# Peptide-based conjugate for a water-insoluble drug treating advanced prostate cancer

> **NIH NIH R01** · UNIVERSITY OF MISSOURI KANSAS CITY · 2020 · $296,991

## Abstract

The phosphoinositide 3-kinases (PI3Ks) signaling pathway is one of the most important pathways in 
cancer, and a number of PI3K inhibitors are currently in preclinical and clinical studies for 
various cancer therapies. We and others have  demonstrated that  the isoform PI3K-p100β is 
essential for tumorigenesis and androgen-independent progression in prostate cancer. TGX-221 is a 
novel, isoform- specific, and potent small molecule inhibitor of PI3K-p100β. While TGX-221, 
therefore, has considerable potential as a novel chemotherapy agent for prostate cancer, its poor 
solubility and lack of selectivity for prostate cancer cells limit its clinical application. We 
have recently synthesized a TGX- 221 derivative, TGX-D1, which contains a hydroxyl group for 
peptide conjugation but exhibits similar activity and isoform-specificity as TGX-221. In this 
project, we will replace the –OH of TGX-D1 with –SH to form TGX-SH, which will have better 
stability in the serum.
The overall objectives of this project are: 1) to develop a novel peptide-modified TGX-SH  to 
overcome the two potential  obstacles of TGX-221, poor solubility  and lack of  specificity to  
prostate cancer cells; 2) to evaluate its therapeutic effectiveness in combination with other 
anti-prostate cancer agents. The long-term goal of this project is to develop a peptide-based 
platform that may be used for not only TGX-SH but also other anti-prostate cancer agents that face 
poor solubility and poor tissue- specificity.
Approximately 40% of new  chemical entities in  drug discovery  are lipophilic and  fail to reach 
market due to poor solubility. Not to mention that lack of tissue specificity is another major 
challenge for most chemical entities. Successful completion of the proposed studies may  provide  a 
 promising concept for other small molecule drugs that face similar clinical challenges, poor 
stability and lack of target-ability.

## Key facts

- **NIH application ID:** 9975195
- **Project number:** 5R01GM121798-04
- **Recipient organization:** UNIVERSITY OF MISSOURI KANSAS CITY
- **Principal Investigator:** Kun Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $296,991
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975195

## Citation

> US National Institutes of Health, RePORTER application 9975195, Peptide-based conjugate for a water-insoluble drug treating advanced prostate cancer (5R01GM121798-04). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9975195. Licensed CC0.

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