购物车 
-
GSK 923295
- names：
GSK 923295
- CAS号：
1088965-37-0
MDL Number： MFCD16038931 - MF(分子式)： C32H38ClN5O4 MW(分子量)： 592.13
- EINECS:256-495-9 Reaxys Number:
- Pubchem ID:46898058 Brand:BIOFOUNT
GSK-923295(1088965-37-0)是一种着丝粒相关蛋白E（CENP-E）的新型抗有丝分裂抑制剂，具有潜在的抗癌活性。GSK923295A表现出对实体瘤模型的显着抗肿瘤活性，可在尤因肉瘤，横纹肌肉瘤和横纹肌肉瘤异种移植物中诱导CR。临床研究表明，GSK923295具有与剂量成比例的药代动力学，并具有少量的3级或4级不良事件。观察到的骨髓抑制和神经病的发生率很低。进一步的研究可以更全面地了解GSK923295作为抗增殖剂的潜力。
| 货品编码 | 规格 | 纯度 | 价格 (¥) | 现价(¥) | 特价(¥) | 库存描述 | 数量 | 总计 (¥) |
|---|---|---|---|---|---|---|---|---|
| HCR206409-5mg | 5mg | 97% | ¥ 1662.50 | ¥ 1662.50 | 4-7周 | ¥ 0.00 |
| 中文别名 | GSK 923295(1088965-37-0);GSK923295；GSK 923295；GSK-923295；GSK-923295A; GSK923295A; GSK 923295A。 |
| 英文别名 | GSK 923295(1088965-37-0);GSK923295；GSK 923295；GSK-923295；GSK-923295A; GSK923295A; GSK 923295A。 |
| CAS号 | 1088965-37-0 |
| Inchi | InChI=1S/C32H38ClN5O4/c1-20(2)42-29-13-12-24(16-27(29)33)32(41)35-25(17-34-30(40)19-37(4)5)15-22-8-10-23(11-9-22)28-18-38-14-6-7-26(21(3)39)31(38)36-28/h6-14,16,18,20-21,25,39H,15,17,19H2,1-5H3,(H,34,40)(H,35,41)/t21-,25-/m0/s1 |
| InchiKey | WHMXDBPHBVLYRC-OFVILXPXSA-N |
| 分子式 Formula | C32H38ClN5O4 |
| 分子量 Molecular Weight | 592.13 |
| 溶解度Solubility | 生物体外In Vitro:DMSO溶解度30 mg/mL(50.66 mM;Need ultrasonic)H2O< 0.1 mg/mL(insoluble) |
| 性状 | No data available |
| 储藏条件 Storage conditions | storage at -4℃ (1-2weeks), longer storage period at -20℃ (1-2years) |
GSK-923295(1088965-37-0)实验注意事项：
1.实验前需戴好防护眼镜，穿戴防护服和口罩，佩戴手套，避免与皮肤接触。
2.实验过程中如遇到有毒或者刺激性物质及有害物质产生，必要时实验操作需要手套箱内完成以免对实验人员造成伤害
3.实验后产生的废弃物需分类存储，并交于专业生物废气物处理公司处理，以免造成环境污染
Experimental considerations:
1. Wear protective glasses, protective clothing and masks, gloves, and avoid contact with the skin during the experiment.
2. The waste generated after the experiment needs to be stored separately, and handed over to a professional biological waste gas treatment company to avoid environmental pollution.
