bemcentinib (BGB324) / BerGenBio, Rigel Pharmaceuticals - LARVOL DELTA

GPU-Accelerated Virtual Screening and Molecular Dynamics Simulations for Identification of Novel DPP‑4 Inhibitors. (PubMed, ACS Omega) - "Compounds EPZ005687, OSU-03012, and bemcentinib showed higher binding affinity and more favorable interactions within pockets S1, S2, S1', S2', and S2 ' than the FDA-approved reference drugs like alogliptin, based on MM-GBSA calculations. This combined evidence of high target affinity and enhanced cellular permeability strongly suggests these compounds are up-and-coming antidiabetic agents. These findings demonstrate the efficacy of this integrated computational strategy, along with the utilization of rigorously filtered public databases, for accelerating the discovery of safer and more effective antidiabetic treatments."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Bemcentinib and pembrolizumab in patients with relapsed mesothelioma: MIST3, a phase IIa trial with cellular and molecular correlates of efficacy. (ASCO 2023) - P2 | "MiST3 met its primary endpoint and warrants further evaluation. Analysis of the cellular and molecular correlates of response are ongoing and will be presented. Clinical trial information: NCT03654833."

Clinical • P2a data • Fatigue • Hematological Disorders • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Sarcoma • Solid Tumor

Phase 1 trial of bemcentinib (BGB324), a first-in-class, selective AXL inhibitor, with docetaxel in patients with previously treated advanced non-small cell lung cancer. (PubMed, Lung Cancer) - "Bemcentinib plus docetaxel with G-CSF support demonstrates anti-tumor activity in previously treated, advanced NSCLC. The role of AXL inhibition in the treatment of NSCLC remains under investigation."

Journal • Metastases • P1 data • Fatigue • Febrile Neutropenia • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Respiratory syncytial virus-mediated Gas6/Axl axis induces hyporesponsive macrophages to promote pneumococcal proliferation in the nasopharynx. (PubMed, J Infect Dis) - "Our findings reveal that the RSV infection-induced Gas6/Axl axis facilitates pneumococcal overgrowth by modulating macrophage function. Targeting the RSV-induced Gas6/Axl axis or modulating macrophage polarization may offer novel therapeutic strategies for preventing or managing severe pneumococcal infections exacerbated by viral pathogens such as RSV."

Journal • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • AXL • GAS6

AXL inhibition as an immune-enabling targeted therapy for glioblastoma (SNO 2025) - "In an expanded analysis, comparison across four GSC lines treated with a panel of AXL inhibitors including BMS777607, bemcentinib, ONO-7475, and UNC2025 revealed differential effects on cell viability and proliferation. In conclusion, AXL inhibitors alter gene expression in a similar fashion to EGFR and BRAF inhibitors, differentially kill GSCs, reduce cell proliferation, and differentially alter macrophage immunophenotypes. This work suggests that the choice of AXL inhibitor is critically important when considering effects on the tumor immune milieu and on GBM growth suppression."

Brain Cancer • Glioblastoma • Solid Tumor • EGFR

CD146+ pericyte-like lung cancer brain metastatic stem cells promote tumor angiogenesis through dual regulatory effects on the VEGF/VEGFR axis. (PubMed, Theranostics) - "However, bevacizumab (Bev) shows limited therapeutic effects on NSCLC BrM...Targeting CD146 by imaprelimab or AXL by bemcentinib exhibits more effective anti-angiogenic effects than Bev for BrM in vivo. These findings provide novel anti-vascular strategies for BrM. CD146+ BrM-CSCs promotes high vascularization of lung cancer brain metastases through dual enhancement of VEGF/VEFGR, which suggests that targeting CD146 is a novel anti-vascular strategy for BrM."

Journal • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • GAS6 • KDR • MCAM

Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension. (PubMed, Adv Sci (Weinh)) - "Inhibiting PI3K or administering R428 mitigated AXL-driven RV remodeling in PH, and R428 also ameliorated remodeling in PAB mice. In conclusion, AXL signals the PI3K-AKT pathway to license nuclear translocation of NFIC, thereby dictating the transcription of fibrotic genes in FBs and driving RV remodeling. These findings reveal novel insights into RV pathophysiology and highlight AXL as a potential therapeutic target for PH-induced RV remodeling."

