^
    6ms
    BRAF oncogenic mutants evade autoinhibition through a common mechanism. (PubMed, Science)
    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.
    Journal
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF mutation • BRAF V600 • BRAF wild-type
    |
    plixorafenib (FORE-8394)
    8ms
    A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations (clinicaltrials.gov)
    P2, N=250, Recruiting, Fore Biotherapeutics | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)
    8ms
    Feasibility of CSF and Plasma ctDNA in BRAF-altered Glioma During Treatment With Plixorafenib (clinicaltrials.gov)
    P1, N=15, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting
    Enrollment open • Circulating tumor DNA
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)
    9ms
    A Study of the Effects of Food and Cobicistat on Plixorafenib Pharmacokinetics in Healthy Volunteers. (clinicaltrials.gov)
    P1, N=28, Completed, Fore Biotherapeutics | Recruiting --> Completed
    Trial completion
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)
    9ms
    Feasibility of CSF and Plasma ctDNA in BRAF-altered Glioma During Treatment With Plixorafenib (clinicaltrials.gov)
    P1, N=15, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Recruiting | Trial completion date: May 2027 --> May 2026 | Trial primary completion date: Dec 2026 --> Dec 2025
    Enrollment open • Trial completion date • Trial primary completion date • Circulating tumor DNA
    |
    BRAF (B-raf proto-oncogene)
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)
    10ms
    Oncogenic non-V600 mutations evade the regulatory machinery of RAF including the Cdc37/Hsp90 chaperone and the 14-3-3 scaffold. (PubMed, Theranostics)
    These BRAF mutants with high dimer propensity sustained a prolonged ERK signaling, and were effectively targeted by RAF dimer breaker plx8394 in vitro and in vivo... Cdc37/Hsp90 chaperones and 14-3-3 scaffolds cooperatively facilitate the switch of RAF proteins from open active dimers to close inactive monomers. Non-V600 mutations disrupt this regulatory machinery, and trap RAF in dimers, which could be targeted by RAF dimer breakers.
    Journal
    |
    BRAF (B-raf proto-oncogene) • ARAF (A-Raf Proto-Oncogene) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    BRAF V600E
    |
    plixorafenib (FORE-8394)
    11ms
    Feasibility of CSF and Plasma ctDNA in BRAF-altered Glioma During Treatment With Plixorafenib (clinicaltrials.gov)
    P1, N=15, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRAF (B-raf proto-oncogene)
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)
    12ms
    A Study of the Effects of Food and Cobicistat on Plixorafenib Pharmacokinetics in Healthy Volunteers. (clinicaltrials.gov)
    P1, N=28, Recruiting, Fore Biotherapeutics | N=12 --> 28
    Enrollment change
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)
    1year
    Feasibility of CSF and Plasma ctDNA in BRAF-altered Glioma During Treatment With Plixorafenib (clinicaltrials.gov)
    P1, N=15, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    New P1 trial
    |
    BRAF (B-raf proto-oncogene)
    |
    plixorafenib (FORE-8394)
    1year
    A Study to Assess the Efficacy and Safety of FORE8394 in Participants with Cancer Harboring BRAF Alterations (clinicaltrials.gov)
    P2, N=250, Recruiting, Fore Biotherapeutics | N=135 --> 250
    Enrollment change
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)
    over1year
    PLX120-03: A Study of FORE8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors (clinicaltrials.gov)
    P1/2, N=113, Completed, Fore Biotherapeutics | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2024
    Trial completion • Trial completion date • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    plixorafenib (FORE-8394)
    over1year
    A Study of the Effects of Food and Cobicistat on Plixorafenib Pharmacokinetics in Healthy Volunteers. (clinicaltrials.gov)
    P1, N=12, Recruiting, Fore Biotherapeutics | Not yet recruiting --> Recruiting
    Enrollment open
    |
    plixorafenib (FORE-8394) • Tybost (cobicistat)