Tags:GSK-923295试剂,GSK-923295杂质,GSK-923295中间体,GSK-923295结构式,GSK-923295旋光度,GSK-923295密度,GSK-923295溶解度,GSK-923295闪点,GSK-923295熔点,GSK-923295购买,
| 产品说明 | GSK 923295(1088965-37-0)可以作为中间体及药物杂质使用，该产品非药用，非食用。 |
| Introduction | GSK 923295(1088965-37-0)only use for non-medical purposes in industrial or scientific research, and not for clinical diagnosis and treatment of humans or animals. This product is not medicinal or edible. |
| Application1 | GSK-923295是一种微小的变构着丝粒相关蛋白-E （CENP-E）驱动蛋白ATPase活性抑制剂，作用于人类和犬类此酶，K一世 分别为3.2±0.2 nM和1.6±0.1 nM。 |
| Application2 | |
| Application3 |
GSK-923295(1088965-37-0)药理学：
GSK-923295是一种着丝粒相关蛋白E（CENP-E）的新型抗有丝分裂抑制剂，具有潜在的抗癌活性。GSK923295A表现出对实体瘤模型的显着抗肿瘤活性，可在尤因肉瘤，横纹肌肉瘤和横纹肌肉瘤异种移植物中诱导CR。临床研究表明，GSK923295具有与剂量成比例的药代动力学，并具有少量的3级或4级不良事件。观察到的骨髓抑制和神经病的发生率很低。进一步的研究可以更全面地了解GSK923295作为抗增殖剂的潜力。
GSK923295是CENP-E驱动蛋白运动型ATPase的一流特异性变构抑制剂，Ki为3.2 nM，对突变体I182和T183的作用较小。; IC50值：3.2 nM（Ki）；目标：CENP-E；体外：GSK923295与ATP和微管（MT）均不竞争，抑制CENP-E MT刺激的ATPase活性，Ki为3.2 nM，对其他驱动蛋白。GSK923295抑制无机磷酸盐的释放并稳定CENP-E运动域与微管的相互作用，将ATP促进的CENP-E从MT（koff，MT）的解离速率降低50倍以上。GSK923295导致中期染色体比对失败，并导致有丝分裂停滞。GSK923295是有效的肿瘤细胞生长抑制剂，对于237个肿瘤细胞系，平均GI50为253 nM，中值GI50为32 nM。
GSK-923295是一种着丝粒相关蛋白E（CENP-E）的新型抗有丝分裂抑制剂，具有潜在的抗癌活性。GSK923295A表现出对实体瘤模型的显着抗肿瘤活性，可在尤因肉瘤，横纹肌肉瘤和横纹肌肉瘤异种移植物中诱导CR。临床研究表明，GSK923295具有与剂量成比例的药代动力学，并具有少量的3级或4级不良事件。观察到的骨髓抑制和神经病的发生率很低。进一步的研究可以更全面地了解GSK923295作为抗增殖剂的潜力。
GSK923295是CENP-E驱动蛋白运动型ATPase的一流特异性变构抑制剂，Ki为3.2 nM，对突变体I182和T183的作用较小。; IC50值：3.2 nM（Ki）；目标：CENP-E；体外：GSK923295与ATP和微管（MT）均不竞争，抑制CENP-E MT刺激的ATPase活性，Ki为3.2 nM，对其他驱动蛋白。GSK923295抑制无机磷酸盐的释放并稳定CENP-E运动域与微管的相互作用，将ATP促进的CENP-E从MT（koff，MT）的解离速率降低50倍以上。GSK923295导致中期染色体比对失败，并导致有丝分裂停滞。GSK923295是有效的肿瘤细胞生长抑制剂，对于237个肿瘤细胞系，平均GI50为253 nM，中值GI50为32 nM。
| 警示图 | |
| 危险性 | warning |
| 危险性警示 | Not available |
| 安全声明 | H303吞入可能有害+H313皮肤接触可能有害+H333吸入可能对身体有害 |
| 安全防护 | P264处理后彻底清洗+P280戴防护手套/穿防护服/戴防护眼罩/戴防护面具+P305如果进入眼睛+P351用水小心冲洗几分钟+P338取出隐形眼镜（如果有）并且易于操作,继续冲洗+P337如果眼睛刺激持续+P313获得医疗建议/护理 |
| 备注 | GSK 923295实验过程中防止吸入、食入，做好安全防护 |
| Wood KW, et al. Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44. |
| Mayes PA, et al. Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E (CENP-E) inhibition. Int J Cancer. 2013 Feb 1;132(3):E149-57. |
| Balamuth NJ, et al. Serial transcriptome analysis and cross-species integration identifies centromere-associated protein E as a novel neuroblastoma target. Cancer Res. 2010 Apr 1;70(7):2749-58. |
| Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295 PMID 24900171; ACS medicinal chemistry letters 2010 Apr; 1(1):30-4 Name matches: 3-chloro-4-isopropo |
| Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells PMID 26943579; Oncotarget 2016 Mar; 7(12):14841-56 Name matches: pf-2771 |
GSK-923295(1088965-37-0)参考文献：
1.Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295.
