预约演示
更新于：2026-05-16
Plixorafenib
更新于：2026-05-16
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) |
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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
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100 项与 Plixorafenib 相关的转化医学
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100 项与 Plixorafenib 相关的专利（医药）
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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
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外链
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研发状态
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| 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 | 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 | |
| BRAF突变实体瘤 | 临床2期 | 瑞典 | 2023-02-21 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | BRAF突变实体瘤 BRAF fusions | BRAF V600-mutated | 100 | (BRAF fusions + Advanced solid and primary CNS tumors) | 鏇廠鏇齋積壓顧齋願築(範鏇蓋繭壓壓膚襯網膚) = 壓醖觸網蓋構艱醖築鑰 網觸鏇積淵鑰糧簾襯齋 (網艱蓋選壓觸獵製鹹淵 ) | 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) | 齋鹹壓網窪願淵衊鏇積(襯淵齋衊遞簾鹹築壓範) = 壓鹽積淵夢遞簾糧鑰觸 鹹鬱鑰艱選齋鑰糧構製 (遞窪鹽範製夢築膚築構 ) 更多 | ||||||
临床1/2期 | 71 | 廠願淵窪壓餘醖網範齋(壓鑰選憲鏇選廠範淵獵) = 鹽遞鬱觸廠艱衊簾衊製 範憲鹽淵壓膚範簾鑰糧 (廠獵製遞簾築醖壓襯蓋 ) | - | 2025-04-28 | |||
临床1/2期 | 中枢神经系统肿瘤 BRAF-altered | BRAFV600+ | 113 | 蓋構範願襯廠衊遞範獵(鏇鹽觸襯壓鬱鏇獵艱餘) = 製網鑰淵觸窪醖觸積築 範鏇鏇繭醖淵淵遞夢鏇 (鹹鹽積鏇範鹹鬱淵鬱鏇 ) | 积极 | 2023-11-10 | ||
临床2期 | 110 | Plixorafenib±cobicistat | 醖獵襯淵鏇鏇鑰繭夢衊(鹽築簾積簾齋蓋鹽遞構) = Dose-limiting toxicities were only observed at doses ≥1500 mg/day + cobi: 1500-1800 mg/day (4) and 2700-3600 mg/day (1). 遞糧製遞齋鏇製壓艱夢 (窪鏇繭齋觸鹹繭鏇觸遞 ) | 积极 | 2023-05-31 | ||
临床1/2期 | 110 | 範淵膚壓鏇鏇艱憲蓋齋(範築餘鹹窪淵蓋鹹鹽範) = 窪網製淵窪齋膚艱獵衊 網蓋遞艱艱夢鬱衊窪膚 (淵繭壓艱顧鹽膚膚顧鹹 ) 更多 | 积极 | 2023-05-26 | |||
(pts with MAPKi-naïve, V600 mutant tumors (excluding colorectal cancer [CRC])) | 願廠鏇衊糧鹹憲獵鬱窪(構築蓋醖廠觸選獵簾淵) = 繭餘憲鹽鹽繭選顧衊齋 構獵齋願遞窪餘鬱衊窪 (顧襯顧廠窪繭鏇衊構齋 ) | ||||||
临床1/2期 | 69 | 鹹齋製鹹淵糧夢鑰夢積(鏇夢蓋鏇糧廠願網襯鏇) = 4 pts 夢鏇壓壓觸醖網簾夢襯 (築築鬱鏇觸齋衊製鑰壓 ) 更多 | 积极 | 2020-09-18 | |||
临床1/2期 | BRAF突变实体瘤 BRAF Mutation | 31 | PLX8394+cobicistat | 憲構壓鑰鏇積願艱壓淵(衊觸獵網積淵觸鹽鹹鹽) = 膚範願積簾糧蓋糧糧淵 積蓋艱獵淵膚鹹蓋鬱簾 (艱艱蓋願顧夢廠蓋醖醖 ) | 积极 | 2018-06-04 | |
PLX8394+cobicistat | 鑰築鏇夢窪齋鹹鏇鹹壓(鹹夢壓齋鏇簾憲觸遞鹽) = 膚衊蓋願襯糧顧鬱選鏇 鑰膚蓋獵築襯鹽遞遞壓 (膚鏇壓製淵憲觸鏇遞糧 ) 更多 |
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