Discovery and molecular basis of subtype-selective cyclophilin inhibitors.

Although cyclophilins are attractive targets for probing biology and therapeutic intervention, no subtype-selective cyclophilin inhibitors have been described. We discovered novel cyclophilin inhibitors from the in vitro selection of a DNA-templated library of 256,000 drug-like macrocycles for cyclophilin D (CypD) affinity. Iterated macrocycle engineering guided by ten X-ray co-crystal structures yielded potent and selective inhibitors (half maximal inhibitory concentration (IC50) = 10 nM) that bind the active site of CypD and also make novel interactions with non-conserved residues in the S2 pocket, an adjacent exo-site. The resulting macrocycles inhibit CypD activity with 21- to >10,000-fold selectivity over other cyclophilins and inhibit mitochondrial permeability transition pore opening in isolated mitochondria. We further exploited S2 pocket interactions to develop the first cyclophilin E (CypE)-selective inhibitor, which forms a reversible covalent bond with a CypE S2 pocket lysine, and exhibits 30- to >4,000-fold selectivity over other cyclophilins. These findings reveal a strategy to generate isoform-selective small-molecule cyclophilin modulators, advancing their suitability as targets for biological investigation and therapeutic development.

Comparative analysis of the antibacterial efficacy and bioactive components of Thuja occidentalis obtained from four different geographical sites.

The purpose of this study was to determine whether or not there were significant differences in the antibacterial potential of Thuja occidentalis collected from four distinct geographical sites, namely Chamba (Himachal Pradesh, India), Jalandhar (Punjab, India), Aurangabad (Bihar, India) and Kakching (Manipur, India). The plant extracts were prepared in three different solvents: ethanol, methanol, and acetone. The antibacterial potential of the plant extracts was tested against five different bacterial species using well diffusion test. The minimum inhibitory and bactericidal concentrations of the plant sample exhibiting maximum zone of inhibition against different bacterial strains were calculated. Further, the total phenols, flavonoids, and antioxidant efficacy (using DPPH assay) were also analysed biochemically. The activity of different antioxidant enzymes including SOD, CAT and APX were also recorded as these enzymes protect the cells from free radical damage. GC-MS analysis was also performed on all plant extracts to identify the bioactive components. The results showed that the T. occidentalis collected from the Kakching, Manipur, East side of India showed the highest zone of inhibition against all the bacterial strains, followed by Chamba, Jalandhar, and lastly Aurangabad. To analyse the impact of phytochemicals on the antibacterial efficacy, a correlation was drawn between the biochemical parameters and zone of inhibition using Karl Pearson's method. Most bacterial species demonstrated a positive correlation between antibacterial effectiveness (zone of inhibition) and biochemical markers. The GC-MS study revealed positive correlation between zone of inhibition and peak area percentages of α-Pinene, ß-caryophyllene, Germacrene-D, and Humulene in all bacterial species indicating that these chemicals may play a key role in the bactericidal potential of T. occidentalis. Based on the results of this investigation, it is evident that the antibacterial effectiveness of T. occidentalis varies with its geographical location which may be attributed to the differences in the phytochemical makeup.

Human monkeypox: epidemiology, transmission, pathogenesis, immunology, diagnosis and therapeutics.

"Zoonoses" describe diseases that may be acquired by humans from animals. Due to the constant contact between humans and other animals, many infectious diseases are disseminated. This may happen via direct contact, such as bites or scratches, or by indirect contact, such as when eating bush meat or using contaminated animal parts. Monkeypox disease is one such zoonotic infection which is now emerging as a disease of global concern, and the World Health Organization has already labelled it a public health emergency. The virus is related to other orthopox viruses and may be further classified into two genetically separate clades, the West African and the Central African. The latter is far more pathogenic than the former. Utilizing virotransducer and virostealth proteins, the virus is able to control the host's T-cell-mediated responses and impede the release of cytokines and chemokines.Monkeypox may be treated with tecovirimat, cidofovir, or brincidofovir, and prevention with the vaccination JYNNEOS is recommended. The disease's fast global expansion warrants concern despite the fact that it is less fatal than that caused by the variola virus. Before the sickness reaches catastrophic proportions, we must draw on our prior experiences and act prudently. This article serves as an introduction to the monkeypox virus and its associated pathology, treatments, diagnostics, and preventative measures.

