https://www.selleckchem.com/products/nmda-n-methyl-d-aspartic-acid.html The rule of 5 was designed to estimate the likelihood of poor absorption or permeation, noting the impact of poor solubility. This Perspective explores the impact of various physicochemical descriptors and contemporary lipophilicity measurements on permeability and solubility, showing that the distribution coefficient log D7.4 (rather than log P) is the most impactful parameter. Molecular weight, almost invariably the defining characteristic of "beyond the rule of 5" compounds, has little impact on solubility when log D7.4 measurements and aromaticity are considered. Predicting permeation is more complex, given passive and carrier transport mechanisms; however, notable patterns of behavior are apparent, giving insight even "beyond the rule of 5". Recommended best practices should involve using the facts (measurements) and the patterns they reveal to establish informative principles rather than fastidious rules.p62/SQSTM1, encoded by gene SQSTM1, is widely known as an adaptor protein of selective autophagy to promote aggregate-prone proteins for degradation. It is also a stress-induced scaffold protein involved in Nrf2 activation to resist oxidative stress. Multiple domains of p62 interact with several essential pathways implicated in cell differentiation and proliferation, placing p62 at a significant position to mediate cell survival and apoptosis. The p62 protein has been suggested as a potential target in recent years, since its abnormal expression or SQSTM1 gene mutation is tightly associated with various diseases including cancer such as hepatocellular carcinoma and prostate cancer, neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis, atherosclerosis, and Paget's disease of bone. In this review, we will discuss the relationship between p62 and these diseases, and we attempt to put forward novel methods for current diagnosis or therapy by regulating the