COLLABORATIONS PHARMACEUTICALS INC — Department of Health and Human Services STTR Phase I: NIAID

Description

DESCRIPTION provided by applicant Tuberculosis TB is due to infection with the pathogen Mycobacterium tuberculosis Mtb This disease represents a global health pandemic as based on WHO statistics it claims the lives of approximately million people per year while infecting nearly million New drugs are urgently needed with novel mechanisms of action that treat this disease while also addressing an important need to reduce the lengthy course of treatment that is at best months in duration We have a primary goal of discovering novel classes of antibacterials E nitrofuran yl methylene hydrazinyl N N diphenyl triazine diamine JSF was rediscovered by us using Bayesian machine learning models in It represents a class of antitubercular agents reported only once in While JSF did not exhibit in vivo efficacy in an acute model in our hands a close analog E N N diisopropyl nitrofuran yl methylene hydrazinyl triazine diamine JSF was reported in to exhibit in vivo activity Our preliminary data on solubility in PBS mouse liver microsomal stability Caco cell permeability and mouse snapshot pharmacokinetic PK profiles demonstrate that the diaminotriazine class of antituberculars holds significant promise for seeding a novel therapeutic We aim to further improve upon the in vitro efficacy in vitro Absorption Distribution Metabolism and Excretion ADME and in vivo pharmacokinetic PK profiles of these early compounds The Specific Aims of this proposed research are Utilize medicinal chemistry and predictive ADME models to optimize the initial triazine hit family as antitubercular agents Apply transcriptional profiling nd resistant mutant whole genome sequencing methods to identify potential drug targets and mechanism of action of the triazine antitubercular class Phase I would therefore seek to deliver an in vivo active small molecule triazine with information as to potential target s through complimentary methods A Phase II program would leverage this information to further optimize this series towards a preclinical candidate of significant interest to foundations and or biotech pharmaceutical companies PUBLIC HEALTH RELEVANCE Tuberculosis represents a global health pandemic which claims the lives of approximately million people per year Starting from a series of triazines active compounds we will optimize ADME properties to afford a novel in vivo active lead compound by combining our unique expertise in medicinal chemistry and predictive ADME models We will also probe the potential target s of the triazine series We will further leverage the exceptional facilities at Rutgers to ultimately lead to a clinical candidate by the end of phas II