Portrayal of Suicide in Bollywood Movies Over Last Two Decades: A Content Analysis.

Aim: To analyse Bollywood movies depicting suicides, released in last two decades, on content and scientific accuracy. Methodology: Online movie databases, blogs were accessed along with Google search to compile a list of movies portraying suicide (thought, plan, or act) in at least one character. Each movie was screened twice for details of character, symptoms, diagnosis, treatment, and scientific accuracy of depiction. Results: Twenty-two movies were analyzed. Most characters were middle-aged, unmarried, well educated, employed and affluent. Most common motives were emotional pain and guilt/shame. Most suicides were impulsive, method of choice was fall from height and resulted in death. Conclusion: Cinematic depiction of suicide may promote misconceptions among viewers. Alignment of cinematization with scientific knowledge is needed.

Rapid surveillance of COVID-19 by timely detection of geographically robust, alive and emerging hotspots using Particle Swarm Optimizer.

A novel virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a pandemic called Coronavirus disease 2019 (COVID-19). According to the World Health Organization, COVID-19 was first detected in Wuhan city in December 2019 and has affected 216 countries with 9473214 confirmed cases and 484249 deaths globally as on June 26th, 2020. Also, this outbreak continues to grow in many countries like the United States of America (U.S.), Brazil, India, and Russia. To ensure rapid surveillance and better decision-making by government authorities in different countries, it is vital to identify alive and emerging hotspots within a country promptly. State-of-the-art methods based on space-time scan statistics (like SaTScan) are not geographically robust. Also, due to the enumeration of many Spatio-temporal cylinders, the computation cost of Spatio-temporal SaTScan (ST-SaTScan) is very high. In the applications like COVID-19 where we need to detect the emerging hotspots daily as soon as the new count of cases gets updated, ST-SaTScan seems inefficient. Therefore, this paper proposes a Particle Swarm Optimizer-based scheme to timely detect geographically robust, alive, and emerging COVID-19 hotspots in a country. Timely detection can help government officials design better control strategies like increasing testing in hotspots, imposing stricter containment rules, or setting up temporary hospital beds. Performance of ST-SaTScan and proposed scheme have been analyzed for four worst-hit U.S. states for the incubation period of 14 days between June 11th, 2020, and June 24th, 2020. Results indicate that the proposed scheme detects hotspots of a higher likelihood ratio (a measure to indicate the significance of hotspot) than ST-SaTScan in significantly less time. We also applied the proposed scheme to detect the emerging COVID-19 hotspots in all states of the U.S. During the study period, the proposed scheme has detected 104 emerging COVID-19 hotspots.

Co-crystal structures of PTK6: With Dasatinib at 2.24 Å, with novel imidazo[1,2-a]pyrazin-8-amine derivative inhibitor at 1.70 Å resolution.

Human Protein tyrosine kinase 6 (PTK6)(EC:2.7.10.2), also known as the breast tumor kinase (BRK), is an intracellular non-receptor Src-related tyrosine kinase expressed five-fold or more in human breast tumors and breast cancer cell lines but its expression being low or completely absent from normal mammary gland. There is a recent interest in targeting PTK6-positive breast cancer by developing small molecule inhibitor against PTK6. Novel imidazo[1,2-a]pyrazin-8-amines (IPA) derivative compounds and FDA approved drug, Dasatinib are reported to inhibit PTK6 kinase activity with IC50 in nM range. To understand binding mode of these compounds and key interactions that drive the potency against PTK6, one of the IPA compounds and Dasatinib were chosen to study through X-ray crystallography. The recombinant PTK6 kinase domain was purified and co-crystallized at room temperature by the sitting-drop vapor diffusion method, collected X-ray diffraction data at in-house and resolved co-crystal structure of PTK6-KD with Dasatinib at 2.24 Å and with IPA compound at 1.70 Å resolution. Both these structures are in DFG-in & αC-helix-out conformation with unambiguous electron density for Dasatinib or IPA compound bound at the ATP-binding pocket. Relative difference in potency between Dasatinib and IPA compound is delineated through the additional interactions derived from the occupation of additional pocket by Dasatinib at gatekeeper area. Refined crystallographic coordinates for the kinase domain of PTK6 in complex with IPA compound and Dasatinib have been submitted to Protein Data Bank under the accession number 5DA3 and 5H2U respectively.

