BHG712 / Novartis - LARVOL DELTA

Identification of the Ephrin/Eph signaling pathway for combination therapies with CDK4/6 inhibitors in bladder cancer (DGU 2025) - "Inhibitors targeting CDK4/6 (Palbociclib, PD) and the Ephrin/Eph signaling pathway (ALW-II-41-27, ALW-II-49-7, NVP-BHG712, Dasatinib) were utilized. We identified the Ephrin/Eph signaling pathway as a novel specific therapeutic target for the treatment of bladder cancer. Combination with CDK4/6 inhibitors demonstrates enhanced therapeutic efficacy in bladder cancer."

Combination therapy • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • STING

Discovery of Genomic Targets and Therapeutic Candidates for Liver Cancer Using Single-Cell RNA Sequencing and Molecular Docking. (PubMed, Biology (Basel)) - "The proposed candidates include Adozelesin, Tivozanib, NVP-BHG712, Nilotinib, Entrectinib, Irinotecan, Ponatinib, and YM201636. This study provides critical insights into the genomic landscape of liver cancer and identifies promising therapeutic candidates, serving as a valuable resource for advancing liver cancer research and treatment strategies."

Journal • Hepatology • Liver Cancer • Oncology • Solid Tumor

Discovery of Novel Multiangiogenic Agents Targeting VEGFR2, EphB4, FGFR-1, and TIE-2: Receptor-Based Pharmacophore Modeling, Virtual Screening, and Molecular Modeling Studies. (PubMed, ACS Omega) - "Taking reference drugs sorafenib (VEGFR2), NVP-BHG712 (EphB4), pemiganitib (FGFR-1), and DP1919 (TIE-2), three promising natural compounds CNP0003920, CNP0243075, and CNP0211397 were concluded based on their end-point binding energies, binding interactions, molecular dynamics, and optimal pharmacokinetic and toxicity profiles. The density functional theory (DFT) results suggested that the identified compounds bound with protein complexes are stable. Our findings can represent a promising starting point for developing multimodal analogues VEGFR2, EphB4, FGFR-1, and TIE-2 proteins."

Journal • Oncology • EPHB4 • FGFR1 • KDR

Screening of common genomic biomarkers to explore common drugs for the treatment of pancreatic and kidney cancers with type-2 diabetes through bioinformatics analysis. (PubMed, Sci Rep) - "Finally, we identified six top-ranked drug molecules (NVP.BHG712, Irinotecan, Olaparib, Imatinib, RG-4733, and Linsitinib) as potential common treatments for PC, KC and T2D during their co-existence, supported by the literature reviews. Thus, this bioinformatics study provides valuable insights and resources for developing a genome-guided common treatment strategy for PC and/or KC patients who are also suffering from T2D."

Biomarker • Journal • Diabetes • Genito-urinary Cancer • Hepatology • Kidney Cancer • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor • Type 2 Diabetes Mellitus • BIRC5 • E2F7 • MUC1 • RRM2 • TOP2A

Tensile force promotes osteogenic differentiation via ephrinB2-EphB4 signaling pathway in orthodontic tooth movement. (PubMed, BMC Oral Health) - "TF promotes osteogenic differentiation through ephrinB2-EphB4 signaling and ERK1/2 pathway is a downstream of ephrinB2-EphB4 signaling partially mediate mediates TF-induced promotion of osteogenic differentiation."

Journal • EPHB4

Site-Specific Competitive Kinase Inhibitor Target Profiling Using Phosphonate Affinity Tags. (PubMed, Mol Cell Proteomics) - "Using the site-specific strategy to examine the on- and off-targets of the Ephrin receptor (Eph) B4 inhibitor NVP-BHG712 showed binding to EphA2 with an IC50 of 17 nM and EphB4 with an IC50 of 20 nM...Expanding the search to other amino acids revealed that XO44, in addition to 745 lysines, also covalently linked 715 tyrosines, which significantly expands the competitive ABPP search space and highlights the added value of the site-specific method. Therefore, the presented approach, which can be fully automated with liquid handling platforms, provides a straightforward, valuable new approach for competitive site-specific kinase inhibitor target profiling."

Journal • Oncology • DDR1 • EPHB4 • IMPDH2

NVP-BHG712 alleviates ovariectomy-induced osteoporosis by modulating osteoclastogenesis. (PubMed, Eur J Pharmacol) - "In the mouse model of ovariectomy-induced osteoporosis, NVP-BHG712 rescued bone loss by inhibiting excessive osteoclast activation. These findings suggest that NVP-BHG712 may be a promising treatment for pathological osteoporosis by alleviating osteoclast function."

Journal • Inflammation • Osteoporosis • Rheumatology • CTSK

A combination of cuproptosis and lncRNAs predicts the prognosis and tumor immune microenvironment in cervical cancer. (PubMed, Discov Oncol) - "In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer."

Journal • Tumor mutational burden • Cervical Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • TMB

Eph signal inhibition potentiates the growth-inhibitory effects of PLK1 inhibition toward cancer cells. (PubMed, Eur J Pharmacol) - "Here, we show that NVP-BHG712, an erythropoietin-producing human hepatocellular (Eph) signaling inhibitor, potentiates the growth-inhibitory effects of the PLK1 inhibitors BI2536 and BI6727 in cancer cells. These results suggest that Eph signal inhibition potentiates the effect of PLK1 inhibition, leading to strong mitotic arrest via SAC activation and the subsequent reduction of cancer cell survival. The combination of PLK1 inhibition and Eph signal inhibition will provide a new effective strategy for targeting cancer cell division."

Journal • Oncology

Comprehensive bioinformatics and experimental analysis of SH3PXD2B reveals its carcinogenic effect in gastric carcinoma. (PubMed, Life Sci) - "Our study strongly suggests that SH3PXD2B is a carcinogenic molecule that can be used as a biomarker for GC detection, prognosis, treatment design, and follow-up."

Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ADAM15 • SH3PXD2B

Optimization of the Lead Compound NVP-BHG712 as Colorectal Cancer Inhibitor. (PubMed, Chemistry) - "Testing in up to seven colon cancer cell lines that express EPHA2 reveals that several derivatives feature promising effects for control of human colon carcinoma. Thus, we have developed a set of powerful tool compounds for fundamental new research on the interplay of EPH receptors in a cellular context."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Infectious Disease • Oncology • Solid Tumor • EPHA2

Robust identification of common genomic biomarkers from multiple gene expression profiles for the prognosis, diagnosis, and therapies of pancreatic cancer. (PubMed, Comput Biol Med) - "Finally, we suggested KGs-guided five repurposable drug molecules (Linsitinib, CX5461, Irinotecan, Timosaponin AIII, and Olaparib) and a new molecule (NVP-BHG712) against PC by molecular docking. The cross-validation and some literature reviews also supported our findings. Therefore, the finding of this study might be useful resources to the researchers and medical doctors for diagnosis, prognosis and therapies of PC by the wet-lab validation."

Biomarker • Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • ADAM10 • ANXA2 • COL1A2 • ITGB1 • ITGB5