Qian X;McDonald A;Zhou HJ;Adams ND;Parrish CA;Duffy KJ;Fitch DM;Tedesco R;Ashcraft LW;Yao B;Jiang H;Huang JK;Marin MV;Aroyan CE;Wang J;Ahmed S;Burgess JL;Chaudhari AM;Donatelli CA;Darcy MG;Ridgers LH;Newlander KA;Schmidt SJ;Chai D;Colón M;Zimmerman MN;Lad L;Sakowicz R;Schauer S;Belmont L;Baliga R;Pierce DW;Finer JT;Wang Z;Morgan BP;Morgans DJ Jr;Auger KR;Sung CM;Carson JD;Luo L;Hugger ED;Copeland RA;Sutton D;Elliott JD;Jackson JR;Wood KW;Dhanak D;Bergnes G;Knight SD ACS Med Chem Lett. 2010 Jan 19;1(1):30-4. doi: 10.1021/ml900018m. eCollection 2010 Apr 8.
Inhibition of mitotic kinesins represents a novel approach for the discovery of a new generation of anti-mitotic cancer chemotherapeutics. We report here the discovery of the first potent and selective inhibitor of centromere-associated protein E (CENP-E) 3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1-methylethyl)oxy]benzamide (GSK923295; 1), starting from a high-throughput screening hit, 3-chloro-4-isopropoxybenzoic acid 2. Compound 1 has demonstrated broad antitumor activity in vivo and is currently in human clinical trials.
2.Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells.
Kim JH;Lee HS;Lee NC;Goncharov NV;Kumeiko V;Masumoto H;Earnshaw WC;Kouprina N;Larionov V Oncotarget. 2016 Mar 22;7(12):14841-56. doi: 10.18632/oncotarget.7854.
Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" assay). Using this system, anticancer drugs can be easily ranked on by their effect on HAC loss. However, it is problematic to covert this "loss of signal" assay into a high-throughput screen to identify drugs and mutations that increase CIN levels. To address this point, we re-designed the HAC-based assay. In this new system, the HAC carries a constitutively expressed shRNA against the EGFP transgene integrated into human genome. Thus, cells that inherit the HAC display no green fluorescence, while cells lacking the HAC do. We verified the accuracy of this "gain of signal" assay by measuring the level of CIN induced by known antimitotic drugs and added to the list of previously ranked CIN inducing compounds, two newly characterized inhibitors of the centromere-associated protein CENP-E, PF-2771 and GSK923295 that exhibit the highest effect on chromosome instability measured to date.
3.Antitumor activity of an allosteric inhibitor of centromere-associated protein-E.
Wood KW;Lad L;Luo L;Qian X;Knight SD;Nevins N;Brejc K;Sutton D;Gilmartin AG;Chua PR;Desai R;Schauer SP;McNulty DE;Annan RS;Belmont LD;Garcia C;Lee Y;Diamond MA;Faucette LF;Giardiniere M;Zhang S;Sun CM;Vidal JD;Lichtsteiner S;Cornwell WD;Greshock JD;Wooster RF;Finer JT;Copeland RA;Huang PS;Morgans DJ Jr;Dhanak D;Bergnes G;Sakowicz R;Jackson JR Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44. doi: 10.1073/pnas.0915068107. Epub 2010 Feb 18.
Centromere-associated protein-E (CENP-E) is a kinetochore-associated mitotic kinesin that is thought to function as the key receptor responsible for mitotic checkpoint signal transduction after interaction with spindle microtubules. We have identified GSK923295, an allosteric inhibitor of CENP-E kinesin motor ATPase activity, and mapped the inhibitor binding site to a region similar to that bound by loop-5 inhibitors of the kinesin KSP/Eg5. Unlike these KSP inhibitors, which block release of ADP and destabilize motor-microtubule interaction, GSK923295 inhibited release of inorganic phosphate and stabilized CENP-E motor domain interaction with microtubules. Inhibition of CENP-E motor activity in cultured cells and tumor xenografts caused failure of metaphase chromosome alignment and induced mitotic arrest, indicating that tight binding of CENP-E to microtubules is insufficient to satisfy the mitotic checkpoint. Consistent with genetic studies in mice suggesting that decreased CENP-E function can have a tumor-suppressive effect, inhibition of CENP-E induced tumor cell apoptosis and tumor regression.
1.Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295.
