TGRX-3247 / Shenzhen TargetRx - LARVOL DELTA

Global proteomic profiling of tgrx-3247,a heterobifunctional degrader for the treatment of BCR::ABL1-driven chronic myeloid leukemia (ASH 2025) - "We then treated LAMA-84 and KCL22s cells with TGRX-3247 along with the warhead, a non-degrader methyl analog, asciminib and ponatinib. Of note, our proteomics study reconsolidated previous discoveries on BCR::ABL1 functions,such as in p27Kip1 regulation through the SKP2 pathway, as well as in lysosome and autophagy. Moreinformation of TGRX-3247 is worth mining to bring new insights to the biology of CML, which mayultimately lead to novel treatments for CML patients."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Targeted Protein Degradation • ABL1 • ABL2 • ANXA5 • CDCA5 • CDKN1B • CRBN • GSPT1 • IKZF1 • PLK1 • SKP2 • ZMYM2

An Orally Active Pan-BCR::ABL1 Degrader Tgrx-3247 Potently Targets a Wide Spectrum of Orthosteric, Allosteric and Compound Mutations Resistant to TKI Therapies (ASH 2024) - "Proteasome inhibitors such as MG132 and bortezomib blocked the degradation. With such potent and continuous depletion of the oncogenic signaling, coupled with a wide range of mutant coverage, TGRX-3247, as a targeted protein degrader, may potentially bring clinical benefits that are unseen with previous TKIs, including improved DMR, TFR rates, and even the possibility of functional cure. Its potential clinical application for CML patients is worth further investigation."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Oral Cancer • Targeted Protein Degradation • ABL1 • CRBN • STAT5