
Development of Novel Melanocortin-4 Receptor Peptide Agonists for the Treatment ofMC4R HaploinsufficiencyAward last edited on: 2/15/2024
Sponsored Program
STTRAwarding Agency
NIH : NIDDKTotal Award Amount
$1,914,458Award Phase
2Solicitation Topic Code
300Principal Investigator
Tomui K SawyerCompany Information
Phase I
Contract Number: 1R41DK127817-01Start Date: 9/11/2020 Completed: 8/31/2021
Phase I year
2020Phase I Amount
$244,905Public Health Relevance Statement:
Rates of obesity have steadily increased in the United States, with approximately 50 percent of Americans projected to be classified as obese by 2030. Although behavioral (dieting and exercise), pharmacological, and surgical approaches exist for weight loss, many individuals who lose weight are unable to sustain this weight loss due to compensatory behavioral, autonomic, and neuroendocrine pathways promoting rebound weight gain. The product of this Phase I STTR will be patentable MC3R antagonist lead development candidates that may be used as novel agents for the maintenance of weight loss.
Project Terms:
alpha-Melanocyte stimulating hormone; Melanocortin-1; alpha-MSH; alpha-Melanotropin; a-MSH; a-Melanocyte stimulating hormone; Biological Assay; Assay; Bioassay; Biologic Assays; Brain; Brain Nervous System; Encephalon; Cells; Cell Body; Clinical Trials; Diet; dietary; Disease; Disorder; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Eating; Food Intake; Exercise; Fasting; fasted; fasts; Human; Modern Man; Hybrids; In Vitro; Lead; Pb element; heavy metal Pb; heavy metal lead; Ligands; Neurons; Nerve Cells; Nerve Unit; Neural Cell; Neurocyte; neuronal; Neurosecretory Systems; Neuroendocrine; Neuroendocrine System; Obesity; adiposity; corpulence; corpulency; corpulentia; obese; obese people; obese person; obese population; Patients; Peptides; Periodicity; Cyclicity; Rhythmicity; Pharmacology; Publishing; Risk Factors; Specificity; Structure-Activity Relationship; chemical structure function; structure function relationship; Synapses; Synaptic; synapse; Syndrome; Testing; United States; Weight Gain; Weight Increase; body weight gain; body weight increase; wt gain; Body Weight decreased; Weight Loss; Weight Reduction; body weight loss; wt-loss; Weight; Mediating; G(s), alpha Subunit; G(s), a Subunit; G(s)alpha; G(s)a; GTP-Binding Protein a Subunits, Gs; Gs alpha Family G-Protein; Gsa; Gas; Regulatory Ns Protein; Stimulatory Gs G-Protein; alpha Subunit Stimulatory GTP-Binding Protein; alpha-Gs; a-Gs; GTP-Binding Protein alpha Subunits, Gs; improved; Peripheral; Penetration; Phase; Series; Peptide Receptor; Chemicals; insight; Individual; analog; Funding; Agonist; MC3 Receptor; Receptor, Melanocortin, Type 3; Melanocortin 3 Receptor; melanocortin receptor; Therapeutic; tool; Complex; disease severity; Severity of illness; SHU9119; SHU 9119; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; American; peptide analog; Receptor Protein; receptor; success; Arg-Arg; arginyl-L-arginine; arginylarginine; MC4 Receptor; Receptor, Melanocortin, Type 4; Melanocortin 4 Receptor; Structure; novel; Modality; Position; Positioning Attribute; Bardet Biedel syndrome; Bardet-Biedl Syndrome; Property; response; caloric restricted; calorically restricted; calorie restricted; calorie restriction; Caloric Restriction; Molecular Interaction; Binding; preventing; prevent; Animal Testing; Data; in vivo; STTR; Small Business Technology Transfer Research; Process; Modification; developmental; Development; Behavioral; pathway; Pathway interactions; weight maintenance; obesity treatment; feeding; Leptin deficiency; designing; design; diet and exercise; new approaches; novel approaches; novel strategy; novel strategies; Coupling; comparative; lead optimization; lead candidate; obesity development; COVID19; corona virus disease 2019; coronavirus disease 2019; COVID-19; Scenesse; afamelanotide
Phase II
Contract Number: 2R42DK127817-02Start Date: 9/11/2020 Completed: 8/31/2024
Phase II year
2022(last award dollars: 2023)
Phase II Amount
$1,669,553Public Health Relevance Statement:
Rates of obesity have steadily increased in the United States, with approximately 50 percent of Americans projected to be classified as obese by 2030. While a recently approved drug Imcivree is effective for rare forms of syndromic obesity, it lacks efficacy for the most common obesity syndrome, haploinsufficiency of the melanocortin-4 receptor (MC4R), effecting more than as 1 in 1000 individuals. The product of this Phase II STTR will be MC4R agonist therapeutics that may be used as novel agents for the treatment of human MC4R haploinsufficiency.
