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Principal Investigator: Huan Xie
Organization: TEXAS SOUTHERN UNIVERSITY
Fiscal Year: 2023
Award: $170,518
Funding agency: National Institute on Minority Health and Health Disparities
PROJECT SUMMARY
Prostate cancer (PCa) is the second leading cause of cancer death in the United States among men and it is
more common in African American males. Despite initial good responses to androgen deprivation or anti-
androgen drugs, tumors invariably recur and develop into lethal castration resistant prostate cancer (CRPC).
Currently, the available therapeutic options for CRPC, including the gold standard chemotherapy docetaxel, have
only met with limited success. The 52 kDa FK506 binding protein (FKBP52) is a promising strategy for novel
targeted therapeutic development. MJC13 and GMC1, two first-in-class drugs that specifically inhibit FKBP52-
mediated potentiation of AR signaling, have been discovered by Dr. Cox at University of Texas at El Paso and
further developed by Dr. Xie at Texas Southern University. The exciting anti-tumor efficacy observed in CRPC
xenograft animal models encourage us to further develop novel targeted nano-drug delivery systems (NDDS)
that specifically deliver MJC13 and GMC1 to the tumor site then steadily release the drug to facilitate synergistic
effect with docetaxel to treat CRPC.
Our aims are to develop folic acid (FA)-conjugated NDDS of MJC13 and GMC1 for specific tumor targeting, high
efficacy and low off-target adverse reactions; to perform comprehensive in vivo pharmacokinetic and
pharmacodynamic evaluations on the optimal NDDS of MJC13 and GMC1; to investigate combination therapy
of MJC13 and GMC1 and docetaxel in comparison to the marketed anti-AR drug enzalutamide. We will use
various techniques, rats, tumor xenograft mouse models and genetically engineered mouse models to conduct
those experiments in collaboration with experts at TSU and other institutions.
This project will seek support and evaluation from the CBMHR Administrative Core, will heavily utilize the
Research Infrastructure Core to perform studies, and will disseminate the research findings from this project with
various TSU communities via support from our Community Engagement Core (CEC). It will further enhance
RCMI institutions’ prestige in the areas of biomedical and minority health research. The successful execution of
this research will result potential advanced treatment for CRPC patients.
Terms: <22RV1><Address><Adverse reactions><Affinity><African American><African American group><African American individual><African American people><African American population><African Americans><Afro American><Afroamerican><Agreement><Androgen Antagonists><Androgen Receptor><Androgenic Agents><Androgenic Compounds><Androgens><Animal Model><Animal Models and Related Studies><Anti-Androgen><Anti-Androgen Agents><Antiandrogen Agents><Antiandrogens><Antigen Targeting><Area><Award><Binding><Bioavailability><Biological Availability><CWR22Rv1><CaCo2><Caco-2 Cells><Cancer Cause><Cancer Etiology><Cancer Patient><Cell Culture Techniques><Cell model><Cellular model><Cessation of life><Characteristics><Chemosensitization><Chemosensitization/Potentiation><Clinical Data><Clinical Research><Clinical Study><Clinical Trials><Collaborations><Combined Modality Therapy><Common Rat Strains><Communities><Data><Death><Disease><Disorder><Dose><Drug Delivery><Drug Delivery Systems><Drug Receptors><Drug Targeting><Drug or chemical Tissue Distribution><Drugs><Endocrine Gland Secretion><Environment><Enzyme Gene><Enzymes><Evaluation><FK-506-Binding Protein><FK506 Binding Proteins><FK506 binding protein 59><FK506-binding protein 4><FKBP><FKBP Rotamase><FKBP4><FKBP52><FKBP59><FOLH><FOLH1><FOLH1 gene><Folate><Folate Hydrolase 1><Folic Acid><Food><Formulation><Fostering><Future><GCP2><GEM model><GEMM model><Gene Expression><Genetically Engineered Mouse><Glutamate Carboxypeptidase II><Goals><HSP 56><HSP56><Heterograft><Heterologous Transplantation><Hormones><Incidence><Institution><Intermediary Metabolism><Intestinal><Intestines><Intravenous><Investigational Drugs><Investigational New Drug Application><Investigational New Drugs><Legal patent><Liposomal><Liposomes><Magic><Malignant Tumor of the Prostate><Malignant neoplasm of prostate><Malignant prostatic tumor><Marketing><Mediating><Medical><Medication><Membrane><Metabolic Processes><Metabolism><Minority Health Research><Minority research><Modeling><Molecular Interaction><Monitor><Morphology><Multimodal Therapy><Multimodal Treatment><N-Acetylated Alpha-Linked Acidic Dipeptidase 1><NAALAD1><NAALADase I><New Drug Approvals><Outcome><PK/PD><PSM><PSMA><Particle Size><Patents><Pathway interactions><Patients><Perfusion><Pharmaceutic Preparations><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Physiologic Availability><Polymers><Potentiation><Primates><Primates Mammals><Prostate CA><Prostate Cancer><Prostate malignancy><Prostate-Specific Membrane Antigen><Prostatic Cancer><Pteroylglutamic Acid><Publications><Race><Races><Rat><Rats Mammals><Rattus><Reaction><Receptor Signaling><Recurrence><Recurrent><Regimen><Research><Research Infrastructure><Role><Scientific Publication><Series><Site><Solid><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Surface><Tacrolimus Binding Proteins><Taxotere><Techniques><Texas><Therapeutic><Therapeutic Androgen><Therapeutic Hormone><Tissue Distribution><Training><United States><Universities><Vitamin M><Xenograft><Xenograft Model><Xenograft procedure><Xenotransplantation><Xtandi><absorption><advanced prostate cancer><androgen inhibitor><anti-tumor effect><antitumor effect><bowel><castrate resistant PCa><castrate resistant prostate cancer><castration resistant CaP><castration resistant PCa><castration resistant prostate cancer><cell culture><cell cultures><chemotherapy><clinical applicability><clinical application><combination therapy><combined modality treatment><combined treatment><community engagement><deprivation><docetaxel><docetaxol><drug candidate><drug/agent><enzalutamide><experiment><experimental research><experimental study><experiments><fighting><first in man><first-in-human><genetically engineered mouse model><genetically engineered murine model><heat shock-binding immunophilin><heat-shock protein 56><in vivo><indexing><intravenous administration><lipid based nanoparticle><lipid nanoparticle><male><membrane structure><men><minority student><model of animal><mortality><mouse model><multi-modal therapy><multi-modal treatment><murine model><nanodrug><nanopharmaceutical><new approaches><new drug target><new drug treatments><new druggable target><new drugs><new pharmacological therapeutic><new pharmacotherapy target><new therapeutic target><new therapeutics><new therapy><new therapy target><next generation therapeutics><novel><novel approaches><novel drug target><novel drug treatments><novel druggable target><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel pharmacotherapy target><novel strategies><novel strategy><novel therapeutic target><novel therapeutics><novel therapy><novel therapy target><overexpress><overexpression><p59 heat shock-binding immunophilin><pathway><pharmaceutical><pharmacodynamic model><pharmacokinetics and pharmacodynamics><polymer><polymeric><pre-clinical study><preclinical study><prostate cancer cell><prostate cancer cell line><prostate tumor cell><racial><racial background><racial origin><research in minorities><research on minorities><research related to minorities><research with minorities><response><social role><standard care><standard treatment><statistical analysis><success><synergism><tacrolimus binding protein 4><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic agent development><therapeutic development><tumor><tumor growth><tumor xenograft><vitamin Bc><xeno-transplant><xeno-transplantation><xenograft transplant model><xenotransplant model><zeta potential>