Crystal structures of monkey and mouse nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl nicotinamide.

Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-l-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT. It is known that the primary endogenous product catalyzed by NNMT, MNA is a specific inhibitor of NNMT. Our data clearly indicates that the MNA binds to the active site and it would be trapped in the active site due to the formation of the bridge between the pole (long helix, α3) and long C-terminal loop. This might explain the mechanism of MNA acting as a feedback inhibitor of NNMT.

Crystal structure of the kinase domain of human protein tyrosine kinase 6 (PTK6) at 2.33 Å resolution.

Human Protein tyrosine kinase 6 (PTK6) (EC:2.7.10.2), also known as the breast tumor kinase (BRK), is an intracellular non-receptor Src-related tyrosine kinase expressed in a majority of human breast tumors and breast cancer cell lines, but its expression is low or completely absent in normal mammary glands. In the recent past, several studies have suggested that PTK6 is a potential therapeutic target in cancer. To understand its structural and functional properties, the PTK6 kinase domain (PTK6-KD) gene was cloned, overexpressed in a baculo-insect cell system, purified and crystallized at room temperature. X-ray diffraction data to 2.33 Å resolution was collected on a single PTK6-KD crystal, which belonged to the triclinic space group P1. The Matthews coefficient calculation suggested the presence of four protein molecules per asymmetric unit, with a solvent content of ∼50%.The structure has been solved by molecular replacement and crystal structure data submitted to the protein data bank under the accession number 5D7V. This is the first report of apo PTK6-KD structure crystallized in DFG-in and αC-helix-out conformation.

Multifaceted and personalized therapy of advanced prostate cancer.

PURPOSE OF REVIEW: A number of molecular and genomic biomarkers that possess the ability to guide treatment or 'actionable targets' are being reported in metastatic prostate cancer. In addition, pathways of resistance to existing therapies and novel agents to overcome them are currently under active investigation. The next wave of investigations is focused on personalized therapy of prostate cancer. The focus of this review article is to provide an update on clinical development in advanced prostate cancer and to highlight the ongoing investigations of biomarker discovery, and ways of overcoming therapeutic resistance. The next generation of clinical trials developing novel targets and compounds promises to be in populations enriched with specific marker expression. RECENT FINDINGS: The breakthrough report, of the ability of the androgen receptor variant 7 mutation, detected in circulating tumor cells, to predict the lack of response to abiraterone or enzalutamide, and the remarkable responses of poly adenosine diphosphate ribose polymerase inhibitors in prostate cancer with DNA repair mutations have elevated hopes of a bright future in the biomarker-driven therapeutic arena. Novel targets such as bromodomain extra terminal-1 and phosphatidylinositol 3-kinase hold promise for the possibility of overcoming resistance. Novel hormone agents are also under active study. SUMMARY: As the clinical application of the multifaceted therapies narrows down to enriched patient populations selected by genomic testing, the therapeutic efficiency will escalate considerably. Novel targets, resistance mechanisms and relevant agents are being avidly tested, and the dream of personalized medicine is emerging into reality.

A phase II trial of ganetespib, a heat shock protein 90 Hsp90) inhibitor, in patients with docetaxel-pretreated metastatic castrate-resistant prostate cancer (CRPC)-a prostate cancer clinical trials consortium (PCCTC) study.

