PLD-101 / PeLeMed - LARVOL DELTA

Overcoming resistance in RET-altered cancers through rational inhibitor design and combination therapies. (PubMed, Bioorg Chem) - "Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g., V804L/M, G810C/S/R), both of which limit their clinical application...To overcome drug resistance, the design strategies of novel inhibitors focus on multi-target inhibition (such as PLM-101 targeting RET/YES1/FLT3, TPX-0046 targeting RET/SRC), structural optimization (such as helical ring derivatives enhancing binding stability), and natural compound screening (such as ZINC series molecules)...For instance, selpercatinib combined with crizotinib can inhibit MET amplification-driven resistance, while arsenic trioxide combined with pralsetinib restores sensitivity by inhibiting the HH-Gli pathway. Current clinical trials show that novel RET inhibitors such as SY-5007 have a significant objective response rate in advanced RET..."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR • FLT3 • MET • RET • STAT1

Therapeutic strategy using novel RET/YES1 dual-target inhibitor in lung cancer. (PubMed, Biomed Pharmacother) - "In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer."

Journal • Lung Cancer • Oncology • Solid Tumor • ALK • CCDC6 • CTTN • EGFR • KRAS • RET

PLM-101 is a novel and potent FLT3/RET inhibitor with less adverse effects in the treatment of acute myeloid leukemia. (PubMed, Biomed Pharmacother) - "However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure...This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML."

Adverse events • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • RET