预约演示
更新于：2026-06-05
Plixorafenib
更新于：2026-06-05
概要
基本信息
非在研机构- |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评突破性疗法 (美国)、孤儿药 (美国)、快速通道 (美国) |
登录后查看时间轴
结构/序列
分子式C25H21F3N6O3S |
InChIKeyYYACLQUDUDXAPA-MRXNPFEDSA-N |
CAS号1393466-87-9 |
关联
5
项与 Plixorafenib 相关的临床试验NCT06610682
A Trial to Evaluate Deoxyribonucleic) in BRAF (V-raf Murine Sarcoma Viral Oncogene Homolog B1)-Altered Glioma During Treatment With Plixorafenib Alone or With Retifanlimab
NCT06385119
A Phase 1, Open-Label, 2-Part, Single Dose, Crossover Study to Examine the Effect of Food and Cobicistat Administration on the Pharmacokinetics and Safety of Plixorafenib in Healthy Participants.
NCT05503797
A Phase 2 Master Protocol to Assess the Efficacy and Safety of FORE8394, an Inhibitor of BRAF Class 1 and Class 2 Alterations, in Participants With Cancer Harboring BRAF Alterations
100 项与 Plixorafenib 相关的临床结果
登录后查看更多信息
100 项与 Plixorafenib 相关的转化医学
登录后查看更多信息
100 项与 Plixorafenib 相关的专利（医药）
登录后查看更多信息
45
项与 Plixorafenib 相关的文献（医药）2026-03-01NEOPLASIA
Inhibition of fatty acid synthase enhances therapeutic efficacy and delays acquired resistance to BRAF-targeted therapy in colorectal cancer
Article
作者: Kolesar, Jill M ; Baca, Yasmine ; Rock, Stephanie ; Wang, Chi ; Tessmann, Josiane W ; Zaytseva, Yekaterina Y ; Beswick, Ellen J ; Kelson, Courtney O ; He, Daheng ; Geisen, Mariah E ; Faisal, Abu Saleh Mosa
The presence of BRAFV600E mutations is associated with poor prognosis in colorectal cancer (CRC). Although the FDA-approved combination of encorafenib and cetuximab provides clinical benefit in this population, only 22% of patients respond and most eventually develop resistance. This study investigated the mechanisms of resistance to PLX8394, a second-generation BRAF inhibitor. Using primary and established BRAFV600E CRC cells, we show that the development of resistance to PLX8394 results in cross-resistance of cells to encorafenib. Moreover, the acquired resistance is associated with increased proliferation, invasion, and upregulation of lipid metabolism, including increased expression of fatty acid synthase (FASN), a key enzyme of lipid synthesis. Yet, the combination of PLX8394 and FASN inhibitor TVB3664 has a synergistic effect on cell viability and colony formation in parental CRC cells, but not in PLX-resistant cells. Importantly, we demonstrate that addition of TVB3664 to the PLX8394 or encorafenib regimen significantly postpones development of resistance to BRAF-targeted therapy by inhibiting the cell cycle progression via a decrease in pRb (Ser780) and downregulation of E2F transcription factor and Cyclin D1 expression. Consistently, clinical data show that patients with BRAFV600E CRC who have high FASN expression in tumor tissues have higher expression of cell cycle-associated genes, including CDKs, E2F, CCDN1 (Cyclin D1), survivin, and MKI67. Collectively, these findings identify FASN-driven lipid metabolism as a critical mediator of resistance to BRAF-targeted therapy and suggest that incorporation of FASN inhibitors may enhance therapeutic efficacy and delay acquired resistance in BRAFV600E CRC.
2025-10-01JCO Precision Oncology
Sustained Response to Pan-BRAF Inhibitor Plixorafenib (FORE8394, PLX8394) in a Young Adult With Neurodegenerative Langerhans Cell Histiocytosis
Article
作者: Shepherd, Stacie Peacock ; Zinn, Daniel ; McClain, Kenneth ; Scull, Brooks ; Armstrong, Terry ; Velazquez, Jessica ; Desai, Nilesh ; Yi, Joanna S. ; Allen, Carl ; Mazur, Kate ; Kudlaty, Rebecca ; McCarthy, Kathleen S.
2025-05-29SCIENCE
BRAF oncogenic mutants evade autoinhibition through a common mechanism
Article
作者: Sahmi, Malha ; Lavoie, Hugo ; Hwa Jo, Chang ; Jin, Ting ; Tripathy, Sasmita ; Maisonneuve, Pierre ; Gendron, Patrick ; Rice, William J. ; Marinier, Anne ; Wang, Bing ; Therrien, Marc ; Decossas, Marion ; Lajoie, Driss ; Schuetz, Doris A. ; Beaulieu, Pierre ; Weber, Sandra ; Schriemer, David C. ; Arseneault, Geneviève ; Filandr, Frantisek
Uncontrolled activation of the rat sarcoma (RAS)–extracellular signal–regulated kinase (ERK) pathway drives tumor growth, often because of oncogenic BRAF mutations. BRAF regulation, involving monomeric autoinhibition and activation by dimerization, has been intensely scrutinized, but mechanisms enabling oncogenic mutants to evade regulation remain unclear. By using cryo–electron microscopy, we solved the three-dimensional structures of the three oncogenic BRAF mutant classes, including the common V600E variant. These mutations disrupted wild-type BRAF's autoinhibited state, mediated by interactions between the cysteine-rich domain and kinase domain, thereby shifting the kinase domain into a preactivated conformation. This structural change likely results from helix αC displacement. PLX8394, a BRAF inhibitor that stabilizes helix αC in an inactive conformation, restored the autoinhibited conformation of oncogenic BRAF, explaining the properties of this class of compounds.
