bafetinib (INNO-406) / LadRx - LARVOL DELTA

Mesothelin Promotes Acute Myeloid Leukemia Cell Proliferation, Adhesion, and Chemoresistance through Novel Binding Partner Lyn (ASH 2024) - "To investigate the role of Lyn in MSLN-induced resistance to Ara-C, we used saracatinib (pan-SFK inhibitor) and bafetinib (Lyn inhibitor) in conjunction with Ara-C. Taken together, our data support MSLN playing an oncogenic role through increased proliferation, cell cycle progression, metabolic fitness, ECM adhesion, and Ara-C resistance. We identified a novel MSLN-Lyn signaling axis that could be used to improve targeted therapy approaches."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • LYN • MSLN • MUC16

Lyn kinase palmitoylation promotes eosinophil activation and allergic airway inflammation via ST2 signaling. (ERS 2025) - "Inhibition of Lyn activation by Bafetinib, a specific inhibitor of Lyn, could suppress eosinophil activation (G- H) . Conclusions Lyn palmitoylation promotes Lyn kinase activation by facilitating its binding to ST2, then further regulates eosinophil activation and allergic airway inflammation."

Asthma • Inflammation • Respiratory Diseases • IL33 • LYN

Identification of potential Abl kinase inhibitors using virtual screening and free energy calculations for the treatment of chronic myeloid leukemia. (PubMed, Biophys Chem) - "Five candidate compounds emerged with binding energies comparable to or higher than known Abl kinase inhibitors, including Imatinib and Bafetinib. Finally, based on these calculations, we selected two compounds as candidates as Abl tyrosine kinase inhibitors. Overall, the results showed the effectiveness of combining ligand-based and structure-based drug design strategies to identify new Abl kinase inhibitor leads for improved the CML therapy."

Journal • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Differential vascular endothelial cell toxicity of established and novel BCR-ABL tyrosine kinase inhibitors. (PubMed, PLoS One) - "Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib...Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile."

Journal • Cardiovascular • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Respiratory Diseases • Thrombosis • ABL1 • BCR • ICAM1 • VCAM1

Target deconvolution with matrix-augmented pooling strategy reveals cell-specific drug-protein interactions. (PubMed, Cell Chem Biol) - "We further validated BRAF and CSNK2A2 as potential off-targets of bafetinib and abemaciclib, respectively. This work represents the largest thermal profiling of structurally diverse drugs across multiple cell lines to date."

Journal • Developmental Disorders • BRAF

Tyrosine Kinase Inhibitor Profiling Using Multiple Forskolin-Responsive Reporter Cells. (PubMed, Int J Mol Sci) - "Among them, dasatinib and bosutinib, and imatinib and bafetinib showed homologous profiling. The tyrosine kinase inhibitors mentioned above are approved as anticancer agents, and the system could be used for similarity evaluation, efficacy prediction, etc., in the development of new anticancer agents."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study. (PubMed, Int J Mol Sci) - "Among these 27 compounds, the drugs Bafetinib, Radotinib, Flumatinib, and Imatinib showed higher affinity for this tyrosine kinase receptor, lying in the nanomolar order, while the natural products included in this group, such as curcumin, luteolin, and epigallocatechin gallate (EGCG), showed sub-micromolar affinities. Although experimental studies are mandatory to fully understand the mechanisms behind PDGFRα inhibitors, the structural information obtained through this study could provide useful insight into the future development of more effective and targeted treatments for PDGFRα-related diseases, such as cancer and fibrosis."

