11.03.2021 | Webinar: automated patch clamp webinar high throughput functional evaluation of melanocortin and a CiPA based evaluation of proarrhythmic risk
Date: March 11. 2021
Ciria Hernandez, MD, Ph.D
(Assistant Research Scientist - University of Michigan Life Sciences Institute)
(Principal Scientist - Charles River Laboratories)
Presenter: Ciria Hernandez, MD, Ph.D
High-Throughput Functional Evaluation of Melanocortin Compounds at the MC4R-Kir7.1 Complex: Biased Signaling at the Melanocortin 4 Receptor
Melanocortin 4 receptors (MC4R) are G-protein coupled receptors (GPCR) that mediate a variety of physiological processes critical for energy homeostasis. Loss-of-function MC4R mutations are linked to early-onset syndromic obesity. MC4R is the first GPCR reported to functionally directly interact with the inward rectifier potassium channel Kir7.1. In the paraventricular nucleus of the hypothalamus, MC4R activation leads to Kir7.1 closure causing neuronal depolarization and satiety, whereas its inhibition promotes channel opening leading to membrane hyperpolarization and hunger. The discovery of a G-protein independent pathway for MC4R signaling through Kir7.1 opened new venues for the exploration of new signaling pathways by GPCRs."
Presenter: Yuri Kuryshev
CiPA Based Evaluation of Proarrhythmic Risk Using the SyncroPatch 384PE
Cardiac arrhythmias are a limiting factor for development of new drugs in any therapeutic area. Proarrhythmic risk prediction modeling is a contemporary approach for cardiac safety and the modeling requires reliable experimental data for drug effects on four major cardiac ion channel currents – hERG, Cav1.2 (peak and late) and Nav1.5 (late). We have validated these channel assays on SyncroPatch 384PE platform and applied them to evaluation several drugs with questionable proarrhythmic safety.