# Michigan Rogel Cancer Center: DALTAC molecule links AR and p300, ~1,000 times more potent in tumor cells in preclinical tests

- Published: 2026-11-12 08:46 UTC
- Section: Life & Health › Medicine
- Tags: domain-alteration chimeras, DALTAC-1, prostate cancer, androgen receptor, p300 coactivator, chemically induced proximity, castration-resistant prostate cancer, bifunctional small molecule, Rogel Cancer Center, preclinical study
- URL: https://realtech.media/news/rt-1eae63a051fc5726727793c2_michigan_rogel_cancer/

**Michigan researchers joined two cancer-driving proteins with a bifunctional molecule. In cell, organoid and mouse studies it suppressed prostate tumor growth; the work is preclinical.**

![Michigan Rogel Cancer Center: DALTAC molecule links AR and p300, ~1,000 times more potent in tumor cells in preclinical tests](https://realtech.media/media/2026/11/705e24a154c42666.jpg)
*Diane A. Reid (Photographer), Wikimedia Commons, Public domain*

Researchers at the University of Michigan Health Rogel Cancer Center have described a preclinical strategy against prostate cancer that rewires the interaction of two cancer-driving proteins. The study, published in Nature and reported by bioengineer.org, shows that gluing the androgen receptor (AR) and the transcriptional coactivator p300 into an abnormal configuration acted more strongly against tumor cells than conventional inhibition, while sparing normal cells in the tests [1].

The platform is called DALTAC, for domain-alteration chimeras. Instead of blocking the binding between AR and p300, the team built a bifunctional small molecule that ties them together. Senior author Arul M. Chinnaiyan said the compound acts like a molecular brace that holds the proteins in an unnatural arrangement and keeps them inactive [1].

## How the chimeras work

Each molecule consists of two targeted inhibitors joined by a carefully measured short chemical linker, as noted by co-senior author Shaomeng Wang. Tethering AR to p300 alters the spatial relationship and the native functions of both targets and, according to the authors, switches off two oncogenic signaling pathways at once. Unlike PROTACs, which recruit cellular machinery to degrade proteins, DALTAC does not degrade its targets. It belongs to the field of chemically induced proximity [1].

The prototype compound is designated DALTAC-1. The authors report that healthy cells lack the cooperative AR–p300 assemblies that drive tumors, which explains the selectivity [1].

## Results in the laboratory

The molecules were tested in cultured prostate cancer cell lines, mouse models and three-dimensional organoids derived from patient tissue. According to Wang, the optimized lead molecule was about 1,000 times more potent in tumor cells than the combination of separate AR and p300 inhibitors. It was also chemically optimized for oral bioavailability, which could allow a tablet form in the future [1].

In animal models the chimeras produced durable responses and remained effective against tumor lines resistant to standard therapies. Chinnaiyan said these results point to a possible route for advanced and castration-resistant prostate cancer, provided they translate to humans [1].

The work remains at the preclinical stage. Both groups, the Chinnaiyan laboratory (prostate cancer biology) and the Wang laboratory (medicinal chemistry), are refining candidates for future clinical trials. The authors also suggest that the approach could serve as a general framework for designing molecules against oncogenic protein complexes in other cancers [1].

## Sources

1. [bioengineer.org](https://bioengineer.org/domain-alteration-chimera-strategy-suppresses-prostate-tumor-growth-in-preclinical-tests)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-1eae63a051fc5726727793c2_michigan_rogel_cancer/