^
    4d
    a Study to Evaluate the Safety and Efficacy of D-1553 Combined With IN10018 in KRAS G12C Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=140, Recruiting, InxMed (Shanghai) Co., Ltd. | Trial completion date: Dec 2026 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Anfangning (garsorasib) • ifebemtinib (IN10018)
    4d
    A Phase 3 Study of IN10018 in Combination With D-1553 Versus Standard Therapy for First Line Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (clinicaltrials.gov)
    P3, N=400, Recruiting, InxMed (Shanghai) Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    cisplatin • carboplatin • Tevimbra (tislelizumab-jsgr) • pemetrexed • Anfangning (garsorasib) • ifebemtinib (IN10018)
    5d
    IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma (clinicaltrials.gov)
    P1, N=51, Completed, InxMed (Shanghai) Co., Ltd. | Active, not recruiting --> Completed | N=120 --> 51
    Trial completion • Enrollment change
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • NRAS Q61 • NRAS G12 • NRAS G13
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib) • ifebemtinib (IN10018)
    7d
    RAMP 203: Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (clinicaltrials.gov)
    P1/2, N=153, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Jun 2026
    Enrollment closed • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Lumakras (sotorasib) • Avmapki (avutometinib) • Fakzynja (defactinib)
    7d
    A071401: Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas (clinicaltrials.gov)
    P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PTCH1 (Patched 1) • CDK4 (Cyclin-dependent kinase 4) • NF2 (Neurofibromin 2) • SMO (Smoothened Frizzled Class Receptor) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)
    |
    PIK3CA mutation • PTEN mutation • AKT1 mutation
    |
    Verzenio (abemaciclib) • Truqap (capivasertib) • Erivedge (vismodegib) • GSK2256098
    8d
    Inactivation of Focal Adhesion Kinase FAK Rapidly Abrogates Keratinocyte Entry in Mitosis via Rho-Associated Kinase, Resulting in Squamous Differentiation. (PubMed, FASEB J)
    To investigate whether FAK plays a role in this checkpoint, we inactivated the protein in normal human oral keratinocytes by specific shRNAs or by the specific inhibitor defactinib...Concomitant inhibition of FAK-downstream Rho-associated kinase (Rock) rescued mitotic progression. The results unveil a rapid Rock-dependent mitosis switch upon inactivation of FAK, inducing terminal differentiation, pointing at a mitotic automatic mechanism of epithelia to suppress suprabasal proliferation of precancerous cells.
    Journal
    |
    TP53 (Tumor protein P53)
    |
    Fakzynja (defactinib)
    13d
    Protective effects of traditional Chinese medicines Aconiti Lateralis Radix Praeparata and Angelicae Sinensis on H/R cardiomyocytes via the PI3K/Akt/GSK-3β pathway and autophagy pathway. (PubMed, Medicine (Baltimore))
    This study demonstrated that the combination of Aconiti Lateralis Radix Praeparata and Angelicae Sinensis significantly protected H/R cardiomyocytes in vitro. This protective effect was achieved through enhancing cell viability, reducing oxidative stress-induced injury, and modulating the expression and distribution of key proteins and genes. The underlying mechanisms involved the activation of the PI3K/Akt/GSK-3β signaling pathway and the autophagy pathway, as confirmed by the inhibitory effect of LY294002.
    Journal
    |
    BCL2 (B-cell CLL/lymphoma 2) • ANXA5 (Annexin A5)
    |
    LY294002
    13d
    Phase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer (clinicaltrials.gov)
    P1, N=31, Not yet recruiting, M.D. Anderson Cancer Center
    New P1 trial
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • RAS mutation • HRAS mutation
    |
    everolimus • Avmapki (avutometinib) • Fakzynja (defactinib)
    15d
    Stereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P2, N=36, Not yet recruiting, Washington University School of Medicine
    New P2 trial
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    19d
    Succinate Promotes M1 Polarization of Intestinal Macrophages in Mice With Necrotizing Enterocolitis Through the PI3K/AKT Pathway. (PubMed, Pediatr Discov)
    Further experiments revealed that the expression of polarization-related markers in M1-type macrophages was significantly suppressed after treatment with the SUCNR1-neutralizing antibody or the PI3K inhibitor LY294002. These findings suggest that succinate may activate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway via SUCNR1 to promote the polarization of NEC macrophages toward the M1 phenotype, thereby accelerating NEC progression.
    Preclinical • Journal
    |
    HIF1A (Hypoxia inducible factor 1, alpha subunit) • ARG1 (Arginase 1) • MRC1 (Mannose Receptor C-Type 1) • CD86 (CD86 Molecule) • SUCNR1 (Succinate Receptor 1)
    |
    LY294002
    20d
    Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma (clinicaltrials.gov)
    P2, N=42, Active, not recruiting, Washington University School of Medicine | Trial primary completion date: Dec 2025 --> Apr 2026
    Trial primary completion date
    |
    Fakzynja (defactinib)
    20d
    DACT1 inhibits cuproptosis and promotes cell malignancy via activation of PI3K/AKT signaling in laryngeal squamous cell carcinoma. (PubMed, Eur J Med Res)
    DACT1 promotes the malignant behavior of LSCC cells and suppresses cuproptosis by activating the PI3K/AKT signaling.
    Journal
    |
    LIAS (Lipoic Acid Synthetase)
    |
    LY294002 • elesclomol (STA-4783)