JNJ-38877605 / J&J - LARVOL DELTA

Targeting MET Signalling Activated by CPNE3-RACK1 Interaction Through VWFA Domain to Suppress Lung Cancer Progression. (PubMed, J Cell Mol Med) - "The in vitro and in vivo functions of the MET inhibitor JNJ-38877605 were investigated...CPNE3 could interact with RACK1 through the VWFA domain and activate MET signalling. These findings may provide new insights into the development of novel therapeutic strategies for NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CPNE3 • RACK1

Food for thought: Effect of a high-fat meal on DO-2, a novel MET-kinase inhibitor (ESMO 2025) - P1 | "DO-2 is a redeveloped deuterated version of JNJ-38877605 to reduce toxic metabolite formation via AOX-1. Since an 8–10 hour ToT is ideal for efficacy and toxicity, food optimises the pharmacokinetic profile of DO-2, which is further evaluated in the extension phase of the phase 1 study in patients. Potentially, EGCG could reduce M3 formation."

Oncology • Solid Tumor

A High-Fat Meal Optimizes the Pharmacokinetic Profile of DO-2, a Novel MET-Kinase Inhibitor for NSCLC (IASLC-WCLC 2025) - P1 | "DO-2 is a deuterated version of JNJ-38877605, redesigned to reduce toxic metabolite (M5) formation via AOX-1...Total exposures (AUC 0-24h ) to DO-2, DO-5 and M3 are similar with and without food. Since an 8-10 hour ToT is ideal for efficacy and toxicity, food optimizes the pharmacokinetic profile of DO-2, which is further evaluated in the extension phase of the phase 1 study in patients (NCT05752552). Possibly, EGCG could reduce M3 formation and should be studied further."

PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MET

Deciphering the role of MET/NMDAR complex in colorectal cancer pathogenesis (EACR 2025) - "To understand the biological role of this crosstalk in the HGF-driven invasive program, matrigel invasion and wound healing assays were performed in presence of two specific NMDAR (MK801 and Ifenprodil) and MET (JNJ-38877605) inhibitors. Overall, these data emphasize that MET/NMDAR crosstalk is involved in the CRC invasive program, suggesting that a combinatorial therapy targeting this complex may be exploited as a new therapeutic strategy."

Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • APC • GRIN2B • GRIN2D • MET

The Receptor Tyrosine Kinase c-Met Promotes Lipid Accumulation in 3T3-L1 Adipocytes. (PubMed, Int J Mol Sci) - "JNJ38877605 (JNJ) is an inhibitor of c-Met with anti-tumor activity...JNJ further reduced the expression of adipogenic regulators, including CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), and perilipin A. Moreover, JNJ treatment increased cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) phosphorylation but decreased ATP levels. Significantly, KD of c-Met suppressed fat accumulation and triglyceride (TG) quantity and reduced the expression of C/EBP-α, PPAR-γ, FAS, ACC, and perilipin A. Collectively, the present results demonstrate that c-Met is a novel, highly conserved mediator of adipogenesis regulating lipid accumulation in murine adipocytes."

Journal • Oncology • AMPK • FASN • MET • PLIN2 • PPARA

Dynasore potentiates c-Met inhibitors against hepatocellular carcinoma through destabilizing c-Met. (PubMed, Arch Biochem Biophys) - "To improve the efficacy of c-Met inhibitors towards hepatocellular carcinoma, we investigated the combined effects of the dynamin inhibitor dynasore with several c-Met inhibitors, including tivantinib, PHA-665752, and JNJ-38877605. Mechanically, the combinatorial treatments decreased c-Met levels and hence markedly disrupted downstream signaling, as revealed by the dramatically declined phosphorylation of AKT and MEK. Taken together, our findings demonstrate that the candidate agent dynasore potentiated the inhibitory effects of c-Met inhibitors against hepatoma cells and will shed light on the development of novel therapeutic strategies to target c-Met in the clinical management of hepatocellular carcinoma patients."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Evaluation of Deuterium Labeled JNJ38877605: Pharmacokinetic, Metabolic, and In Vivo Antitumor Profiles. (PubMed, Chem Res Toxicol) - "Moreo-ver, after oral administration to the EBC-1 tumor-bearing nude mice, compound 3 exhibited a better antitumor efficacy than JNJ38877605. In conclusion, deuteration on the AO metabolic site of JNJ38877605 improved its AO metabolism, oral exposure, as well as in vivo antitumor efficacy."

Journal • PK/PD data