PCI 27483 / AbbVie - LARVOL DELTA

Polypharmacology of carbonic anhydrase inhibitors and activators. (PubMed, Expert Opin Pharmacother) - "Several antiepileptics (topiramate, zonisamide, lacosamide, levetiracetam), some atypical antipsychotics (sulpiride, veralipride), celecoxib, polmacoxib, pazopanib, the antiulcer agent famotidine and compounds in clinical trials (epacadostat and PCI-27483) as antitumor agents significantly inhibit several CA isoforms of the 15 human ones, apart their action on several other targets...Polypharmacology involving CA inhibitors/CAAs are understood from the chemical, structural and pharmacological viewpoints. The many other drug targets with which these modulators of activity interact allow for de novo design of such agents for the management of multifactorial conditions in need of innovative drugs."

Journal • Review • CNS Disorders • Epilepsy • Genetic Disorders • Glaucoma • Obesity • Oncology • Ophthalmology

Exploring the Polypharmacological Potential of PCI-27483: A Selective Inhibitor of Carbonic Anhydrases IX and XII. (PubMed, ACS Med Chem Lett) - "This study investigates the inhibitory activity of PCI-27483 against the complete panel of active hCAs, highlighting its polypharmacological potential in cancer treatment. X-ray crystallography and molecular docking studies elucidated the structural features underlying its selective inhibitory activity toward hCA IX and XII, offering insights into its dual-targeting pathway."

Journal • Oncology

Suite of TMPRSS2 Assays for Screening Drug Repurposing Candidates as Potential Treatments of COVID-19. (PubMed, ACS Infect Dis) - "Of the six molecules advanced for further studies, two are approved drugs in Japan (camostat and nafamostat), two have entered clinical trials (PCI-27483 and otamixaban), while the other two molecules are peptidomimetic inhibitors of TMPRSS2 taken from the literature that have not advanced into clinical trials (compounds 92 and 114). This work demonstrates a suite of assays for the discovery and development of new inhibitors of TMPRSS2."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Structure-based phylogeny identifies Avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice. (PubMed, J Clin Invest) - "Several candidate compounds, Avoralstat, PCI-27483, Antipain, and Soybean-Trypsin-Inhibitor, inhibited TMPRSS2 in biochemical and cell infection assays. Avoralstat, a clinically tested Kallikrein-related B1 inhibitor, inhibited SARS-CoV-2 entry and replication in human airway epithelial cells. In an in vivo proof of principle, Avoralstat significantly reduced lung tissue titers and mitigated weight-loss when administered prophylactically to SARS-CoV-2 susceptible mice indicating its potential to be repositioned for COVID-19 prophylaxis in humans."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study of safety and tolerability of PCI-27483 in patients with pancreatic cancer patients receiving treatment with gemcitabine (clinicaltrials.gov) - P2, N=40; Recruiting -> Active, not recruiting

Enrollment closed • Pancreatic Cancer

A Phase 2 Study of PCI-27483, a Factor VIIa Inhibitor in Combination with Gemcitabine for Advanced Pancreatic Cancer. (PubMed, Oncology) - "Targeted inhibition of the coagulation cascade was achieved by administering PCI-27483. PCI-27483-gemcitabine was well tolerated, but superiority to single agent gemcitabine was not demonstrated."

Combination therapy • Journal • P1 data • P2 data