The absolute bioavailability of S-3304 was 32% in rats and 34% in mice[3].
作用机制 S-3304 is a D-tryptophan derivative that potently inhibits MMP-2 and MMP-9. The inhibitory activity are greatly affected by the structure of sulfonamide moiety in MMPs[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.22mL

10.76mL

2.15mL

1.08mL

21.53mL

4.31mL

2.15mL
参考文献

[1]Chiappori AA, Eckhardt SG, Bukowski R, Sullivan DM, Ikeda M, Yano Y, Yamada-Sawada T, Kambayashi Y, Tanaka K, Javle MM, Mekhail T, O'bryant CL, Creaven PJ. A phase I pharmacokinetic and pharmacodynamic study of s-3304, a novel matrix metalloproteinase inhibitor, in patients with advanced and refractory solid tumors. Clin Cancer Res. 2007 Apr 1;13(7):2091-9.

[2]In vitro pharmacological profiles and in vivo anti-angiogenesis activity of S-3304, a novel matrix metalloproteinase inhibitor

[3]Non-clinical assessments of drug metabolism and pharmacokinetics of S-3304, a matrix metalloproteinase inhibitor

[4]Tamura Y, Watanabe F, Nakatani T, Yasui K, Fuji M, Komurasaki T, Tsuzuki H, Maekawa R, Yoshioka T, Kawada K, Sugita K, Ohtani M. Highly selective and orally active inhibitors of type IV collagenase (MMP-9 and MMP-2): N-sulfonylamino acid derivatives. J Med Chem. 1998 Feb 12;41(4):640-9.