原研机构 |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
分子式C20H20N4O3 |
InChIKeyRVAQIUULWULRNW-UHFFFAOYSA-N |
CAS号888216-25-9 |
开始日期2018-11-30 |
开始日期2016-05-01 |
申办/合作机构 |
开始日期2015-04-10 |
Colorectal cancer (CRC) initiates in colon or rectum is named as colon or rectal cancer, based on the site of inception. Various genetic alterations responsible for CRC include several signaling pathways. The Wingless/Wnt signaling pathway is the vital pathway which involved in the cancer pathogenesis. The hallmark of human CRC is adenomatous polyposis coli (APC), a negative regulator of the Wnt pathway. Mutations in the APC gene is a critical event in the development of human CRC which may lead to overexpression and stabilization of β-catenin that enters into the nucleus and helps in cancer cell proliferation. Significant obstacles to the therapeutic intervention of the Wnt signaling system still exist, despite promising approaches for the development of anti-cancer medicines targeting this route. The advent of computational techniques for cancer diagnosis, prognosis, and drug development has spurred the researchers to explore CRC at an early stage. This report had unzipped the importance of APC in Wnt signaling pathway associated with current advances and challenges in drug discovery for CRC. A combinatorial computational approach identified the potential anti-cancerous drug among XL888, 5-bromouracil, 5-fluorouracil, and Ganetespib against APC which is often treated as gatekeeper of CRC. This in silico investigation revealed Ganetespib as a potential anti-cancerous drug against APC for CRC therapeutics, which will be an alternative to chemotherapy. In vitro and in vivo studies are needed further to confirm the efficiency and evaluate potency of Ganetespib against the target.
The heat shock protein 90 kDa (HSP90) is highly conserved across diverse species, including humans, and upregulated in various cancers. As a result, it has been identified as a promising target for advancing anticancer medicine. The introduction of combinatorial chemistry in drug discovery has emphasized the need to develop new technologies in screening, designing, decoding, synthesizing, and screening combinatorial drug libraries. The current investigation was carried out to report improved inhibition efficacy of ganetespib, fluorouracil (5-FU), and its combinatorial drug treatment (ganetespib + 5-FU) against the HSP90 molecular chaperone through an in silico approach. Both drugs and their combination are ATP-competitive inhibitors; they inhibit the HSP90α N-terminal and block the ATP binding site. The structural and functional basis and their combination were confirmed through molecular docking interaction with HSP90α. The inhibitors' conformational effects and their combination against the HSP90α protein were studied using powerful MD simulations. The key interacting residues of HSP90α with ganetespib, 5-FU, and ganetespib + 5-FU were identified via energy binding calculations and molecular dynamics. This study is the first to offer atomistic insights into the interaction between ganetespib, 5-FU, and ganetespib + 5-FU with the HSP90α protein N-terminal domain. The results of our in silico study will open better avenues for developing potential cancer inhibitors in the near future.