Journal • Cardiovascular • Fibrosis • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • AXL • COL1A1 • NFIC

AXL inhibition as an immune-enabling targeted therapy for glioblastoma (WFNOS 2025) - "In an expanded analysis, comparison across four GSC lines treated with a panel of AXL inhibitors including BMS777607, bemcentinib, ONO-7475, and UNC2025 revealed differential effects on cell viability and proliferation. In conclusion, AXL inhibitors alter gene expression in a similar fashion to EGFR and BRAF inhibitors, differentially kill GSCs, reduce cell proliferation, and differentially alter macrophage immunophenotypes. This work suggests that the choice of AXL inhibitor is critically important when considering effects on the tumor immune milieu and on GBM growth suppression."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • EGFR

Phase Ib/II Study (NCT02488408 / BGBC003) of Bemcentinib Monotherapy or in Combination with Cytarabine or Decitabine in Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS): FINAL Results (ASH 2023) - P1/2 | "However, beyond 1st line (1L), pts have limited treatment options and dismal mOS of 2.3 months (4.7 months in pre-venetoclax era), highlighting the need for more effective treatments in 2nd line (2L) and beyond. BEM demonstrated on-target effect by inhibition of pAXL and downstream signalling in a concentration-dependant manner. BEM monotherapy and in combination was well tolerated across all cohorts. The overall efficacy observed is comparable with historical data in 2L AML and MDS."

Clinical • Combination therapy • Monotherapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

AML Treatment By the AXL Inhibitor Bemcentinib in Combination with Cytarabine Shows Clinical Efficacy Related to TNFα and Cytotoxic Immune Cells: A Single-Cell Translational Study from the BGBC003 Trial (ASH 2023) - P1/2 | "Such patients benefit from hypomethylating agents and venetoclax but frequently develop resistance to this treatment regimen. Additionally, extended research on TNFα and cytotoxic immune cells may lead to a better understanding of what mechanisms cause a treatment response. This may ultimately enable an accurate selection of patients who will benefit from bemcentinib-LDAC."

Clinical • Combination therapy • Immune cell • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD8 • IFNA1 • IFNG • TNFA

AXL Disrupts the Integrity of the Slit Diaphragm by Inhibiting ZO-1 Phase Separation and Aggravates Podocyte Injury in Diabetic Nephropathy (KIDNEY WEEK 2025) - "In db/db diabetic mice in vivo, overexpression of AXL worsened podocyte injury, whereas AXL inhibitor R428 significantly alleviated this effect...Conclusion Our results suggest that AXL disrupts the integrity of the slit diaphragm by inhibiting the ZO-1 phase separation, causing the loosening of tight junctions, thereby disrupting the SD integrity and exacerbating podocyte injury and proteinuria. AXL may serve as a potentially new target for podocyte-specific therapeutics in regulating the slit diaphragm, providing a novel direction for the treatment of diabetic nephropathy."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease • AXL • TJP1

Prior therapy modulates the influence of Axl inhibition on myeloid cell state in a human in vitro tumor microenvironment (SITC 2025) - "Axl is a receptor tyrosine kinase that has gained attention as a therapeutic target, as its inhibition is hypothesized to promote tumor cell death and myeloid cell activation – both prerequisites to T cell infiltration.3–5 However, Axl inhibition has had mixed clinical results,6–8 necessitating a deeper understanding of the mechanistic effects of Axl inhibition on myeloid cell activation in the tumor microenvironment.Methods We generated injured and untreated A375 human malignant melanoma populations by treating cells with trametinib + dabrafenib or DMSO, respectively, for 24 hours followed by 24 hours of rest. We then co-cultured each A375 population with macrophages for 24 hours with or without the Axl-specific small molecule inhibitor bemcentinib...Red ellipses indicate macrophage clusters of interest. n = 4 independent donors"

IO biomarker • Preclinical • Tumor microenvironment • Melanoma • Oncology • Solid Tumor

