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https://www.selleckchem.com/screening/kinase-inhibitor-library.html Dysregulation of the mechanistic target of rapamycin (mTOR) pathway is implicated in cancer and neurological disorder, which identifies mTOR inhibition as promising strategy for the treatment of a variety of human disorders. First-generation mTOR inhibitors include rapamycin and its analogues (rapalogs) which act as allosteric inhibitors of TORC1. Structurally unrelated, ATP-competitive inhibitors that directly target the mTOR catalytic site inhibit both TORC1 and TORC2. Here, we review investigations of chemical scaffolds explored for the development of highly selective ATP-competitive mTOR kinase inhibitors (TORKi). Extensive medicinal chemistry campaigns allowed to overcome challenges related to structural similarity between mTOR and the phosphoinositide 3-kinase (PI3K) family. A broad region of chemical space is covered by TORKi. Here, the investigation of chemical substitutions and physicochemical properties has shed light on the compounds' ability to cross the blood brain barrier (BBB). This work provides insights supporting the optimization of TORKi for the treatment of cancer and central nervous system disorders. Adipose tissue (AT) senescence is associated with AT dysfunction in rodents, but little is known about human AT senescence. The study goal was to define the distribution of senescent cells in two subcutaneous depots and understand relationships with adiposity and inflammation. Sixty-three volunteers (48 females) underwent abdominal and femoral subcutaneous fat biopsies. Fat cell size, senescent cells using senescence-associated β-galactosidase staining per 100 nucleated cells (percentage), and mRNA expression of four cytokines were measured. There was a larger proportion of senescent cells in femoral than abdominal subcutaneous AT (mean difference 1.6% [95% CI 0.98%-2.3%], p<0.001), and the percentage of femoral AT senescent cells was greater in women than men (median 3.9% vs. 2.1%,

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