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Article
Open AccessDe novo generation of multi-target compounds using deep generative chemistry
Polypharmacology drugs—compounds that inhibit multiple proteins—have many applications but are difficult to design. To address this challenge we have developed POLYGON, an approach to polypharmacology based on...
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Protocol
Software and Databases for Protein–Protein Docking
Protein–protein interactions (PPIs) provide valuable insights for understanding the principles of biological systems and for elucidating causes of incurable diseases. One of the techniques used for computation...
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Article
Open AccessAnti-TNF-α therapy induced psoriasis in rheumatoid arthritis patients according to FDA postmarketing surveillance data
Rheumatoid arthritis, RA, is a chronic autoimmune disease characterized by joint pain, tenderness, swelling, and stiffness. This disease affects nearly 1% of the world population. RA predominates in females an...
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Article
Open AccessPostmarketing safety surveillance data reveals protective effects of botulinum toxin injections against incident anxiety
Randomized controlled trials (RCTs) have shown an antidepressant effect of glabellar botulinum toxin (BoNT) injections. In the FDA Adverse Event Reporting System (FAERS) database, BoNT injection is associated ...
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Article
Open AccessCommon osteoporosis drug associated with increased rates of depression and anxiety
Osteoporosis affects over 10 million Americans over 50. Bisphosphonate therapy, mainly alendronate, is amongst the most prescribed treatments for the disease. The use of alendronate and other bisphosphonates h...
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Article
Open AccessMyocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data
Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient’s own immune system to target...
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Article
Retraction Note: Orphan receptor ligand discovery by pickpocketing pharmacological neighbors
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41589-021-00746-1.
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Article
Open AccessConcomitant drugs associated with increased mortality for MDMA users reported in a drug safety surveillance database
3,4-Methylenedioxymethamphetamine (MDMA) is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of post-traumatic stress disorder (PTSD). If MDMA is FDA-approved it will be im...
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Article
Open AccessElucidation of transient protein-protein interactions within carrier protein-dependent biosynthesis
Fatty acid biosynthesis (FAB) is an essential and highly conserved metabolic pathway. In bacteria, this process is mediated by an elaborate network of protein•protein interactions (PPIs) involving a small, dyn...
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Article
Open AccessCardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports
Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization’s List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus...
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Article
Open AccessPostmarketing safety surveillance data reveals antidepressant effects of botulinum toxin across various indications and injection sites
The World Health Organization estimates the number of people suffering from depression to be over 264 million. Current monoamine transmission modulating therapeutics, even with proper adherence and acceptable ...
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Article
Druggable exosites of the human kino-pocketome
Small molecules binding at any of the multiple regulatory sites on the molecular surface of a protein kinase may stabilize or disrupt the corresponding interaction, leading to consequent modulation of the kina...
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Article
Macrocycle modeling in ICM: benchmarking and evaluation in D3R Grand Challenge 4
Macrocycles represent a potentially vast extension of drug chemical space still largely untapped by synthetic compounds. Sampling of flexible rings is incorporated in the ICM-dock protocol. We tested the abili...
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Article
Open AccessProton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory
Proton-pump inhibitors, PPIs, are considered effective therapy for stomach acid suppression due to their irreversible inhibition of the hydrogen/potassium pump in the gastric parietal cells. They are widely pr...
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Article
Open AccessDiscovery of holoenzyme-disrupting chemicals as substrate-selective CK2 inhibitors
CK2 is a constitutively active protein kinase overexpressed in numerous malignancies. Interaction between CK2α and CK2β subunits is essential for substrate selectivity. The CK2α/CK2β interface has been previou...
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Article
Open AccessMulti-center screening of the Pathogen Box collection for schistosomiasis drug discovery
Over the past five years, as a public service to encourage and accelerate drug discovery for diseases of poverty, the Medicines for Malaria Venture (MMV) has released box sets of 400 compounds named the Malari...
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Article
Open AccessRetrospective analysis reveals significant association of hypoglycemia with tramadol and methadone in contrast to other opioids
Tramadol is one of the most commonly used analgesics worldwide, classified as having a low abuse potential by U.S. Drug Enforcement Agency, and often recommended in pain management guidelines. Its pain-relievi...
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Article
Population Scale Retrospective Analysis Reveals Potential Risk of Cholestasis in Pregnant Women Taking Omeprazole, Lansoprazole, and Amoxicillin
In nearly 50% of patients with drug-induced liver injury, the bile flow is impaired known as cholestasis. Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease that happens in pregnancy....
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Article
Open AccessAnalysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis
Proton pump inhibitors, PPIs, are widely prescribed and sold globally. Although initially intended for time-limited treatment of acute disorders, such as gastric ulcers and esophagitis, PPIs are now commonly u...
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Article
Hybrid receptor structure/ligand-based docking and activity prediction in ICM: development and evaluation in D3R Grand Challenge 3
In context of D3R Grand Challenge 3 we have investigated several ligand activity prediction protocols that combined elements of a physics-based energy function (ICM VLS score) and the knowledge-based Atomic Pr...
