TRPML1 activation for pulmonary fibrosis research
exploratoryresearch program · medium · Thu Jan 01 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
Investigate whether TRPML1 regulates extracellular matrix protein turnover in lung fibrosis by controlling matrix metalloproteinase release.
Preclinical mechanistic research in mouse airways, lung macrophages, and fibroblast supernatants evaluating TRPML1 loss and small-molecule activation effects on MMP2, MMP8, MMP9, MMP12, and MMP19 release.
Publication reported in 2026 identifying TRPML1 as a regulator of MMP release in lung tissue, with TRPML1 loss producing a fibrosis-like lung phenotype in MLIV mice.
TRPML1 loss reduced MMP levels and was associated with excessive extracellular collagen and elastin accumulation; small-molecule activation increased MMP levels.
PHLYT autophagic degradation platform
undisclosedplatform · high · Tue Nov 15 2022 00:00:00 GMT+0000 (Coordinated Universal Time)
Initiate target-specific autophagic degradation of disease targets independent of target size or complexity, with potential applications in oncology, inflammation, neurodegeneration, and metabolic disorders.
Cellular degradation platform based on reprogramming the autophagy pathway, described as Phagosome-Lysosome Targeting.
Casma reported a $46.0 million Series C financing on 2022-11-15 to support its autophagy-based drug discovery and development work.
GABARAP-FLCN/FNIP-TFEB lysosomal biogenesis research
exploratoryresearch program · medium · Fri Jan 01 2021 00:00:00 GMT+0000 (Coordinated Universal Time)
Define how autophagy-related GABARAP signaling links autophagic flux and endolysosomal stress to TFEB/TFE3-driven lysosomal biogenesis.
Mechanistic cellular research on GABARAP conjugation to membranes, sequestration of the FLCN-FNIP tumor suppressor complex, RagC/D signaling, mTOR-dependent TFEB phosphorylation, and lysosomal capacity control.
Science Advances publication in 2021 described the GABARAP-FLCN/FNIP-TFEB axis as a molecular sensor coordinating lysosomal homeostasis with autophagy-lysosomal network perturbations.
GABARAP, but not LC3, was required for TFEB/TFE3 activation during CASM, Parkin-dependent mitophagy, and Salmonella-induced xenophagy; GABARAP binding disrupted FLCN/FNIP GAP function toward RagC/D and impaired mTOR-dependent TFEB phosphorylation.
TRPML1 antagonist analogs for cancer migration and invasion research
exploratoryresearch program · medium · Fri Jan 01 2021 00:00:00 GMT+0000 (Coordinated Universal Time)
Identify selective TRPML1 inhibitors and evaluate their effects on autophagy, TFEB translocation, and triple-negative breast cancer cell migration and invasion.
Small-molecule discovery and analog characterization of 17β-estradiol methyl ether and reduced-estrogen-receptor-activity analogs PRU-10 and PRU-12 as TRPML1 antagonists.
Scientific Reports publication in 2021 reported EDME as a potent isoform-selective TRPML1 antagonist and described PRU-10 and PRU-12 analogs.
EDME and analogs selectively affected TRPML1-linked autophagy induction and TFEB translocation and inhibited triple-negative breast cancer cell migration and invasion.
