Intracranial Response to Selpercatinib After Pralsetinib-Induced Disease Progression in Rearranged During Transfection Fusion-Positive Non-Small-Cell Lung Cancer: Case Report.

RET fusion-positive NSCLC accounts for 1% to 2% of lung carcinoma cases. Although two Food and Drug Administration-approved selective RET inhibitors, pralsetinib, and selpercatinib, have revealed efficacy in managing RET fusion-positive NSCLC, this case series is unique in its focus on the intracranial response to selpercatinib after disease progression during pralsetinib treatment. This report contributes to the literature by providing evidence of selpercatinib's potential as a treatment option in such refractory cases.

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non-Small Cell Lung Cancer-Results from the Drug Rediscovery Protocol.

Purpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.

Patients And Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity.

Previously Published Phosphatase Probes have Limited Utility Due to their Unspecific Reactivity.

This study explores the use of activity-based protein profiling to study protein tyrosine phosphatases. With the discovery of allosteric SHP2 inhibitors, this enzyme family has resurfaced as interesting drug targets. Therefore, we envisioned that previously described direct electrophiles and quinone methide-based traps targeting phosphatases could be applied in competitive activity-based protein profiling assays.

Structure-Activity Relationship Studies of Aryl Sulfoxides as Reversible Monoacylglycerol Lipase Inhibitors.

Monoacylglycerol lipase (MAGL) is the key enzyme for the hydrolysis of endocannabinoid 2-arachidonoylglycerol (2-AG). The central role of MAGL in the metabolism of 2-AG makes it an attractive therapeutic target for a variety of disorders, including inflammation-induced tissue injury, pain, multiple sclerosis, and cancer. Previously, we reported , an aryl sulfoxide, as a peripherally restricted, covalent reversible MAGL inhibitor that reduced neuropathic pain and inflammation in preclinical models.