Effects of ALK2 inhibitors on viability in DMG/DIPG patient-derived cells

Diffuse Intrinsic Pontine Glioma (DIPG) is a rare and aggressive pediatric cancer located in the pons region of the brainstem, classified as a broader class of H3 K27M mutant Diffuse Midline Gliomas (DMG). Traditional drug development models struggle to address rare diseases like DIPG due to small patient populations and high risks. M4K Pharma focuses on developing an ALK2 enzyme inhibitor, the first therapeutic designed specifically for DIPG. We are leveraging highly potent, selective, and drug-like molecules targeting this protein to create a promising therapeutic option for children affected by this devastating disease. This dataset contains in vitro dose-response and cell viability results for a panel of M4K compounds tested across multiple DIPG cell lines. The experiments measure changes in cell number following compound treatment. and include both ACVR1-mutant (SU_DIPG_4N, SU_DIPG_36, HSJD_DIPG_007, ICR_B181) and ACVR1 wild type (SU_DIPG_VI and SU_DIPG_33) cell lines. The dataset includes comparative analyses of compounds M4K2009 and M4K2308 across the DIPG cell line panel, with dose-response curves reporting cell number as a percentage of untreated controls across increasing compound concentrations. Additional experiments assess a broader panel of compounds, including M4K2009, M4K2045, M4K2117, M4K2163, M4K2281, M4K2306, M4K3159, and M4K3228. For each compound and cell line combination, dose-response curves and corresponding GI50 values are provided and stratified by ACVR1 mutation status. Overall, the dataset provides a comparative in vitro characterization of growth inhibition profiles for multiple M4K ALK2 inhibitors across ACVR1-mutant and ACVR1-wild-type DIPG models. Table of key terms and definitions of the project. Key term Definition Diffuse Intrinsic Pontine Glioma (DIPG) A rare, aggressive pediatric brain tumor located in the pons region of the brainstem (median survival 9-12 months). Diffuse midline glioma (DMG) Broader classification of aggressive midline brain tumors associated with H3K27M mutations. ACVR1 Gene encoding the ALK2 kinase; activating gain-of-function mutations present in ~25-30% of DIPG cases. ALK2 A BMP type I receptor serine/threonine kinase that drives aberrant signaling in ACVR1-mutant DIPG. BMP signalling Bone morphogenetic protein pathway involved in cell differentiation and growth; dysregulated in ACVR1-mutant tumors. H3K27M mutation A histone mutation commonly found in DMG/DIPG that alters epigenetic regulation and tumor biology. M4K2009 Lead small-molecule, ALK2 inhibitor selected for IND-enabling development. SMAD1/5 phosphorylation Downstream signaling event of ALK2 activation; reduced phosphorylation indicates target engagement. Orthotopic mouse model In vivo tumor model where DIPG cells are implanted in the brainstem to mimic human disease. RCAS-ACVR1 model Genetically engineered mouse model expressing ACVR1 and H3K27M mutation to study DIPG.