Adiponectin Secretion Enhancer Synthetic Organic Drug Discovery and Development

DESCRIPTION provided by applicant DiscoveryBioMed Inc DBM completed recently Phase I SBIR funded goals milestones specific experimental aims and efforts to screen synthetic organic small molecules on immortalized and primary differentiated human adipocyte platforms and to validate the high throughput screening HTS based Drug Discovery output with a Critical Path of bioassays detecting secretion of endogenously produced species of the peptide adipokine adiponectin This design yielded hit to lead chemical classes that are potent and effective in potentiating the endogenous production and secretion of human low medium and higher molecular weight HMW forms of adiponectin a beneficial adipokine for normal metabolism and insulin target tissue protection that is lost during the emergence and progression of type diabetes mellitus T DM and obesity Accordingly up regulating endogenous adiponectin expression and secretion within the human body has been proposed as a therapeutic strategy for diabetes and obesity especially to block secondary injury of other fragile human tissues The ultimate goal of this proposed Phase II work is to select profile focus and optimize through medicinal chemistry DBMandapos s lead and back up lead chemical classes of higher molecular weight adiponectin secretagogue ligands HMW ASLs to realize potent and effective lead clinical candidate drugs that will block secondary complications of T DM obesity and related metabolic diseases in the nearer term and attenuate T DM and obesity in general as a secondary endeavor The key ingredient in this program is the use of biologically and disease relevant human cellular platforms primary differentiated human adipocytes to profile hit to lead new chemical entities This core principle reflects DBMandapos s unique angle approach and offering to the Drug Discovery space andapos Humanized Drug Discoveryandapos It is DBMandapos s core belief that a successful de novo drug discovery program must utilize a disease relevant human cell platform and a disease relevant targeted and phenotypic endpoint i e human adipocytes secreting human adiponectin The rationale and potential market impact of this DBM Metabolic Diseases Drug Discovery and Development program are straightforward and enormous Obesity and obesity related diseases including T DM atherosclerosis cardiovascular disease fatty liver disease and diabetic hyperglycemic injury of the eye heart vasculature kidney and peripheral nerves have reached epidemic proportions in the US and the developed world and exact huge morbidity and cost burdens on global society An immense unmet clinical need exists for new therapeutic drugs to combat these diseases especially in Alabama where our company resides in the heart of andquot the Southeastern Diabetes Belt andquot This market is estimated to be $ trillion by Yet metabolic diseases drug discovery and development is at a near standstill Hence there is an andapos open window of opportunityandapos to re kindle the metabolic disease drug discovery effort Our NIDDK Phase I SBIR award has allowed DBM to launch this critical program Phase II project milestones are proposed as follows and will continue the momentum of this SBIR driven program Current transitional scientific activity seeks to evaluate and select multiple lead and back up lead chemical series that are potent and effective HMW ASLs at the onset of the program Chemoinformatics analyses progressed out of validated hit chemical classes and subsequent medicinal chemistry analyses have selected out of hit to lead chemical classes for entry into Phase SBIR driven work A continuing milestone seeks to profile andapos best in classandapos compounds from the hit to lead HMW ASL classes in primary human adipocyte culture platforms from normal T DM and overweight obese donors and from both subcutaneous and visceral adipose tissue sources Subsequent milestones involve collaborative work with CROs and academic collaborators consultants in in vitro and in vivo ADME PK and MTD safety and toxicity studies in mice in vivo proof of concept studies in animal models of T DM obesity and related disorders medicinal chemistry design optimization and profiling of analogs from ultimately lead and back up lead drug classes to improve potency and or efficacy of chemical series and re performance of in vivo proof of concept studies in metabolic diseases animal models This proposed Phase II program scripts full IND enabling studies so as to select a lead clinical candidate drug and seek partnership with an interested BioPharma PUBLIC HEALTH RELEVANCE Increasing adoption of the andquot western lifestyleandquot i e high fat high calorie diet and sedentary lifestyle has led to an explosion in global diabetes and obesity rates
Health care costs due to obesity itself and obesity linked non communicable diseases such as type diabetes mellitus stroke heart disease as well as high blood sugar and high blood fat driven injury of tissues and organs such as the eye kidney vasculature and liver are expected to reach a staggering cost of $ trillion over the next years DiscoveryBioMed Inc DBM seeks to combat this alarming trend by discovering completely novel synthetic organic small molecule compounds to profile and progress as lead clinical candidate drugs for management treatment and attenuation of secondary tissue injury caused by obesity and diabetes and ultimately treatment of type diabetes obesity and related metabolic diseases in general For this program we seek to discover and develop drugs that stimulate the endogenous production and secretion of a beneficial adipokine adiponectin This protective adipokine secreted by human fat cells within adipose tissue is lost during the progression of diabetes and obesity Adiponectin is a complex secreted peptide that cannot be synthesized as a biologic injectable preparation like injected insulin Our company envisions an oral medicine that is a novel potent and effective andapos first in classandapos drug that is a andapos game changerandapos to capture a significant percentage o a projected $ trillion market as of For DBM this program has a local and essential mission given the alarming obesity and diabetes trends in Alabama and the greater Southeast region known as the andquot diabetes belt andquot