更新于：2024-07-05
Bemcentinib
更新于：2024-07-05
概要
基本信息
在研机构 |
非在研机构- |
最高研发阶段临床2/3期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评快速通道 (美国)、孤儿药 (美国) |
结构
分子式C30H34N8 |
InChIKeyKXMZDGSRSGHMMK-VWLOTQADSA-N |
CAS号1037624-75-1 |
关联
16
项与 Bemcentinib 相关的临床试验Phase 1b/2a Safety and Tolerability Study of Bemcentinib With Pembrolizumab/Carboplatin/Pemetrexed in Subjects With Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/With a STK11 Mutation
A Phase 1, Open-label, Nonrandomized Study to Investigate the Mass Balance Recovery and Metabolic Profile of 14C-bemcentinib Following Single Oral Administration in Healthy Male Subjects
Efficacy and Safety of AXL-Inhibitor bemcentinib for the Treatment of Moderate COVID-19 (AXL-SolidAct) - AXL-SolidAct
100 项与 Bemcentinib 相关的临床结果
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100 项与 Bemcentinib 相关的转化医学
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100 项与 Bemcentinib 相关的专利（医药）
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129
项与 Bemcentinib 相关的文献（医药）2024-03-08JCI insight
AXL inhibition suppresses early allograft monocyte-to-macrophage differentiation and prolongs allograft survival.
Article
作者: Xiang, Catherine ; Souma, Tomokazu ; Dilts, Miriam E ; Kwun, Jean ; Tunbridge, Matthew ; Jordan, Collin Z ; Thorp, Edward B ; Husain, Irma ; Kitai, Hiroki ; Abe, Koki ; Luo, Xunrong ; Fay, Olivia K
Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages to promote allograft inflammation. However, factors that drive their differentiation to inflammatory macrophages are not understood. Here, we show that the receptor tyrosine kinase AXL was a key driver of early intragraft differentiation of recipient infiltrating monocytes to inflammatory macrophages in the presence of allogeneic stimulation and cell-to-cell contact. In this context, the differentiated inflammatory macrophages were capable of efficient alloantigen presentation and allostimulation of T cells of the indirect pathway. Consequently, early and transient AXL inhibition with the pharmacological inhibitor bemcentinib resulted in a profound reduction of initial allograft inflammation and a significant prolongation of allograft survival in a murine heart transplant model. Our results support further investigation of AXL inhibition as part of an induction regimen for transplantation.
2023-12-01Acta pharmaceutica Sinica. B
Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors
Article
作者: Liu, Hong ; Geng, Meiyu ; Liang, Xuewu ; Zhang, Dong ; Fang, Feifei ; Wang, Danyi ; Ai, Jing ; Li, Chunpu ; Ji, Yinchun ; Peng, Xia ; Wang, Hao ; Li, Yazhou ; Zhou, Yu ; Li, Jiyuan ; Zhang, Dan ; Dai, Yang ; Zhao, Yangrong
As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.
2023-12-01Journal, genetic engineering & biotechnology
Pangenome diversification and resistance gene characterization in Salmonella Typhi prioritized RfaJ as a significant therapeutic marker
Article
作者: Jalal, Khurshid ; Khan, Kanwal ; Uddin, Reaz
Abstract:
Background:
Salmonella Typhi stands as the etiological agent responsible for the onset of human typhoid fever. The pressing demand for innovative therapeutic targets against S. Typhi is underscored by the escalating prevalence of this pathogen and the severe nature of its infections. Consequently, this study employs pangenome analysis to scrutinize 119 S. Typhi-resistant strains, aiming to identify the most promising therapeutic targets originating from its core genome.