Journal • Fibrosis • Immunology • Infectious Disease • Oncology • Scleroderma • Systemic Sclerosis • PDGFRA

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation. (PubMed, Mil Med Res) - "Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • LYN • MAPK8

SCREENING AND ANALYSIS OF POSSIBLE DRUGS BINDING TO PDGFRΑ: A MOLECULAR MODELING STUDY (EULAR 2023) - "Results Among these 27 compounds, the drugs Bafetinib, Radotinib, Flumatinib and Imatinib showed the higher affinity for this tyrosine kinase receptor, lying in the nanomolar order, while the natural products, such as curcumin, luteolin and EGCG, included in this group showed submicromolar affinities. All these compounds, through the QSAR and ADMET analysis, provided physicochemical information about an ideal best ligand for PDGFRα. Conclusion Although experimental studies are recommended, the structural information obtained could provide useful insight into the future development of PDGFRα inhibitors."

Infectious Disease • Oncology • PDGFRA

Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn. (PubMed, J Cell Mol Med) - "Lyn inhibitor Bafetinib and siRNA-lyn knockdown were administrated intrathecally to evaluate the effects of Lyn on pain thresholds, glycolysis and interferon regulatory factor 5 (IRF5) nuclear translocation of microglia in vivo and in vitro...Also, IRF5 promoted the binding of transcription factors SP1, PU.1 to glycolytic gene promoters, and then the enhanced glycolysis facilitated the proliferation and pro-inflammatory phenotype transition of microglia and contributed to neuropathic pain. Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn."

Journal • Neuralgia • Pain • IRF5 • LYN

Transcriptomic and enhancer landscape profiling identify Src-family kinase LYN as a candidate therapeutic target in human angiosarcoma (Sarcoma-RC 2023) - "Bafetinib, a known inhibitor of LYN kinase, was able to inhibit the viability of all tumor cell-lines in a dose-dependent manner at 72 hours (IC50 all between 5-10 μM), while decreasing protein expression of LYN and phospho-LYN...Our preliminary analysis of potential transcription factor binding identified candidate transcription factors responsible for regulating LYN expression. Legal entity responsible for the study The authors."

Angiosarcoma • Epstein-Barr Virus Infections • Oncology • Sarcoma • Solid Tumor • BCL2A1 • CXCL6 • LYN

Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer. (PubMed, Front Pharmacol) - "By using the CT26 tumor model, we further confirm that Bafetinib suppressed PD-L1 expression in vivo. In conclusion, our study shows that Bafetinib inhibits the transcription of PD-L1 through transcription factor c-Myc, suggesting that Bafetinib might be a small molecule drug targeting PD-L1."

IO biomarker • Journal • Lung Cancer • Oncology • Solid Tumor • MYC • PD-L1

Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation. (PubMed, Brief Bioinform) - "Two compounds, 7-hydroxystaurosporine and bafetinib, show synergistic antiviral effects in vitro and strongly inhibit viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, the relevant chemical substructures of the identified drugs are extracted to provide a chemical vocabulary that may help to design new effective drugs."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Development and Validation of a Five-RNA-Based Signature and Identification of Candidate Drugs for Neuroblastoma. (PubMed, Front Genet) - "The potential mechanisms of the five RNAs were also explored via gene set enrichment analysis, and candidate drugs targeting the five genes, including dabrafenib, vemurafenib, and bafetinib, were screened. In conclusion, we constructed a five-RNA-based signature to predict the survival of NBL and screened candidate agents against NBL."

Journal • Neuroblastoma • Oncology • Solid Tumor • MYCN

Patterns of Relapse in Small Cell Lung Cancer: Competing Risks of Thoracic versus CNS Relapse. (PubMed, Curr Oncol) - "Thoracic relapse and CNS relapse represent competing risks for patients with SCLC. Decisions about incorporating thoracic or CNS radiation are complex. More research is needed to incorporate performance status and LDH into treatment algorithms."