Project Terms:
Biological Assay; Assay; Bioassay; Biologic Assays; Brain; Brain Nervous System; Encephalon; Clinical Research; Clinical Study; Drug Evaluation; Drug Evaluation Studies; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Eating; Food Intake; Exhibits; Family; Half-Life; Human; Modern Man; In Vitro; melanocyte; Methods; Obese Mice; ob/ob mouse; Microspheres; Microbeads; Mus; Mice; Mice Mammals; Murine; Nerve Cells; Nerve Unit; Neural Cell; Neurocyte; neuronal; Neurons; adiposity; corpulence; Obesity; Patients; Peptides; Pharmacokinetics; Drug Kinetics; Wistar Rats; Safety; Mass Photometry/Spectrum Analysis; Mass Spectrometry; Mass Spectroscopy; Mass Spectrum; Mass Spectrum Analyses; Mass Spectrum Analysis; chemical structure function; structure function relationship; Structure-Activity Relationship; Syndrome; Testing; Toxicology; United States; Body Weight decreased; Weight Loss; Weight Reduction; body weight loss; wt-loss; Work; Roentgen Rays; X-Radiation; X-Ray Radiation; X-ray; Xray; Injectable; Hyperpigmentation; Hypermelanoses; Hypermelanosis; base; improved; Acute; Chronic; Phase; Medical; Peptide Receptor; Chemicals; Dermal; Blood Serum; Serum; Individual; Data Bases; data base; Databases; analog; Agonist; MC3 Receptor; Receptor, Melanocortin, Type 3; Melanocortin 3 Receptor; melanocortin receptor; Abnormal Assessment of Metabolism; Metabolic Studies; Metabolism Studies; metabolic abnormality assessment; Therapeutic; Contracting Opportunities; Contracts; Rivers; HuB219; LEP-R; LEPR Protein; OB Receptor; OB-R; leptin-binding protein; leptin receptor; subdermal; subcutaneous; Techniques; American; Receptor Protein; receptor; Cryo-electron Microscopy; Electron Cryomicroscopy; cryo-EM; cryoEM; Cryoelectron Microscopy; Toxicities; Toxic effect; MC4 Receptor; Receptor, Melanocortin, Type 4; Melanocortin 4 Receptor; Structure; novel; MC1 Receptor; Melanocyte Melanocortin Receptor; Melanocortin 1 Receptor; Pharmacodynamics; Cardiac Toxicity; Cardiotoxic; Cardiotoxicity; Patient Compliance; patient adherence; patient cooperation; therapy compliance; therapy cooperation; treatment compliance; compliance behavior; Dose; Data; in vivo; Small Business Technology Transfer Research; STTR; Development; developmental; safety study; Pathway interactions; pathway; cost; design; designing; Prevalence; mouse model; murine model; commercialization; screening; Formulation; peptide drug; Peptide-based drug; therapeutic peptide; therapeutic candidate; human model; model of human; in vivo evaluation; in vivo testing; side effect; dietary; antagonist