EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73452_C
细胞周期蛋白/CDK通路抑制剂；抑制CDK1和CDK2
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总览
SU9516是细胞周期依赖性蛋白激酶（CDK）的特异性抑制剂，包括CDK2、CDK1和CDK4（作用程度较低），IC₅₀值分别为22、40和200 nM（Lane et al.）。它竞争性地结合CDK2和CDK1的ATP结合位点（Moshinsky et al.）。SU9516具有高选择性，并且不抑制PKC、p38 MAPK、PDGFR或EGFR（IC₅₀> 10 μM；Lane et al.）。
癌症研究
·通过抑制视网膜母细胞瘤蛋白（Rb）磷酸化，降低人结肠癌细胞系RKO和SW480的增殖，导致Rb/E2F增加、细胞周期停滞和随后的细胞凋亡（Lane et al.; Yu et al.）。
·通过下调U937、Jurkat和HL-60白血病或淋巴瘤细胞系中的抗凋亡蛋白MCL-1的转录，诱导线粒体损伤、胱天蛋白酶活化和随后的细胞凋亡（Gao et al.）。
·单独或与紫杉醇搭配使用，在炎性乳腺癌细胞系SUM149PT中诱导细胞凋亡（Opyrchal et al.）。
细胞类型
癌细胞及细胞系，白血病/淋巴瘤细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
研究领域
癌症
CAS 编号
377090-84-1
化学式
C₁₃H₁₁N₃O₂
纯度
≥98%
通路
细胞周期蛋白/CDK
靶点
CDK1，CDK2
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
相关材料与文献
技术资料 (2)
文献 (5)
A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells.
Cancer research 2001
Abstract
Recent studies have indicated that the development of cyclin-dependent kinase (cdk)2 inhibitors that deregulate E2F are a plausible pharmacological strategy for novel antineoplastic agents. We show here that 3-[1-(3H-Imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516),a novel 3-substituted indolinone compound,binds to and selectively inhibits the activity of cdk2. This inhibition results in a time-dependent decrease (4-64%) in the phosphorylation of the retinoblastoma protein pRb,an increase in caspase-3 activation (5-84%),and alterations in cell cycle resulting in either a G(0)-G(1) or a G(2)-M block. We also report here cell line differences in the cdk-dependent phosphorylation of pRb. These findings demonstrate that SU9516 is a selective cdk2 inhibitor and support the theory that compounds that inhibit cdk2 are viable resources in the development of new antineoplastic agents.
SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells.
Biochemical pharmacology 2002
Abstract
The E2F family plays a critical role in the expression of genes required for entry into and progression through S phase. E2F-mediated transcription is repressed by the tumor suppressor retinoblastoma protein (pRb),which results in sequestration of E2F in a multiprotein complex that includes pRb. Derepression of E2F results from a series of complex phosphorylation events mediated by cyclin D/cdk4 and cyclin E/cdk2. We have employed a novel 3-substituted indolinone compound,3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516),which selectively inhibits cdk2 activity (Lane et al.,Cancer Res 2001;61:6170-7) to investigate these events. Electrophoretic mobility gel shift assays were performed on SU9516-treated and -untreated HT-29,SW480,and RKO human colon cancer cell extracts. Treatment with 5 microM SU9516 prevented dissociation of pRb from E2F1 in all cell lines (HT-29textgreaterRKOtextgreaterSW480). Treatment effects were time-dependent,demonstrating greater inhibition at 48 hr versus 24hr in HT-29 cells. Furthermore,E2F species were sequestered in complexes with p107,p130,DP-1,and cyclins A and E. After a 24-hr treatment with 5 microM SU9516,cyclin D1 and cdk2 levels decreased by 10-60%. These findings delineate a previously undescribed mechanism for SU9516-mediated cell growth arrest through down-regulation of cyclin D1,inhibition of cdk2 levels and activity,and pan-sequestration of E2F.
SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2.
Biochemical and biophysical research communications 2003
Abstract
SU9516 is a 3-substituted indolinone compound with demonstrated potent and selective inhibition toward cyclin dependent kinases (cdks). Here,we describe the kinetic characterization of this inhibition with respect to cdk2,1,and 4,along with the crystal structure in complex with cdk2. The molecule is competitive with respect to ATP for cdk2/cyclin A,with a K(i) value of 0.031 microM. Similarly,SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner,although at a 2- to 8-fold reduced potency. In contrast,the compound exhibited non-competitive inhibition with respect to ATP toward cdk4/cyclin D1,with a 45-fold reduced potency. The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. This study should aid in the development of more potent and selective cdk inhibitors for potential therapeutic agents.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 377090-84-1 |
| Chemical Formula | C₁₃H₁₁N₃O₂ |
| 纯度 | ≥ 98% |
| Target | CDK1, CDK2 |
| Pathway | Cyclin/CDK |
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