Malaria Libre 3 - project meeting 11 - September 2020

PowerPoint Presentation Malaria Libre 3rd project meeting 11th September 2020 • Please keep cameras and microphones switched off • Switch on the microphone during your turn for discussion • Type your request for questions/ discussion point in the chat box 2 Agenda • Introductory session – if new members join • Status of action items from last meeting • Project update • Discussion – Medicinal Chemi. [...] Venkat – aryl piperazine O O O * * N N O N N H NH Cl N O O N N N N N Cl N N N CN H H Only for SAR Cl O Also CN N N explore N N N N N N N H for LHS N N O Cl N N N N CN N N N N N N Cl H * CN Cl N N N Cl H N N Cl N N N N * N O N N N X N Proposal by R Venkat – aryl imidazole N O O N NN NH NH X NH X N X X X X For LHS XX = CH , O, NMe 2 X = CH , O, NMe 2 N N H N NH NH H X X O O X O N X X X X X X H N X N. [...] Open Science1 Open Innovation1 …..deposition of …..project data in the public partners sharing domain all information Open Access1,2 Open Source1,3 …..free access to …..shared data data and and open materials participation 1. [...] schizont) Based on microscopy In vitro PRR (Log10), onset of action (h) and Hill Slope Novel based on resistance panel or strategic Mechanism of action imperative if known Pb/ Pf liver schizont EC50 EC50<100nM for causal TCP4 Pc/ Pv hypnozoite EC50 EC50<1000nM for TCP3 Pf NF54 Gametocyte stage I/ III EC50 Measured Pf NF54 Gametocyte stage V EC50 EC50<100nM for TCP5 Pf Male gamete formation assay (. [...] (dose), Tmax, Cmax, AUC, F%, t1/2 acceptable vehicle TCP1 Dose to clear 9 / 12 Logs parasites from single/ three qd dose(s) For TCP1 TCP4 Dose to give t>prophylactic concentration for 7 days from single dose For TCP4 Predicted adult human t1/2, Cl and V hours, mL/min/Kg, L/Kg hERG IC50 uM (manual patch clamp) >1uM; some potent examples >10uM 31.