Qian X;McDonald A;Zhou HJ;Adams ND;Parrish CA;Duffy KJ;Fitch DM;Tedesco R;Ashcraft LW;Yao B;Jiang H;Huang JK;Marin MV;Aroyan CE;Wang J;Ahmed S;Burgess JL;Chaudhari AM;Donatelli CA;Darcy MG;Ridgers LH;Newlander KA;Schmidt SJ;Chai D;Colón M;Zimmerman MN;Lad L;Sakowicz R;Schauer S;Belmont L;Baliga R;Pierce DW;Finer JT;Wang Z;Morgan BP;Morgans DJ Jr;Auger KR;Sung CM;Carson JD;Luo L;Hugger ED;Copeland RA;Sutton D;Elliott JD;Jackson JR;Wood KW;Dhanak D;Bergnes G;Knight SD ACS Med Chem Lett. 2010 Jan 19;1(1):30-4. doi: 10.1021/ml900018m. eCollection 2010 Apr 8.
Inhibition of mitotic kinesins represents a novel approach for the discovery of a new generation of anti-mitotic cancer chemotherapeutics. We report here the discovery of the first potent and selective inhibitor of centromere-associated protein E (CENP-E) 3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1-methylethyl)oxy]benzamide (GSK923295; 1), starting from a high-throughput screening hit, 3-chloro-4-isopropoxybenzoic acid 2. Compound 1 has demonstrated broad antitumor activity in vivo and is currently in human clinical trials.
2.Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells.
Kim JH;Lee HS;Lee NC;Goncharov NV;Kumeiko V;Masumoto H;Earnshaw WC;Kouprina N;Larionov V Oncotarget. 2016 Mar 22;7(12):14841-56. doi: 10.18632/oncotarget.7854.
Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" assay). Using this system, anticancer drugs can be easily ranked on by their effect on HAC loss. However, it is problematic to covert this "loss of signal" assay into a high-throughput screen to identify drugs and mutations that increase CIN levels. To address this point, we re-designed the HAC-based assay. In this new system, the HAC carries a constitutively expressed shRNA against the EGFP transgene integrated into human genome. Thus, cells that inherit the HAC display no green fluorescence, while cells lacking the HAC do. We verified the accuracy of this "gain of signal" assay by measuring the level of CIN induced by known antimitotic drugs and added to the list of previously ranked CIN inducing compounds, two newly characterized inhibitors of the centromere-associated protein CENP-E, PF-2771 and GSK923295 that exhibit the highest effect on chromosome instability measured to date.
3.Antitumor activity of an allosteric inhibitor of centromere-associated protein-E.
Wood KW;Lad L;Luo L;Qian X;Knight SD;Nevins N;Brejc K;Sutton D;Gilmartin AG;Chua PR;Desai R;Schauer SP;McNulty DE;Annan RS;Belmont LD;Garcia C;Lee Y;Diamond MA;Faucette LF;Giardiniere M;Zhang S;Sun CM;Vidal JD;Lichtsteiner S;Cornwell WD;Greshock JD;Wooster RF;Finer JT;Copeland RA;Huang PS;Morgans DJ Jr;Dhanak D;Bergnes G;Sakowicz R;Jackson JR Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44. doi: 10.1073/pnas.0915068107. Epub 2010 Feb 18.
Centromere-associated protein-E (CENP-E) is a kinetochore-associated mitotic kinesin that is thought to function as the key receptor responsible for mitotic checkpoint signal transduction after interaction with spindle microtubules. We have identified GSK923295, an allosteric inhibitor of CENP-E kinesin motor ATPase activity, and mapped the inhibitor binding site to a region similar to that bound by loop-5 inhibitors of the kinesin KSP/Eg5. Unlike these KSP inhibitors, which block release of ADP and destabilize motor-microtubule interaction, GSK923295 inhibited release of inorganic phosphate and stabilized CENP-E motor domain interaction with microtubules. Inhibition of CENP-E motor activity in cultured cells and tumor xenografts caused failure of metaphase chromosome alignment and induced mitotic arrest, indicating that tight binding of CENP-E to microtubules is insufficient to satisfy the mitotic checkpoint. Consistent with genetic studies in mice suggesting that decreased CENP-E function can have a tumor-suppressive effect, inhibition of CENP-E induced tumor cell apoptosis and tumor regression.
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