Evaluation of TAM Receptor Targeting in Pathophysiology of Idiopathic Pulmonary Fibrosis. (PubMed, Medicina (Kaunas)) - "Materials and IPF fibroblasts (IPF FBs) and control human pulmonary fibroblasts (HPFs) were treated with R428 (Axl-specific inhibitor), LDC1267 (TAM inhibitor), or Nintedanib (an IPF-approved drug) to evaluate the influence of these drugs on cell proliferation, migration, and the expression of pro-inflammatory and pro-fibrotic genes. These findings suggest that R428 and LDC1267 modulate the proliferation, migration, and gene expression of activated fibroblasts via TAM signaling. Fibroblast-mediated effects on macrophage polarization underscore the relevance of intercellular crosstalk in fibrotic disease."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • ACTA2 • AXL • COL1A1 • CXCL10 • FN1 • GAS6 • MRC1 • TGFB1 • TNFA

TAM family kinases are potential candidate targets for therapeutic intervention in chronic myeloid leukemia. (PubMed, Discov Oncol) - "TAM family kinase inhibitors significantly reduce the proliferation and colony formation of K562-S and K562-R cells by inducing apoptosis, interfering with Wnt/β catenin pathway, and upregulating cell cycle inhibitors."

Journal • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABL1 • AXL • CDKN1A • MERTK • MYC

Targeted Therapies Modulating Mesenchymal-Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib. (PubMed, J Clin Med) - "Although these targeted therapies show potential to overcome resistance and improve patient outcomes, challenges remain due to the complex regulation of EMP. Future directions focus on refining combination strategies and advancing personalized approaches to enhance efficacy across multiple cancer types."

Biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • GAS6 • MET • TGFB1

KNOWLEDGE DISCOVERY IN DATASETS: DRUGGABLE TARGETS FOR PANCREATIC DUCTAL ADENOCARCINOMA (UEGW 2025) - "Of note, EIF2A had high affinity to Padnarsertib (orally small molecular drug) with -11.4 kcal/mol, whereas STAMBP had affinity to Bemcentinib (orally small molecular drugs) with -11.8 kcal/mol, and ANXA2 and AHNAK2 to Zavegepant (CGRP receptor antagonist as migraine drug) with -12.1 kcal/mol and -11.4 kcal/mol, respectively, suggesting druggable targets on endocytosis/exocytosis/phagocytosis and CGRP signaling pathways. Potential druggable targets for PDAC were identified by KDD, particularly including the key proteins with repurposed drugs acting on the ERK/MAPK signaling pathway (involved CGRP) and the membrane fusion."

CNS Disorders • Migraine • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ACADSB • AHNAK2 • ANXA2 • ANXA3 • EIF2A • EIF2S1 • MYH14 • POLR2H • SPTAN1 • VIL1

Inhibition of the Caveolin-1 pathway promotes apoptosis and overcomes pan-tyrosine kinase inhibitor resistance in hepatocellular carcinoma. (PubMed, Cell Death Dis) - "Combination therapy using either lenvatinib or sorafenib and selective CAV1 inhibitors (e.g., siCAV1/miR-7), or AXL/FGFR4 inhibitors (e.g., BGB324/BLU9931) effectively overcame pan-TKI resistance. Our findings highlight a previously unrecognized role for CAV1-driven signalling in sustaining tumour dormancy, a critical and challenging therapeutic barrier underlying recurrence and pan-TKI resistance in HCC. Therapeutically targeting these pathways offer a promising and novel strategy to eliminate dormant tumour cells, thereby overcoming resistance and improving treatment outcomes."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CAV1 • CDH1 • CDKN1A • FGFR4 • MIR7 • RAC1

Reversing Preeclampsia Pathology: AXL Inhibition Restores Mitochondrial Function and ECM Balance. (PubMed, Cells) - "Pregnant rats were administered Gas6 to induce PE-like symptoms such as hypertension and proteinuria; a subset also received the AXL inhibitor R428...AXL inhibition activated compensatory pathways beyond Gas6 blockade, unveiling novel mechanisms for PE resolution. These findings position AXL inhibitors as promising therapeutics, offering insights into mitochondrial and fibrotic targets to mitigate this enigmatic disorder."

