LX7101 / Lexicon Pharma - LARVOL DELTA

Microscale Thermophoresis for Thermodynamic Analysis: A Proof-of-Concept Study on LIMK Inhibitors. (PubMed, J Mol Biol) - "LIMK1 and its kinase domain (Kin1) showed comparable binding behavior to TH-257 and LX7101 (ΔG37°C = -10.3 ± 0.4 kcal mol-1), whereas LIMK2 interactions were significantly weaker (ΔG37°C lower by ∼1.5 kcal mol-1). Binding was enthalpy-driven, with entropy opposing complex formation, highlighting opportunities for rational optimization of inhibitors. This work establishes MST as a user-friendly, purification-free platform for deriving protein-ligand thermodynamics directly in cell lysates, providing a versatile proof-of-concept approach for studying challenging targets and guiding the development of therapeutically relevant inhibitors."

Journal

LIM kinase/inhibitor binding study in cell lysates using microscale thermophoresis in the red spectrum. (PubMed, Anal Chim Acta) - "Notably, sub-micromolar Kd values were confirmed for the reference inhibitors LX7101, BMS-5, and TH-257, with slight differences observed between full-length LIMKs and their kinase domains - differences often overlooked in the literature...miRFP670 operates in a spectral region (red) with minimal cellular autofluorescence, enhancing signal specificity and sensitivity. This approach offers a straightforward and broadly applicable, purification-free platform for early-stage drug discovery."

Journal

Should we keep rocking? Portraits from targeting rho kinases in cancer. (PubMed, Pharmacol Res) - "Alternatively, we highlight and discuss detrimental effects of ROCK inhibition provoked not only by the action on off-targets, but most importantly, by pro-survival effects on cancer stem cells, dormant cells, and circulating tumor cells, along with cell-context or microenvironment-dependent contradictory responses. Together these drawbacks represent a risk for cancer cell dissemination and metastasis after anti-ROCK intervention, a caveat that should concern scientists and clinicians."

Journal • Review • Ewing Sarcoma • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor • Wilms Tumor • CTCs

Loss of the fragile X mental retardation protein causes aberrant differentiation in human neural progenitor cells. (PubMed, Sci Rep) - "Interestingly, the aberrant expression of GFAP and the impaired firing was corrected by treatment with the protein kinase inhibitor LX7101. These findings underscore the modulatory roles of FMRP in human neurogenesis, and further demonstrate that the defective phenotype of FXS could be reversed at least partly by small molecule kinase inhibitors."

Journal