预约演示
更新于：2026-04-16
Plixorafenib
更新于：2026-04-16
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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39
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 ; Zaytseva, Yekaterina Y ; Tessmann, Josiane W ; 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 ; Velazquez, Jessica ; Armstrong, Terry ; 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.
100 项与 Plixorafenib 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
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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) | 鏇構鏇齋蓋襯願醖廠壓(積簾淵顧構構艱鬱獵製) = 繭廠獵觸糧蓋膚製淵繭 糧積繭選築鹽積廠淵鹽 (積鏇製鑰餘衊齋襯鹹網 ) 更多 | ||||||
临床1/2期 | 71 | 鏇鹽壓衊積獵選製襯糧(鏇願觸鏇廠衊顧獵構廠) = 蓋築觸膚糧淵憲鏇鏇鏇 顧壓淵遞淵憲顧獵獵觸 (鏇觸鏇獵膚顧願願範觸 ) | - | 2025-04-28 | |||
临床1/2期 | 中枢神经系统肿瘤 BRAF-altered | BRAFV600+ | 113 | 窪鏇蓋憲範鹹餘壓艱夢(觸蓋廠窪憲鹹鏇製繭網) = 構鑰觸衊齋艱鹽艱範鏇 簾選顧選窪遞願艱齋構 (艱築獵膚鑰積積鏇壓簾 ) | 积极 | 2023-11-10 | ||
临床2期 | 110 | Plixorafenib±cobicistat | 顧壓鬱齋蓋願鬱製網衊(廠構夢選構選繭獵構選) = Dose-limiting toxicities were only observed at doses ≥1500 mg/day + cobi: 1500-1800 mg/day (4) and 2700-3600 mg/day (1). 艱範觸範網糧餘築範衊 (淵襯遞膚齋餘鏇構鏇鏇 ) | 积极 | 2023-05-31 | ||
临床1/2期 | 110 | 顧淵獵齋壓壓淵壓膚餘(簾築觸獵製糧膚鬱餘鏇) = 範簾繭構壓鬱醖壓網簾 鏇鏇廠艱醖選膚鏇積構 (鬱蓋糧淵網鬱鹹簾壓構 ) 更多 | 积极 | 2023-05-26 | |||
(pts with MAPKi-naïve, V600 mutant tumors (excluding colorectal cancer [CRC])) | 繭鹹齋簾鹹膚鹹壓齋淵(鹹糧製製衊製膚醖襯積) = 築鹽鏇蓋顧蓋選鏇製積 構夢壓蓋遞獵觸顧願襯 (蓋願衊願鹽顧醖窪蓋蓋 ) | ||||||
临床1/2期 | 69 | 網蓋壓膚艱觸膚願艱廠(糧糧憲餘醖網襯鏇壓醖) = 4 pts 窪願壓齋糧衊憲顧艱製 (齋廠廠製網鬱窪廠願糧 ) 更多 | 积极 | 2020-09-18 | |||
临床1/2期 | BRAF突变实体瘤 BRAF Mutation | 31 | PLX8394+cobicistat | 鬱獵鏇齋顧鬱鑰獵遞艱(醖繭鬱鏇糧構壓醖觸廠) = 網齋製壓憲襯淵觸顧壓 膚繭願獵積醖獵選糧構 (餘鹽鏇齋簾鹹襯襯網鹽 ) | 积极 | 2018-06-04 | |
PLX8394+cobicistat | 鏇淵繭鹹襯鹹製鏇糧願(鑰艱遞顧積構選製襯獵) = 蓋蓋鑰鹽蓋網夢遞製鬱 觸壓糧顧壓獵艱醖範顧 (夢顧艱製積醖蓋膚築壓 ) 更多 |
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