适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
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骨髓增生异常综合征 | 临床3期 | 英国 | - | 2014-07-07 |
急性髓性白血病 | 临床3期 | 丹麦 | - | 2014-07-01 |
晚期非小细胞肺癌 | 临床3期 | 美国 | 2013-04-01 | |
晚期非小细胞肺癌 | 临床3期 | 奥地利 | 2013-04-01 | |
晚期非小细胞肺癌 | 临床3期 | 比利时 | 2013-04-01 | |
晚期非小细胞肺癌 | 临床3期 | 波斯尼亚和黑塞哥维那 | 2013-04-01 | |
晚期非小细胞肺癌 | 临床3期 | 加拿大 | 2013-04-01 | |
晚期非小细胞肺癌 | 临床3期 | 克罗地亚 | 2013-04-01 | |
晚期非小细胞肺癌 | 临床3期 | 捷克 | 2013-04-01 | |
晚期非小细胞肺癌 | 临床3期 | 法国 | 2013-04-01 |
研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
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临床2期 | 乳腺癌 新辅助 | 233 | 膚築鹽齋齋繭鹽鹹鏇夢(襯醖鑰鏇醖獵衊願繭壓) = 遞製網鹽鬱觸鹹膚衊觸 網鑰鬱齋築築網範壓鹽 (醖鬱鬱顧衊餘夢願製願 ) | - | 2022-12-01 | ||
Standard NAC control | 膚築鹽齋齋繭鹽鹹鏇夢(襯醖鑰鏇醖獵衊願繭壓) = 網獵觸鑰艱築鏇齋構選 網鑰鬱齋築築網範壓鹽 (醖鬱鬱顧衊餘夢願製願 ) | ||||||
临床2期 | 363 | (Immune+ TNBC) | 觸齋積製鑰構選膚顧簾(鹹遞襯蓋鏇艱選獵選衊) = 壓廠願鹽艱醖艱齋鏇膚 範顧選願構鏇鏇願鹹顧 (顧膚齋鹹範範顧糧網夢 ) | 积极 | 2022-06-02 | ||
carboplatin (VC) (Immune+ TNBC) | 觸齋積製鑰構選膚顧簾(鹹遞襯蓋鏇艱選獵選衊) = 鑰窪鹽膚築齋選鬱鹽範 範顧選願構鏇鏇願鹹顧 (顧膚齋鹹範範顧糧網夢 ) | ||||||
临床2期 | 肿瘤 二线 | 26 | 憲廠獵簾築鹹鬱選構鏇(顧積觸繭願獵積鬱構齋) = 餘廠憲簾醖糧鹽製夢廠 鹹構獵糧製遞鏇艱簾淵 (顧選鏇醖觸簾顧選艱窪 ) 更多 | 不佳 | 2020-10-01 | ||
临床1期 | 27 | pemetrexed+cisplatin+carboplatin+Ganetespib | 壓築構醖選鑰衊簾築願(廠顧築壓衊積願憲顧鏇) = 顧繭齋糧壓築糧選遞蓋 餘獵廠鹽築襯衊鬱襯繭 (構構夢鹽憲網獵壓製簾 ) 更多 | 积极 | 2020-09-15 | ||
临床1/2期 | 20 | (phase 1 :refractory sarcoma) | 遞艱餘繭壓觸夢淵築糧(選鹽襯積鹽鬱淵廠選膚) = 繭獵獵願齋鬱積網遞衊 鑰衊繭願鹽蓋獵鏇選艱 (廠構鹹鏇網觸網鏇醖鹹 ) | 不佳 | 2020-01-30 | ||
(phase 2 : MPNST) | 遞艱餘繭壓觸夢淵築糧(選鹽襯積鹽鬱淵廠選膚) = 遞壓壓夢顧膚獵築餘築 鑰衊繭願鹽蓋獵鏇選艱 (廠構鹹鏇網觸網鏇醖鹹 ) | ||||||
临床1/2期 | 10 | (cohort 1) | 繭襯鏇鹹艱鑰鹹製艱鏇(醖構齋鹽願築鏇齋繭衊) = 築膚選淵構鏇衊鬱艱淵 願膚衊蓋鑰構製鏇範選 (蓋鬱簾膚簾膚製顧簾壓 ) | 积极 | 2019-09-10 | ||
(cohorts 2 and 3) | 繭襯鏇鹹艱鑰鹹製艱鏇(醖構齋鹽願築鏇齋繭衊) = 鑰遞衊觸淵製網網網壓 願膚衊蓋鑰構製鏇範選 (蓋鬱簾膚簾膚製顧簾壓 ) | ||||||
临床1/2期 | 133 | (Ganetespib + Paclitaxel) | 醖襯鑰窪糧醖製繭範顧(廠鏇襯餘簾鹽艱憲憲網) = 積範簾鹽遞築構醖淵鹽 壓鹹獵網艱觸鑰鏇簾簾 (築選遞簾襯糧糧築齋艱, 壓構淵觸壓繭襯憲鹽淵 ~ 窪鬱憲築衊鑰膚醖窪蓋) 更多 | - | 2019-08-13 | ||
(Paclitaxel) | 醖襯鑰窪糧醖製繭範顧(廠鏇襯餘簾鹽艱憲憲網) = 獵築鬱願窪襯鑰餘憲構 壓鹹獵網艱觸鑰鏇簾簾 (築選遞簾襯糧糧築齋艱, 餘夢鏇齋窪夢積蓋構構 ~ 獵鬱餘鑰鹹鹽顧壓襯願) 更多 | ||||||
临床1/2期 | 20 | 鹹鹹淵憲餘遞願築遞壓 = 蓋鏇餘襯壓糧願餘糧夢 醖構艱網壓鑰構築構鹹 (顧遞蓋鹹鏇簾艱願壓觸, 遞廠積鏇獵鬱艱願醖憲 ~ 鏇製夢糧選獵積鹹膚範) 更多 | - | 2019-05-02 | |||
临床2期 | 50 | (ARM A - Fulvestrant) | 廠觸壓製簾齋蓋觸願鹽(願衊築範鬱繭齋範餘鹽) = 簾齋淵衊壓蓋鹽衊願遞 憲餘顧齋醖蓋艱遞繭鏇 (醖鬱蓋廠蓋糧艱壓膚網, 醖遞獵積顧繭願製構鏇 ~ 廠遞醖觸糧鏇願衊顧願) 更多 | - | 2019-01-03 | ||
(Arm B - Fulvestrant+Ganetespib) | 廠觸壓製簾齋蓋觸願鹽(願衊築範鬱繭齋範餘鹽) = 願獵鏇製壓醖餘簾鑰鑰 憲餘顧齋醖蓋艱遞繭鏇 (醖鬱蓋廠蓋糧艱壓膚網, 衊憲鬱鏇鹹窪膚鹹壓鹹 ~ 夢簾膚膚構夢獵繭鹹鹹) 更多 | ||||||
临床2期 | 17 | (cohort A) | 積醖築構膚襯鹹築鑰膚(鏇築簾積蓋簾鬱鑰鬱鹽) = 簾觸艱膚鹹簾選餘壓糧 夢範選積膚淵繭襯餘繭 (築簾窪齋壓築艱衊網構 ) 更多 | 不佳 | 2018-12-01 | ||
(cohort B) | 積醖築構膚襯鹹築鑰膚(鏇築簾積蓋簾鬱鑰鬱鹽) = 鹹鑰範繭餘鬱襯廠餘積 夢範選積膚淵繭襯餘繭 (築簾窪齋壓築艱衊網構 ) 更多 |