# Synthetic Studies Related to Cancer Research/Treatment

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $427,796

## Abstract

Project Summary/Abstract:
This renewal involves integrated and interdependent synthetic, mechanistic, structural, biochemical
mode of action, computer modeling, collaborative and preclinical studies directed at the design,
synthesis, assay and advancement of fundamentally new and unique therapeutic leads and strategies
directed at unsolved global human health problems: the eradication of HIV/AIDS, novel treatments for
Alzheimer's disease and multiple sclerosis, and the use of small molecules to enhance antigen density in
antigen-targeted CAR T/NK cell therapies and cancer immunotherapy. HIV is one of the most
catastrophic pandemics to confront mankind. Current antiretroviral therapy (ART) addresses the active
virus, allowing one to live with HIV/AIDS, but with cost, compliance, resistance and chronic
chemoexposure challenges. ART is not curative. Reservoir cells incorporating genomically encoded
provirus episodically resupply the active virus. Elimination of these reservoir cells if done with ART is
thus one of the most promising strategies to eradicate HIV/AIDS. Modulation of protein kinase C (PKC)
represents one of the best strategies to activate reservoir cells for subsequent clearance by the immune
system, antibodies or immunotoxins. PKC modulators are also leading candidates for treating
Alzheimer's disease (in current clinical trial), for cancer immunotherapy (clinical trial proposed for 2021),
for multiple sclerosis and for many other unmet therapeutic needs. The lead PKC modulator, bryostatin
1, has been entered into clinical trials for AIDS eradication and Alzheimer's disease and is expected to
be used clinically in a CRADA conducted by NCI scientists to enhance antigen expression in antigen
targeted CAR T cell therapies for children with acute lymphoblastic leukemia who fail cell therapy
because of low antigen density. Enabled by our scalable (now GMP) synthesis of bryostatin which
represents the sole major supply of clinical grade material and our computational and REDOR solid state
NMR structural studies relevant to bryostatin binding to PKC, plans are presented for the design,
synthesis and evaluation of uniquely accessible “close-in” bryostatin analogs, super simplified analogs
and two new families of clinically relevant PKC modulators, collectively directed at the identification of
more efficacious, better tolerated and more synthetically accessible clinical candidates. New candidates
will be evaluated in a range of “in house” assays and in advanced assays conducted by a network of
collaborators expert in the clinically targeted areas.

## Key facts

- **NIH application ID:** 10426401
- **Project number:** 2R01CA031845-41A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** PAUL Anthony WENDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $427,796
- **Award type:** 2
- **Project period:** 1981-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426401

## Citation

> US National Institutes of Health, RePORTER application 10426401, Synthetic Studies Related to Cancer Research/Treatment (2R01CA031845-41A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10426401. Licensed CC0.

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