Journal • Cardiovascular • Fibrosis • Gynecology • Hypertension • Immunology • Inflammation • Renal Disease • COL4A1 • COX5A • GAS6 • LAMC1

AXL: an emerging biomarker and putative tyrosine kinase inhibitor target (ECP 2025) - "Several AXL inhibitors, including BGB324 and R428, are currently undergoing clinical trials to evaluate their efficacy in overcoming TKI resistance or as potential novel stand-alone therapies across various malignancies... Our primary findings highlight the importance of closely examining the molecular mechanisms underlying AXL signalling and AXL-mediated therapy resistance."

Biomarker • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • AXL

Phytochemicals as potential AXL inhibitors for cancer therapy: A computational study. (PubMed, Comput Biol Chem) - "Furthermore, molecular dynamics simulation over 200 ns revealed stable protein-ligand complexes with some minor conformational fluctuations. This study suggests that, after further experimentation, modulating AXL with natural compounds holds promise for combating human malignancies, potentially overcoming limitations of existing synthetic inhibitors such as R428."

Journal • Melanoma • Oncology • Pain • Pancreatic Cancer • Solid Tumor • GAS6

Substituted Triazole-3,5-Diamine Compounds as Novel Human Topoisomerase III Beta Inhibitors. (PubMed, Int J Mol Sci) - "Five compounds with comparable IC50 to that of bemcentinib for the inhibition of hTOP3B were identified. These results suggest that the exploration of tyrosine kinase inhibitors and their analogs may allow the identification of novel potential topoisomerase inhibitors."

Journal • Dengue Fever • AXL

The Role of Axl Inhibition and Immune Checkpoint Blockade in Non-small Cell Lung Cancer: Current Understanding and Treatment Strategies. (PubMed, Cancer Diagn Progn) - "Preclinical studies highlight the efficacy of Axl inhibitors, such as bemcentinib, brigatinib, and enapotamab vedotin, in overcoming drug resistance and enhancing immune responses. Clinical trials combining Axl inhibitors with ICIs (e.g., pembrolizumab) show promise, particularly in STK11-mutant NSCLC, with manageable toxicity profiles. However, challenges persist in optimizing dosing, managing adverse events, and identifying predictive biomarkers. Ongoing research into combination strategies and biomarker-driven approaches aims to refine Axl-targeted therapies and improve outcomes for patients with advanced NSCLC."

Checkpoint inhibition • IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • STK11

Inhibition of Axl attenuates acute kidney injury by alleviating inflammation via SOCS3 downregulation in tubular epithelial cells. (PubMed, BMC Nephrol) - "The Axl-SOCS3 axis exacerbates AKI by reinforcing NF-κB-driven inflammation in TECs, creating a vicious cycle between immune cells and TECs. Targeting this cross-cellular pro-inflammatory pathway offers a promising therapeutic strategy for AKI."

Journal • Acute Kidney Injury • Cardiovascular • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • IL1B • IL6 • SOCS3

Alveolar macrophages control fibroblast into CAF fate in Non-Small Cell Lung Cancer (NSCLC) (EACR 2025) - "Finally, as AM-depleted tumors are significantly infiltrated with CD4 and CD8 T cells resulting in a longer survival, we plan to interrogate the impact of early AXL inhibition (Bemcentinib) in KP-tumors to boost T cell surveillance in otherwise T cell dessert tumors. Altogether, our work highlights a novel regulatory axis between AM and CAF that can be therapeutically exploited to promote immune T cell surveillance in NSCLC. We identified AMs as drivers of pathological responses in CAFs via AXL activation."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ACTA2 • CAFs • CD8 • PDGFRA • PROS1 • PTPRC • TGFB1

AXL enhances the self-renewal of cancer stem-like cells and Osimertinib chemoresistance by regulating SCD1 in non-small cell lung cancer. (PubMed, Biochem Pharmacol) - "Moreover, targeting AXL with R428 significantly suppressed the self-renewal ability of CSCs and increased their sensitivity to Osimertinib. Taken these together, our study provides new insight into the role and mechanism of AXL in regulating NSCLC CSCs stemness. Our study also gives a new hint for the relationship between AXL and SCD1."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • SCD • SREBF1