Search

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-L-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.

Background : Managing minor ailments in community pharmacy is an evolving pharmacy service in developing countries. Defined scopes of practice for pharmacy staff are essential for the safe management of minor ailments. Limited research exists regarding the perceptions of Indonesian pharmacists’ and pharmacy technicians’ scopes of practice in providing minor ailments management services. Objective : To evaluate pharmacists’ and pharmacy technicians’ understanding of their scopes of practice, perc eived competency and factors influencing the delivery of minor ailments services in Indonesian community pharmacies. Methods : Cross - sectional surveys were conducted during January - February 2020 of pharmacists and pharmacy technicians attending seminars co nducted by relevant Indonesian Associations in Central Java, Indonesia. Percentage of common responses (PCR) described similarity of perceived scopes of practice for pharmacists and pharmacy technicians. Univariate and multivariate analyses ide ntified asso ciations of scopes of practice with pharmacy characteristics. Results : A total of 185 pharmacists and 142 pharmacy technicians participated. Pharmacy technicians performed minor ailment consultations, however, if considered beyond their scope of practice, they referred the patient to the pharmacist (T=120/142, 84.5%). Vaginal thrush, bacterial conjunctivitis, gastro - oesophageal reflux disease, and acute pain were minor ailments perceived only within a pharmacist’s scope (PCR above 60%). Of 34 minor ailments , 11 showed PCR values between 40 - 60% overlapping pharmacists and pharmacy technicians perceived scopes of practice (allergy/rash, back pain, cold sores, dermatitis, diarrhoea, eczema, hayfev er, haemorrhoids, rheumatism, sore throat, and superficial wounds ). Back pain, cold sores, dermatitis, and sore throat associated pharmacists’ scope of practice with years of practice experience (p - value<0.05). Pharmacy technicians perceived their scopes of practice