Ghrelin is a stomach-derived peptide hormone which stimulates appetite. For ghrelin to exert its orexigenic effect, octanoylation on the serine-3 residue of this gut-brain peptide is essential. The octanoylation of ghrelin is mediated by a unique acyltransferase enzyme known as ghrelin O-acyltransferase (GOAT). Thus modulating this enzyme offers viable approaches to alter feeding behaviors. Over the past decade, several small-molecule based approaches have appeared dealing with the discovery of compounds able to modulate this enzyme for the treatment of obesity and type 2 diabetes. Drug discovery efforts from academic groups and several pharmaceutical companies have fielded compounds having efficacy in altering acylated ghrelin levels in animal models but to date, compounds modulating the activity of the GOAT enzyme do not yet represent clinical options.  https://www.selleckchem.com/MEK.html  This mini-review covers the drug discovery approaches of the last decade since the discovery of the GOAT enzyme.Pyrazolo[3,4-d]pyrimidines have become of significant interest for the medicinal chemistry community as a privileged scaffold for the development of kinase inhibitors to treat a range of diseases, including cancer. This fused nitrogen-containing heterocycle is an isostere of the adenine ring of ATP, allowing the molecules to mimic hinge region binding interactions in kinase active sites. Similarities in kinase ATP sites can be exploited to direct the activity and selectivity of pyrazolo[3,4-d]pyrimidines to multiple oncogenic targets through focussed chemical modification. As a result, pharma and academic efforts have succeeded in progressing several pyrazolo[3,4-d]pyrimidines to clinical trials, including the BTK inhibitor ibrutinib, which has been approved for the treatment of several B-cell cancers. In this review, we examine the pyrazolo[3,4-d]pyrimidines currently in clinical trials for oncology patients, as well as those published in the literature during the last 5 years for different anticancer indications.Traumatic coagulopathy due to severe external injury and internal hemorrhage is life-threatening to accident victims and soldiers on the battlefield, causing considerable number of deaths worldwide. Patients with inherited bleeding disorders (such as haemophilia, von Willebrand disease, inherited qualitative platelet defects, and afibrinogenemia) also contribute to the vast number of deaths due to abnormal bleeding, and these patients are difficult to handle during surgery. Platelets and different plasma proteins play an essential role in blood coagulation and in the maintenance of the body's hemostatic balance. The improper function or deficiency of these factors cause abnormal bleeding. To address such bleeding disorders, external clotting agents (such as extracellular protein-inspired natural and synthetic peptide-based sealants and peptide-functionalized polymer/liposome-based sealants) have been developed by different groups of researchers. The primary focus of this review is to provide molecular insights into the existing biologically inspired peptide-based sealants, highlighting the advantages and limitations of such reported designed sealants to handle blood clotting, and also provide insights into the design of improved next-generation surgical sealants.Neuraminidase, an abundant glycoprotein on the influenza virus surface, plays crucial roles in virus replication. Targeting neuraminidase could be a splendid way for the prevention of the spread of influenza infections. Herein, we have identified an octapeptide (errKPAQP) from a synthesized peptide library, originating from mimicking the binding pocket of oseltamivir in neuraminidase, as a potent peptide neuraminidase inhibitor. The docking-based virtual studies showed that errKPAQP exhibited a strong binding affinity (a docking score of -20.03) and nanomolar affinity (11 nM) to influenza neuraminidase, and can inhibit neuraminidase activity at a concentration as low as 4.25 μM, leading to effective protection of MDCK cells from influenza virus-induced death and replication. Furthermore, errKPAQP presented low hemolytic activity, minimal cytotoxicity, and good pharmacokinetic characteristics, which are imperative for an anti-influenza drug. Importantly, errKPAQP was capable of reducing influenza virus-induced inflammation, the serious damage to the lung tissues, and mortality rates in infected mice, indicating that it could protect against the lethal challenge of influenza viruses in vivo. Therefore, we have developed a novel neuraminidase peptide inhibitor with advantageous biological properties and high inhibitory activity towards neuraminidase, and it can serve as a promising anti-influenza drug.Activity cliffs (ACs) are pairs of structurally similar or analogous active compounds with large differences in potency against the same target. For identifying and analyzing ACs, similarity and potency difference criteria must be determined and consistently applied. This can be done in various ways, leading to different types of ACs. In this work, we introduce a new category of ACs by combining different similarity criteria, including the formation of matched molecular pairs and structural isomer relationships. A systematic computational search identified such ACs in compounds with activity against a variety of targets. In addition to other ACs exclusively formed by structural isomers, the newly introduced category of ACs is rich in structure-activity relationship (SAR) information, straightforward to interpret from a chemical perspective, and further extends the current spectrum of ACs.The discerning reactivity of sulfur(vi)-fluoride exchange (SuFEx) chemistry has enabled the context-specific labeling of protein binding sites by chemical probes that incorporate these versatile warheads. Emerging information from protein-probe structures and proteomic mapping experiments is helping advance our understanding of the protein microenvironment that dictates the reactivity of targetable amino acid residues. This review explores these new findings that should influence the future rational design of SuFEx probes for a multitude of applications in chemical biology and drug discovery.