INTRODUCTION: Heat shock protein 90 (Hsp90) has been studied as a therapeutic target in many cancers. In preclinical trials, the Hsp90 ATPase inhibitor ganetespib demonstrated potent inhibition of solid tumor growth, with superior potency than prior Hsp90 inhibitors. Given the promising preclinical outcome and favorable pharmacologic properties of ganetespib, we conducted a phase II trial of single-agent ganetespib in patients with metastatic, castrate-resistant prostate cancer (mCRPC). The primary objective of the study was to determine the 6-month progression-free survival (PFS) rate. METHODS: Patients with mCRPC who had been previously treated with docetaxel were enrolled after meeting eligibility criteria. All patients received ganetespib at 200 mg/m(2) on days 1, 8, and 15 of every 28 days (one cycle). Subjects who tolerated therapy were continued on ganetespib until disease progression. Considering that Hsp90 acetylation may confer insensitivity to Hsp90 inhibitors and maspin inhibits protein deacetylation, maspin-associated molecular markers were evaluated. RESULTS: Eighteen patients were recruited into the trial; most were Caucasian, had performance status 1, had received prior docetaxel, and were heavily pretreated. Of the 17 patients who were treated, none attained 6-month PFS. Only 2 patients achieved PFS > 4 months. The median PFS was 1.9 months. As per the study design, the trial was terminated after the interim analysis. The most frequent types of Grade 3 toxicity were dehydration, diarrhea, and fatigue. Molecular markers provided little additional insight regarding drug activity. CONCLUSIONS: Ganetespib demonstrated minimal clinical activity in men with mCRPC. The true 6-month PFS rate was, at most, 0.20. Possible reasons for this include selection of a heavily pretreated patient population and lack of agent potency in patients with mCRPC.

Predictive and Prognostic Biomarkers in Non-Small Cell Lung Cancer.

Therapy of non-small cell lung cancer (NSCLC) patients has evolved over the past few years with the incorporation of targeted therapy and immune therapy. These changes have increased the importance of prognostic and predictive biomarkers to enable practicing physicians in making the most appropriate treatment decisions for NSCLC patients. A variety of prognostic factors based on clinical and pathologic features determine the overall outcome of the patient and these factors do influence decisions regarding initiation of therapy. The most important prognostic factors remain stage of the disease at diagnosis and performance status. For years, the only approved systemic therapy for NSCLC patients was chemotherapy. Despite attempts at defining factors that influence efficacy of chemotherapeutic agents, pemetrexed is the only chemotherapy drug that has differential activity based on a specific factor. In recent years, there is increasing focus on defining the molecular alterations critical to the oncogenic phenotype of NSCLC and targeting these alterations for therapeutic benefit. In addition, there is increasing use of immune-modulating drugs, specifically anti-PD-1 drugs, in advanced NSCLC patients. Several studies have shown that the probability of clinical benefit from these agents is greater in patients with NSCLCs that express PD-L1. The totality of these data suggests that determination of predictive markers prior to initiation of therapy is critical.

The structure of XIAP BIR2: understanding the selectivity of the BIR domains.

XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain-caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3-caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2-caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized; peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2-tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.

A Rare Case of Pulmonary Cavitary Disease Caused by Mycobacterium xenopi.

Mycobacterium xenopi is a slow-growing, acid-fast, non-tuberculous mycobacterium (NTM). It is often considered to be a saprophyte or an environmental contaminant. Mycobacterium xenopi has low pathogenicity and is usually seen in patients with pre-existing chronic lung diseases and immunocompromised patients. We present a case of Mycobacterium xenopi causing a cavitary lesion in a patient with chronic obstructive pulmonary disease (COPD) that was discovered incidentally during the low-dose CT scan done for lung cancer screening in a patient with COPD. The initial workup was negative for NTM. An Interventional-guided (IR) core needle biopsy was done given the high suspicion for NTM and revealed a positive culture for Mycobacterium xenopi.  Our case highlights the importance of considering NTM in the differential diagnosis of at-risk patients and pursuing invasive testing if there is a high clinical suspicion.

Tick-Borne Rhabdomyolysis: A Rare Case of Rhabdomyolysis and Acute Kidney Injury Due to Anaplasmosis.