Journal • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

[VIRTUAL] IL-3 RESCUES MUTANT FLT3 AND KIT-POSITIVE AML CELLS FROM TARGETED THERAPY (EHA 2021) - "Especially, selective FLT3 inhibitors (quizartinib, sorafenib, midostaurin, etc) show significant clinical activity in AML patients...Combination of RTK inhibitors with SRC (bosutnib and bafetinib) and JAK2 (ruxolitinib), but not MAPK targeting drugs, abrogated IL-3 rescue-effect on AML cells...Studies with patient-derived xenotransplantation models are needed to clarify the findings. All in all, our study provides a rational for the use of RTK inhibitors in combination with agents blocking compensatory cytokine and growth factor signaling."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • FLT3 • KIT • NTRK1

[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021) - "Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119."

Pan tumor • Brain Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • LYN

[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021) - "Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119."

Pan tumor • Brain Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • LYN

[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021) - "Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119."

Pan tumor • Brain Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • LYN

[VIRTUAL] Pan-cancer analysis of SRC family kinases expression and sensitivity to SRC inhibitors. (EACR 2021) - "Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119."

Pan tumor • Brain Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • LYN

[VIRTUAL] Characterization and targeted therapy using patient tumor-derived 3-D spheroids in a metastatic castrate resistant prostate cancer model (AACR 2021) - "This tumor was obtained from a patient with mCRPC who progressed on enzalutamide, abiraterone, cabazitaxel, and had exposure to docetaxel, however discontinued due to toxicity...Single agents (abemaciclib, bafetinib, erdafitinib, tipifarnib, MK2206, APR-246) all caused dose dependent inhibition up to 100% inhibition. This rare prostate cancer model, GUR017M allows us to test novel single agents and combination strategies in 3-D culture. This patient tumor has also proven to be a successful PDTX model which allows for confirmatory testing in animal models in order to move forward with clinical trial proposals."

Clinical • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CCND1 • FGF3 • HRAS • LYN • TP53

A pan-cancer analysis of the HER family gene and their association with prognosis, tumor microenvironment, and therapeutic targets. (PubMed, Life Sci) - "These findings may elucidate the roles played by HER family gene in cancer progression and providing insights for further investigation of the HER family gene as potential targets in pan-cancer."

Biomarker • Journal • Pan tumor • Tumor microenvironment • Clear Cell Renal Cell Carcinoma • Head and Neck Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ERBB3 • ERBB4 • HER-2

Analysis of the role of Frizzled 2 in different cancer types. (PubMed, FEBS Open Bio) - "FZD2 influenced drug sensitivities, including to cobimetinib (r = -0.553, P< 0.001), selumetinib (r = -0.539, P < 0.001), bafetinib (r = - 0.538, P < 0.001), tamoxifen (r = -0.523, P < 0.001), alvespimycin (r = -0.520, P < 0.001), and nilotinib (r = -0.502, P < 0.001). FZD2 has the most significant correlation with ROR2 (r =0.4, P < 0.001), Wnt2 (r = 0.37, P < 0.001), and Wnt4A (r =0.34, P < 0.001). The results confirm the importance of FZD2 expression in cancer prognosis and treatment, and provide new clues for treatment strategies."

IO biomarker • Journal • Immune Modulation • Inflammation • Inflammatory Arthritis • Oncology • MSI • TMB

INNO-406 inhibits the growth of chronic myeloid leukemia and promotes its apoptosis via targeting PTEN. (PubMed, Hum Cell) - "In vivo study further confirmed that INNO-406 inhibited the growth of CML cells by targeting PTEN. Based on the above findings, this work extended our understanding of INNO-406 in the therapy of CML and its molecular mechanism."

IO Biomarker • Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • Sarcoma • Solid Tumor

Quercetin as a Lyn kinase inhibitor inhibits IgE-mediated allergic conjunctivitis. (PubMed, Food Chem Toxicol) - "This study illustrated the use of quercetin for the treatment of allergic conjunctivitis, which might act through its ability to inhibit Lyn/PLCγ/IP3R-Ca, Lyn/ERK1/2, and Lyn/NF-κB signaling. The inhibition of Lyn likely represents a major mechanism by which quercetin dampens the inflammatory response in AC disease models."

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