Mays Oncology Intelligence

Research & Discovery

Center for Innovative Drug Discovery (CIDD) platforms, breakthrough research, and funding powering the Mays Cancer Center oncology pipeline.

Discovery Platforms

CIDD technology platforms enabling next-generation therapeutics

PROTAC / Targeted Protein Degrader Platform
Director: Dr. Daohong Zhou

Industry-leading platform for designing and optimizing proteolysis-targeting chimeras (PROTACs) that selectively degrade disease-causing proteins. Pioneered the use of VHL-recruiting PROTACs to achieve tissue-selective degradation, overcoming toxicity limitations of traditional inhibitors.

Capabilities

Rational PROTAC design with E3 ligase selectivity (VHL, CRBN, IAP)High-throughput ternary complex modeling and optimizationIn vivo PROTAC pharmacokinetics and pharmacodynamicsTissue-selective degradation through E3 ligase expression profiling

Key Achievements

  • - Invented DT2216 — first BCL-XL PROTAC, now in Phase 1/2 clinical trials
  • - Published landmark PROTAC papers in Nature Medicine (2019, 2020)
  • - CPRIT award ($11M) for PROTAC platform advancement
CRISPR Functional Genomics Screening Platform
Director: Dr. Stanton McHardy

Genome-wide CRISPR screening platform for identifying novel drug targets, understanding resistance mechanisms, and validating therapeutic vulnerabilities in cancer cells. Integrates with the degrader platform to nominate new PROTAC targets.

Capabilities

Genome-wide CRISPR knockout (CRISPRko) screensCRISPR activation (CRISPRa) and interference (CRISPRi) screensCombinatorial CRISPR screens for synthetic lethalityDrug resistance and sensitization screens

Key Achievements

  • - Identified novel BCL-XL resistance mechanisms informing DT2216 combinations
  • - Discovered synthetic lethal targets for PROTAC-based therapeutic strategies
  • - Published CRISPR screen data supporting multiple CIDD drug programs
Medicinal Chemistry & Drug Discovery Platform
Director: Dr. Stanton McHardy

Full-spectrum medicinal chemistry platform spanning hit identification through IND-enabling studies. Specializes in challenging chemical matter including PROTACs, molecular glues, and covalent inhibitors.

Capabilities

Structure-based drug design (SBDD) with in-house computational chemistryPROTAC and molecular glue medicinal chemistryFragment-based drug discovery (FBDD)ADMET optimization and pharmacokinetic profiling

Key Achievements

  • - Optimized DT2216 from hit to clinical candidate in 18 months
  • - Developed scalable synthetic routes for PROTAC drug substances
  • - Filed 12 patents on PROTAC and degrader compositions

Research Breakthroughs

Landmark discoveries from UT Health San Antonio researchers

Chemical Endocytic Mechanism — A New Paradigm for Cellular Uptake
Breakthrough

Dr. Hong-yu Li's laboratory discovered a previously unknown mechanism by which cells internalize extracellular molecules through a chemical endocytic process that is independent of classical receptor-mediated endocytosis, pinocytosis, and phagocytosis. This fundamentally new pathway is triggered by specific chemical motifs on molecules interacting with the cell membrane, inducing membrane invagination and vesicle formation without requiring surface receptor engagement.

Cell2025

Significance: Landmark fundamental biology discovery

Discoverer: Dr. Hong-yu Li — UT Health San Antonio CIDD

CPRIT Awards

Development of First-in-Class BCL-XL PROTAC Degrader (DT2216)

CPRIT Product Development award supporting the clinical development of DT2216 from IND-enabling studies through Phase 1 clinical trials. Funds CMC manufacturing, nonclinical toxicology, and clinical trial operations.

$11,000,0002020–2025active

PI: Dr. Daohong Zhou | DP200120

Center for Innovative Drug Discovery Infrastructure

CPRIT Core Facility award for establishing the CIDD drug discovery infrastructure including medicinal chemistry laboratories, CRISPR screening platform, and computational drug design capabilities.

$6,000,0002018–2023completed

PI: Dr. Stanton McHardy | RP180770

Recruitment of Drug Discovery Scientists to CIDD

CPRIT Recruitment award supporting the hiring of senior drug discovery scientists and their research programs to expand CIDD capabilities in PROTAC chemistry, computational biology, and translational pharmacology.

$6,000,0002022–2027active

PI: Dr. Daohong Zhou | RR220050

Research Funding

Funding sources supporting CIDD and oncology research

Funding Sources

CPRIT — PROTAC Platform Development

2020–2025

$11M

awarded

CPRIT — CIDD Infrastructure Award

2018–2023

$6M

awarded

CPRIT — Drug Discovery Recruitment

2022–2027

$6M

awarded

NCI R01 — BCL-XL Degradation in Hematologic Malignancies

2019–2024

$2.8M

awarded

NCI R01 — PROTAC Approaches to Overcome Venetoclax Resistance

2022–2027

$2.5M

awarded

DoD CDMRP — PROTAC Degraders for Prostate Cancer

2021–2024

$1.2M

awarded

NCI P30 Cancer Center Support Grant (shared)

2023–2028

$3.2M (CIDD component)

awarded

Dialectic Therapeutics Sponsored Research

2021–2026

$4.5M

awarded

CIDD Leadership

Leadership driving drug discovery and development

Dr. Daohong Zhou
CIDD Co-Director, Professor of Pharmacology

UT Health San Antonio

Department of Pharmacology

Targeted protein degradation (PROTACs)BCL-XL biology and apoptosisRadiation biology and radioprotectionSenolytic drug developmentE3 ligase-based drug design
Inventor180 publications
Dr. Stanton McHardy
CIDD Co-Director, Professor of Medicinal Chemistry

UT Health San Antonio

Department of Pharmacology

Medicinal chemistry and drug designPROTAC chemistry and SAR optimizationCRISPR functional genomicsHit-to-lead and lead optimization campaignsProcess chemistry and CMC development
Collaborator95 publications
Dr. Hong-yu Li
Professor of Medicinal Chemistry

UT Health San Antonio

Department of Pharmacology

Chemical biologyEndocytic mechanismsSmall molecule drug discoveryChemical probes for cell biologyReceptor-mediated endocytosis
Collaborator120 publications