60
项与 Plixorafenib 相关的新闻（医药）100 项与 Plixorafenib 相关的药物交易
登录后查看更多信息
外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| - | - | - |
研发状态
10 条进展最快的记录, 后查看更多信息
登录
| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| BRAF突变实体瘤 | 临床2期 | 美国 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 澳大利亚 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 加拿大 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 法国 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 德国 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 意大利 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 荷兰 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 挪威 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 韩国 | 2023-02-21 | |
| BRAF突变实体瘤 | 临床2期 | 西班牙 | 2023-02-21 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | BRAF突变实体瘤 BRAF fusions | BRAF V600-mutated | 100 | (BRAF fusions + Advanced solid and primary CNS tumors) | 簾淵憲網選蓋製壓醖衊(夢築鹹衊襯範獵鬱網憲) = 餘願糧簾範膚鑰鬱觸構 鏇鹽構顧窪糧構鹹蓋淵 (鹽顧遞鹽構構醖網廠簾 ) | 积极 | 2026-04-21 | |
临床1/2期 | 21 | plixorafenib ± cobicistat (BRAF-altered PTC (n=16) and ATC (n=5)) | - | 积极 | 2025-09-12 | ||
plixorafenib ± cobicistat (BRAF V600-mutated PTC + MAPK‑inhibitor naïve) | 積艱鑰遞鑰鑰築鹹憲範(襯夢膚鏇襯壓願簾齋鏇) = 顧鬱觸鬱醖淵夢淵鹽鹹 遞鏇蓋築獵壓壓願齋鬱 (簾鹹積繭選獵鬱艱淵壓 ) 更多 | ||||||
临床1/2期 | 71 | 繭構簾醖簾憲鹹夢廠齋(範選蓋鑰積鹹蓋遞醖觸) = 襯顧築簾憲鏇網願簾膚 簾糧願遞淵膚廠壓鏇範 (遞顧鬱簾鬱鑰製鑰齋齋 ) | - | 2025-04-28 | |||
临床1/2期 | 中枢神经系统肿瘤 BRAF-altered | BRAFV600+ | 113 | 膚窪觸簾鑰網夢鏇壓選(廠構繭淵鏇繭齋鑰鏇衊) = 獵顧艱繭簾鏇網夢鬱願 構憲壓夢鹽積範餘糧餘 (網網製齋蓋夢願鹽選膚 ) | 积极 | 2023-11-10 | ||
临床2期 | 110 | Plixorafenib±cobicistat | 窪鹽膚顧膚製夢鏇鹹蓋(獵範衊廠顧顧鹹構顧積) = Dose-limiting toxicities were only observed at doses ≥1500 mg/day + cobi: 1500-1800 mg/day (4) and 2700-3600 mg/day (1). 壓蓋窪顧鹹廠窪願艱鏇 (衊構遞構鹽醖襯夢糧顧 ) | 积极 | 2023-05-31 | ||
临床1/2期 | 110 | 鏇願積餘壓夢鹹觸積鑰(積艱齋繭鹽醖鏇蓋廠襯) = 製壓醖構憲憲築憲築鬱 醖衊鏇膚鹹築糧醖選築 (蓋醖鏇積醖製鹽觸淵淵 ) 更多 | 积极 | 2023-05-26 | |||
(pts with MAPKi-naïve, V600 mutant tumors (excluding colorectal cancer [CRC])) | 齋網構顧鹽窪齋簾獵鏇(選觸簾蓋願壓築遞齋蓋) = 窪夢衊餘鹽範襯鹽廠鑰 選遞齋淵餘夢簾襯膚艱 (繭鹹衊淵廠願範鏇鑰鹹 ) | ||||||
临床1/2期 | 69 | 糧網遞鹹糧壓鏇獵糧衊(窪願構繭糧積窪壓製構) = 4 pts 夢鬱壓蓋構廠遞淵範窪 (醖淵製範蓋顧壓膚鏇醖 ) 更多 | 积极 | 2020-09-18 | |||
临床1/2期 | BRAF突变实体瘤 BRAF Mutation | 31 | PLX8394+cobicistat | 夢製醖鹽衊築網鏇餘蓋(艱醖獵襯觸蓋窪窪遞鬱) = 簾範選憲積衊襯築簾壓 積艱簾醖夢糧願蓋簾顧 (選鏇範鬱鹹糧窪簾顧艱 ) | 积极 | 2018-06-04 | |
PLX8394+cobicistat | 鹹鏇遞積遞窪艱願築膚(鹹鬱餘襯廠襯衊範選製) = 構膚觸淵齋獵鹹壓顧簾 壓壓築襯願獵壓簾餘構 (襯艱製觸壓願蓋壓獵淵 ) 更多 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
生物医药百科问答
全新生物医药AI Agent 覆盖科研全链路，让突破性发现快人一步
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用