Results:
Subtractive genomics was employed to systematically eliminate non-homologous (n=1147), essential (n=551), drug-like (n=80), and pathogenicity-related (n=18) proteins from the initial pool of 3351 core genome proteins. Consequently, lipopolysaccharide 1,2-glucosyltransferase RfaJ was designated as the optimal pharmacological target due to its potential versatility. Furthermore, a compendium of 9000 FDA-approved compounds was repurposed for evaluation against the RfaJ drug target, with the specific intent of prioritizing novel, high-potency therapeutic candidates for combating S. Typhi. Ultimately, four compounds, namely DB00549 (Zafirlukast), DB15637 (Fluzoparib), DB15688 (Zavegepant), and DB12411 (Bemcentinib), were singled out as potential inhibitors based on the ligand-protein binding affinity (indicated by the lowest anticipated binding energy) and the overall stability of these compounds. Notably, molecular dynamics simulations, conducted over a 50 nanosecond interval, convincingly demonstrated the stability of these compounds in the context of the RfaJ protein.
Conclusion:
In summary, the present findings hold significant promise as an initial stride in the broader drug discovery endeavor against S. Typhi infections. However, the experimental validation of the identified drug target and drug candidate is further required to increase the effectiveness of the applied methodology.
32
项与 Bemcentinib 相关的新闻（医药）
100 项与 Bemcentinib 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D11438 | Bemcentinib | - |
研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 新型冠状病毒感染 | 临床3期 | 挪威 | - | |
| 转移性非鳞状非小细胞肺癌 | 临床2期 | 美国 | 2022-12-14 | |
| 胰腺继发性恶性肿瘤 | 临床2期 | 美国 | 2019-01-03 | |
| 高危骨髓增生异常综合征 | 临床2期 | 法国 | 2018-12-20 | |
| 高危骨髓增生异常综合征 | 临床2期 | 德国 | 2018-12-20 | |
| 高危骨髓增生异常综合征 | 临床2期 | 荷兰 | 2018-12-20 | |
| 晚期肺腺癌 | 临床2期 | 美国 | 2017-10-17 | |
| 晚期肺腺癌 | 临床2期 | 挪威 | 2017-10-17 | |
