NSC 663284

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NSC 663284

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

包装:	10mg
市场价:	1575元

产品介绍

NSC 663284 (DA-3003-1) 是一种有效的、细胞可渗透的、不可逆的 Cdc25 双特异性磷酸酶抑制剂，对 Cdc25B2 的 IC50 为 0.21 μM。 NSC 663284 对 Cdc25A、Cdc25B(2) 和 Cdc25C 表现出混合竞争动力学，Ki 值分别为 29、95 和 89 nM。 NSC 663284 通过与催化 SET 结构域的直接相互作用（Kd 为 370 nM）抑制 NSD2（IC50 为 170 nM）。

Animal experiment:

Mice: C.B.-17 SCID mice bearing HT29 human colon carcinoma xenografts are stratified into the following groups of 9-10 animals: Control, vehicle control, positive control (gemcitabine, 50 mg/kg/dose i.v.), NSC 663284 at the following doses: 2, 3 or 5 mg/kg/dose i.v.. The mice are dosed every 4 days for 6 doses, and body weights and tumor volumes are recorded twice weekly. Tumors are measured with calipers, and tumor volumes are calculated. Mice are followed for 3 weeks following the completion of the dosing to monitor tumor regrowth. In a second study, C.B.-17 SCID mice bearing MDA-MB-435 human breast cancer xenografts are stratified to the same treatment groups, except that paclitaxel at 20 mg/kg i.v. every 7 days is used as the positive control[2].

产品描述

NSC 663284 is a potent, cell-permeable, and irreversible Cdc25 dual specificity phosphatase inhibitor, has an IC50 for Cdc25B2 of 0.21 μM. NSC 663284 exhibits mixed competitive kinetics against Cdc25A, Cdc25B(2), and Cdc25C with Ki values of 29, 95, and 89 nM, respectively[1].

NSC 663284 (3-100μM; 48 hours) has a mean IC50 value in the NCI 60 Cell human tumor panel of 1.5 ± 0.6 μM, has IC50 values of 0.2 μM in human breast cancer MDA-MB-435 and MDA-N cells, has an IC50 value of 1.7 μM in human breast MCF-7 cells in culture[1].NSC 663284 has relative IC50 values for Cdc25B2 (IC50=0.21 μM) are 20- and 450-fold lower than for VHR (IC50=4.0 μM) or PTP1B (IC50>4.0 μM), respectively[1].

NSC 663284 (intravenous injection; 2, 3, and 5mg/kg) inhibits the growth of subcutaneous human colon HT29 xenografts in SCID mice. After a single dose of 5 mg/kg, NSC 663284 is not detectable in plasma or tissues beyond 5 min. Following NSC 663284 treatment of tumor-bearing SCID mice, reduces glutathione concentrations in HT29 tumor are decreased to a greater extent and remained decreased for longer than the reduced glutathione concentrations in liver and kidneys[2].

References:
[1]. Lazo JS, et al. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25. J Med Chem. 2001 Nov 22;44(24):4042-9.
[2]. Guo J, et al. Pharmacology and antitumor activity of a quinolinedione Cdc25 phosphatase inhibitor DA3003-1 (NSC 663284). Anticancer Res. 2007 Sep-Oct;27(5A):3067-73.