Anaplasmosis is a tick-borne illness commonly seen in the northeastern states of the United States. The most common presenting signs are fever, malaise, and body aches accompanied by leukopenia, thrombocytopenia, and transaminitis. Rhabdomyolysis and acute kidney injury are rare presentations that can lead to significant morbidity.  We present the case of a patient who presented with non-specific symptoms of malaise, fatigue, and body aches and was found to have rhabdomyolysis and acute kidney injury on laboratory workup. A presumptive diagnosis of anaplasmosis was made, and the patient was started on treatment for the same. The patient recovered successfully. Our case highlights the rare presentation of anaplasmosis with rhabdomyolysis and acute kidney injury. Physician awareness is needed for early diagnosis and preventing morbidity.

Use of cauliflower mosaic virus DNA markers to assess the potential for pathogen transmission from physicians' white coats.

In an observational study, the sleeves and pockets of physicians' white coats often directly or indirectly contacted patients and environmental surfaces. DNA markers on the sleeves or pockets were frequently transferred to surfaces and patients. These findings suggest that contaminated white coats have the potential to contribute to pathogen transmission.

Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance.

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD8+ and CD4+ T cells, resulting in inhibited growth of transplanted ICB-resistant tumours. Furthermore, ICB treatment of castration-resistant prostate cancer (CRPC) patients results in re-activation of ACK1/pY18-CSK signalling, confirming the involvement of this pathway in ICB insensitivity. An ACK1 small-molecule inhibitor, (R)-9b, recapitulates inhibition of ICB-resistant tumours, which provides evidence for ACK1 enzymatic activity playing a pivotal role in generating ICB resistance. Overall, our study identifies an important mechanism of ICB resistance and holds potential for expanding the scope of ICB therapy to tumours that are currently unresponsive.

In vitro interaction of caspofungin and immunosuppressives against agents of mucormycosis.

OBJECTIVES: Mucormycosis is a rare but refractory mycosis with high mortality. Few therapeutic options are available and novel strategies are needed. Calcineurin inhibitors are known to have antifungal activity, including synergy with various antifungals. We examined the interaction of caspofungin with calcineurin inhibitors and sirolimus against Glomeromycetes. METHODS: Twenty-six strains of Glomeromycetes representing seven species (Rhizopus arrhizus, Rhizopus microsporus, Mucor sp., Rhizomucor pusillus, Cunninghamella berthollettiae, Mycocladus corymbifera and Apophysomyces elegans) were studied. Antifungal susceptibility testing was performed according to CLSI M38-A2, modified for chequerboard dilution testing using the minimum effective concentration (MEC) endpoint for caspofungin and calcineurin inhibitors/sirolimus. Synergy was defined as a fractional inhibitory concentration index ≤0.5, indifference >0.5 to ≤4.0 and antagonism >4.0. RESULTS: Caspofungin had no intrinsic activity against Glomeromycetes (MEC >8 mg/L). The combination of caspofungin with calcineurin inhibitors and sirolimus showed synergy in seven isolates. In the presence of calcineurin inhibitors and sirolimus, the MEC of caspofungin was significantly lowered (>4-fold) in 24 and 7 isolates, respectively. All species showed lower MECs of caspofungin with calcineurin inhibitors and only R. arrhizus, Mucor sp. and R. pusillus showed lower MECs with sirolimus. No antagonism was observed. CONCLUSIONS: Calcineurin inhibitors and sirolimus significantly lowered MECs of caspofungin for Glomeromycetes, with occasional synergy observed. The clinical significance of this should be further investigated.

Smart About Meds (SAM): a pilot randomized controlled trial of a mobile application to improve medication adherence following hospital discharge.

