Max 3-4 pages, do not skip each question, each bullet !!
Please obtain from the web the 2010 paper by Nomura et al. on the discovery of canagliflozin.
· The title is: “Discovery of Canagliflozin, a Novel C-Glucoside with Thiophene Ring, as Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes Mellitus”.
· Also download the Supplemental Information
You may need to get additional information from Google, Wikipedia, or PubMed
Prepare a short summary of the properties of canagliflozin:
· Compound number on the paper, MW, and structure
· Originator and marketing companies (Wiki)
· Explain (one bullet) how the in vitro assays at SGLT-1 and SGLT-2 were performed
· Potency and selectivity at the relevant transporters in vitro
· Relevant PK parameters
· Pharmacodynamic effects in mice (do not forget to indicate doses and route of administration)
· Explain why the authors used “KK mice” (one bullet)
· Summary evaluation of the compound and its status in 2010
Please retrieve the 2014 paper by Mamidi et al. on the metabolism of canagliflozin.
Prepare a short summary:
· Title, authors, company, and citation (can copy/paste from pdf)
· Proposed in vivo metabolic pathways for canagliflozin in mice, rats, dogs, and humans
· Indicate on the above scheme the metabolites find in humans
· Add to the above scheme the CYPs and UGTs responsible for each metabolite found in humans (Hint: read the Discussion)
· Graph of PK of canagliflozin and metabolites in humans
· Which is the primary biotransformation pathway of canagliflozin in humans?
· What are the main differences in metabolism and excretion between animals and humans?
· Are the main metabolites in humans biologically active?
· Why wasn’t it necessary to test the non-clinical safety of the main human metabolites?
Please retrieve the 2013 paper by F. J. Lavalle-González et al. on a clinical trial with canagliflozin in T2D
Prepare and describing details and results of the trial as suggested below.
This should be very easy for the students by now!
· Copy/paste the title portion of the paper with title, authors, citation, and also the addresses of all the authors
· We want to know who they are and where they work
· Go to ClinicalTrials.gov and find the trial using its NCT number. Navigate to the “Tabular View” tab, which is easier to read. On your slide provide the following information (Try to copy/paste as much as possible):
· NCT number
· Brief Title
· Official Title
· Responsible Party
· Study Sponsor
· Study Director