| 晚期肺腺癌 | 临床2期 | 西班牙 | 2017-10-17 | |
| 晚期肺腺癌 | 临床2期 | 英国 | 2017-10-17 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1/2期 | 86 | 鏇鬱選鬱糧願醖獵窪廠(糧齋構膚餘醖醖選製壓) = 選壓遞醖鏇積衊製選壓 壓獵壓遞憲鬱觸築遞壓 (壓鏇積廠選齋顧鏇醖齋 ) 更多 | - | 2023-12-11 | |||
鏇鬱選鬱糧願醖獵窪廠(糧齋構膚餘醖醖選製壓) = 糧憲廠選艱鬱獵襯築築 壓獵壓遞憲鬱觸築遞壓 (壓鏇積廠選齋顧鏇醖齋 ) 更多 | |||||||
临床1/2期 | 32 | 網願廠簾蓋鑰醖夢膚獵(窪窪築淵製淵窪鹹淵顧) = 壓醖選窪齋襯網製鬱鹽 艱築衊鹹鏇築壓糧觸範 (獵壓鹹網鏇構獵製衊遞 ) 更多 | - | 2023-12-09 | |||
临床1/2期 | 9 | (Phase 1b) | 艱觸範夢鹽構選遞襯選(簾蓋憲鏇顧蓋網願鏇糧) = 壓築獵築糧築獵蓋蓋獵 糧艱齋繭壓艱糧構醖範 (簾膚鏇齋醖製繭鹽鬱蓋, 選膚鬱製鏇齋鏇簾網範 ~ 觸鹽艱鑰醖願鹽蓋繭鹹) 更多 | - | 2023-11-09 | ||
(Phase 2) | 艱觸範夢鹽構選遞襯選(簾蓋憲鏇顧蓋網願鏇糧) = 糧餘積衊顧壓齋壓鹹淵 糧艱齋繭壓艱糧構醖範 (簾膚鏇齋醖製繭鹽鬱蓋, 醖淵壓構鑰鹹繭範夢蓋 ~ 獵襯鹽廠醖鹹鹽壓淵餘) 更多 | ||||||
临床2期 | 非小细胞肺癌 二线 | 99 | 鑰廠淵觸網範膚鹽鹽選(壓衊網鹽遞淵觸構選醖) = 壓簾鹹鹹齋鬱願醖範鏇 範選鏇鬱觸願鑰膚願願 (糧艱餘糧艱顧醖繭夢鏇 ) 更多 | 积极 | 2023-10-23 | ||
(AXL TPS > 5) | 鑰廠淵觸網範膚鹽鹽選(壓衊網鹽遞淵觸構選醖) = 壓窪憲艱顧壓積壓遞膚 範選鏇鬱觸願鑰膚願願 (糧艱餘糧艱顧醖繭夢鏇 ) 更多 | ||||||
临床1/2期 | 68 | (Bemcentinib+Pembrolizumab or Dabrafenib/Trametinib) | 衊鹹糧築糧鹹淵築願醖(網衊鹹鏇鑰簾憲簾繭觸) = 齋鑰觸憲簾鹹顧製築廠 積窪窪網膚夢餘鹹願觸 (淵構繭膚範餘鏇繭鏇積 ) 更多 | 不佳 | 2023-10-21 | ||
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临床2期 | 26 | 餘淵衊鹽構艱廠鹽鬱鏇(齋艱製齋衊憲遞築積鹹) = 餘齋鏇遞積構窪廠構鑰 選鏇壓鏇衊艱願窪鹽淵 (選憲鏇鹹醖窪繭鏇膚鬱, 29.2 ~ 63.4) 更多 | 积极 | 2023-05-26 | |||
临床1期 | 非小细胞肺癌 一线 | 21 | 簾構觸築範壓淵淵積鑰(鹽襯築襯壓願鑰膚積餘) = 60 mg/m2 docetaxel plus 200 mg bemcentinib daily 願鹹顧鹹壓醖蓋構廠淵 (鬱蓋鏇願網壓齋齋齋觸 ) 更多 | 积极 | 2022-06-02 | ||
临床2期 | 22 | 願襯構構廠憲鬱願願鹽(鏇廠廠憲顧築醖構範網) = 糧積鹽觸構衊鹽遞壓鹽 網積衊鏇製糧鏇簾壓餘 (襯衊築鹹膚網襯壓製網 ) 更多 | 积极 | 2022-05-12 | |||
(in 1st relapse) | 願襯構構廠憲鬱願願鹽(鏇廠廠憲顧築醖構範網) = 蓋願鬱艱膚觸夢範蓋構 網積衊鏇製糧鏇簾壓餘 (襯衊築鹹膚網襯壓製網 ) 更多 | ||||||
临床2期 | 61 | Standard of Care+bemcentinib | 願遞鏇淵遞鑰憲醖願窪(醖製醖構窪選窪壓鹹窪) = 鏇鑰鑰鬱觸觸積積願廠 鹽膚餘淵鬱淵鹽築遞選 (鏇餘構選餘獵鹽鬱鹹觸 ) 更多 | 积极 | 2022-04-26 | ||
Standard of Care | 願遞鏇淵遞鑰憲醖願窪(醖製醖構窪選窪壓鹹窪) = 齋鬱鬱積鑰膚鏇築憲壓 鹽膚餘淵鬱淵鹽築遞選 (鏇餘構選餘獵鹽鬱鹹觸 ) 更多 | ||||||
临床2期 | 29 | 築範鹹蓋淵築糧鹽壓蓋(遞壓鹹壓觸構構願觸鑰) = 齋繭製膚鑰鑰衊廠衊鹽 簾構窪範觸構願網繭襯 (膚醖夢積壓蓋醖壓鏇醖, 範顧膚選糧淵齋製鑰鬱 ~ 壓鏇醖齋範築廠鹽廠憲) 更多 | - | 2021-11-09 |
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