OBJECTIVE: The objectives of this pilot study were (1) to assess the feasibility of a larger evaluation of Smart About Meds (SAM), a patient-centered medication management mobile application, and (2) to evaluate SAM's potential to improve outcomes of interest, including adherence to medication changes made at hospital discharge and the occurrence of adverse events. MATERIALS AND METHODS: We conducted a pilot randomized controlled trial among patients discharged from internal medicine units of an academic health center between June 2019 and March 2020. Block randomization was used to randomize patients to intervention (received access to SAM at discharge) or control (received usual care). Patients were followed for 30 days post-discharge, during which app use was recorded. Pharmacy claims data were used to measure adherence to medication changes made at discharge, and physician billing data were used to identify emergency department visits and hospital readmissions during follow-up. RESULTS: Forty-nine patients were eligible for inclusion in the study at hospital discharge (23 intervention, 26 control). In the 30 days of post-discharge, 15 (65.2%) intervention patients used the SAM app. During this period, intervention patients adhered to a larger proportion of medication changes (83.7%) than control patients (77.8%), including newly prescribed medications (72.7% vs 61.7%) and dose changes (90.9% vs 81.8%). A smaller proportion of intervention patients (8.7%) were readmitted to hospital during follow-up than control patients (15.4%). CONCLUSION: The high uptake of SAM among intervention patients supports the feasibility of a larger trial. Results also suggest that SAM has the potential to enhance adherence to medication changes and reduce the risk of downstream adverse events. This hypothesis needs to be tested in a larger trial. TRIAL REGISTRATION: Clinicaltrials.gov, registration number NCT04676165.

Use of viral DNA surrogate markers to study routes of transmission of healthcare-associated pathogens.

BACKGROUND: The hands of healthcare personnel are the most important source for transmission of healthcare-associated pathogens. The role of contaminated fomites such as portable equipment, stethoscopes, and clothing of personnel in pathogen transmission is unclear. OBJECTIVE: To study routes of transmission of cauliflower mosaic virus DNA markers from 31 source patients and from environmental surfaces in their rooms. DESIGN: A 3-month observational cohort study. SETTING: A Veterans' Affairs hospital. METHODS: After providing care for source patients, healthcare personnel were observed during interactions with subsequent patients. Putative routes of transmission were identified based on recovery of DNA markers from sites of contact with the patient or environment. To assess plausibility of fomite-mediated transmission, we assessed the frequency of transfer of methicillin-resistant Staphylococcus aureus (MRSA) from the skin of 25 colonized patients via gloved hands versus fomites. RESULTS: Of 145 interactions involving contact with patients and/or the environment, 41 (28.3%) resulted in transfer of 1 or both DNA markers to the patient and/or the environment. The DNA marker applied to patients' skin and clothing was transferred most frequently by stethoscopes, hands, and portable equipment, whereas the marker applied to environmental surfaces was transferred only by hands and clothing. The percentages of MRSA transfer from the skin of colonized patients via gloved hands, stethoscope diaphragms, and clothing were 52%, 40%, and 48%, respectively. CONCLUSIONS: Fomites such as stethoscopes, clothing, and portable equipment may be underappreciated sources of pathogen transmission. Simple interventions such as decontamination of fomites between patients could reduce the risk for transmission.

Smart about medications (SAM): a digital solution to enhance medication management following hospital discharge.

OBJECTIVE: To outline the development of a software solution to improve medication management after hospital discharge, including its design, data sources, intrinsic features, and to evaluate the usability and the perception of use by end-users. MATERIALS AND METHODS: Patients were directly involved in the development using a User Center Design (UCD) approach. We conducted usability interviews prior to hospital discharge, before a user started using the application. A technology acceptance questionnaire was administered to evaluate user self-perception after 2 weeks of use. RESULTS: The following features were developed; pill identification, patient-friendly drug information leaflet, side effect checker, and interaction checker, adherence monitoring and alerts, weekly medication schedule, daily pill reminders, messaging service, and patient medication reviews. The usability interviews show a 98.3% total success rate for all features, severity (on a scale of 1-4) 1.4 (SD 0.79). Regarding the self-perception of use (1-7 agreement scale) the 3 highest-rated domains were: (1) perceived ease of use 5.65 (SD 2.02), (2) output quality 5.44 (SD 1.65), and (3) perceived usefulness 5.29 (SD 2.11). DISCUSSION: Many medication management apps solutions have been created and most of them have not been properly evaluated. SAM (Smart About Medications) includes the user perspective, integration between a province drug database and the pharmacist workflow in real time. Its features are not limited to maintaining a medication list through manual entry. CONCLUSION: We can conclude after evaluation that the application is usable and has been self-perceived as easy to use by end-users. Future studies are required to assess the health benefits associated with its use.