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AG14361
  • AG14361

AG14361

價格 詢價
包裝 1EA
最小起訂量 1EA
發(fā)貨地 浙江
更新日期 2022-11-03

產(chǎn)品詳情

英文名稱:AG14361
規(guī)格: (5mg/100mg/224mg)英文名: AG14361; AG-14361; AG 14361.
供應(yīng)商: 美國CAS號: 328543-09-5
保存條件: 2 years -20°C Powder, 2 weeks4°C in DMSO,6 months-80°C in DMSO保質(zhì)期: 2 years -20°C Powder, 2 weeks4°C in DMSO,6 months-80°C in DMSO
貨號: ONI-171175數(shù)量: 674.0
2022-11-03 AG14361 AG14361 1EA/RMB
AG14361 is a potent inhibitor of PARP1 with Ki of <5 nM. It is at least 1000-fold more potent than the benzamides. IC50 Value: <5 nM( Ki) Target: PARP1 in vitro: AG14361 is at least 1000-fold more potent than the benzamides. The IC50 for AG14361 is 29 nM in permeabilized SW620 cells and 14 nM in intact SW620 cells. Crystallographic analysis of AG14361 bound to the catalytic domain of chicken PARP-1 shows that the tricyclic ring system of AG14361 is located in a pocket composed of amino acid residues Trp861, His862, Gly863, Tyr896, Phe897, Ala898, Lys903, Ser904, Tyr907, and Glu988. AG14361 forms important hydrogen bonds with Ser904 and Gly863 and a water-mediated hydrogen bond with Glu988. AG14361-induced growth inhibition is not attributed to PARP-1-related effects because maximal PARP-1 inhibition is observed at much lower concentrations (≤1 μM) than the GI50. AG14361 at 0.4 μM does not affect cancer cell gene expression or growth, but it increases the antiproliferative activity of temozolomide and topotecan, and inhibits recovery from potentially lethal γ-radiation damage in LoVo cells by 73%. In addition, 0.4 μM AG14361 does not substantially alter gene expression as shown by microarray analysis. A 17-hour exposure of A549 cells to 0.4 μM AG14361 does not change the expression of the 6800 genes. in vivo: AG14361 treatment before irradiation statistically significantly increases the sensitivity to radiation therapy of mice bearing LoVo xenografts. AG14361 statistically significantly increases blood flow in xenografts and thus potentially increases drug delivery to tumor xenografts. In vivo, nontoxic doses of AG14361 increases the delay of LoVo xenograft growth induced by irinotecan, x-irradiation, or temozolomide by 2- to 3-fold. Coadministration of AG14361 with temozolomide statistically significantly increases temozolomide activity against LoVo xenografts, with the tumor growth delay being increased from 3 days to 9 days by AG14361 at 5 mg/kg and to 10 days by AG14361 at 15 mg/kg. The combination of AG14361 and temozolomide causes complete regression of SW620 xenograft tumors. PARP-1 activity, detected by pharmacodynamic assay, in SW620 xenografts is inhibited by more than 75% for at least 4 hours after intraperitoneal administration of AG14361 (10 mg/kg), consistent with the concentration of AG14361 persisting in the tumor.
溫馨提示:不可用于臨床治療。
關(guān)鍵字: AG14361;生物化學(xué)

公司簡介

浙江昂拓萊司生物技術(shù)股份有限公司(Ontores Biotech, 鴻拓生物),創(chuàng)立于2009年, 總部位于杭州海創(chuàng)園。公司研發(fā)團隊由十多名海內(nèi)外知名院校的博士/博后帶領(lǐng),擁有多年的多肽藥物開發(fā)經(jīng)驗, 已成為世界領(lǐng)先的多肽服務(wù)公司。除了常規(guī)多肽類產(chǎn)品,我們還能提供各種特殊修飾肽,包括:糖肽、各類多肽探針、MAPS復(fù)合抗原肽、點擊化學(xué)肽、PEG修飾肽、環(huán)肽、訂書肽、細(xì)胞穿膜肽、 抗菌肽等等應(yīng)用于各類藥物研究。此外,昂拓萊司還可提供多肽藥物技術(shù)開發(fā)一體化解決方案,從技術(shù)研發(fā)到臨床醫(yī)藥產(chǎn)品小試中試及商業(yè)化規(guī)模的多肽藥物生產(chǎn)需求,幫助我們的合作伙伴實現(xiàn)探索新藥的無限可能。
成立日期 注冊資本
員工人數(shù) 年營業(yè)額
主營行業(yè) 合成材料中間體 經(jīng)營模式 工廠
  • 鴻拓生物技術(shù)股份有限公司
非會員
  • 公司成立:暫無
  • 注冊資本:暫無
  • 企業(yè)類型:暫無
  • 主營產(chǎn)品:暫無
  • 公司地址:余杭區(qū)倉前街道文一西路1378號F座1樓
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