With advances in chemically induced proximity technologies, heterobifunctional modalities have been successfully advanced to clinics for treating cancer. However, pharmacologic activation of tumor-suppressor proteins for cancer treatment remains a major challenge. Here, we present a novel Acetylation Targeting Chimera (AceTAC) strategy to acetylate the p53 tumor suppressor protein. AceTAC is a heterobifunctional small molecule that induces selective acetylation of a POI in endogenous cellular systems by hijacking a lysine acetyltransferase. We discovered the first p53Y220C AceTAC, MS78, which recruits histone acetyltransferases p300/CBP to acetylate the p53Y220C mutant. We additionally performed structure-activity-relationship to assess how acetyltransferase recruitment and p53 acetylation is impacted by AceTAC linker length. Finally, we harnessed TAF1 as a novel acetyltransferase to develop a novel and more potent AceTAC for the treatment of cancer. As a highly innovative technology and a new therapeutic modality, AceTAC directed toward p53Y220C enhance acetylation, promote DNA binding, and rescue transcriptional activity in cellular models, underscoring a novel paradigm shift: chemical restoration of mutant p53 acetylation can be more effective than small-molecule stabilizers alone in reestablishing tumor suppressor functions.

Md Kabir was born in Bangladesh and came to the United States in 2007 through the Diversity Visa (DV) Lottery program. Md and his family moved from state to state and then finally settled in New York City. Md learned English as his fifth language growing up in the Bronx.

Md became the first one in his family to graduate Magna Cum Laude with a B.S. in Chemistry (focus in Biochemistry) from the City College of New York in 2016. During college, Md worked on cladribine derivatives as novel therapeutic agents for the treatment of melanoma. Upon graduating, Md a research fellowship at the National Center for Advancing Translational Sciences (NCATS/NIH). As part of the IQ Consortium (IQC) for the drug efficacy and toxicity testing, Md worked on understanding infant-specific metabolizing enzyme, CYP3A7 and identify substrates, inhibitors, and metabolite with the Toxicology in the 21st Century (Tox21) group. Md’s work showed that while adult-specific CYP3A4 enzyme can metabolize nearly 50% of all drugs, CYP3A7 was only able to metabolize 22% of the compounds, showing potential safety concern particularly since FDA-approved drugs in adults are often administered off-label to neonates and infants.

After understanding how to make safe drug treatment at NIH, Md attended the Icahn School of Medicine at Mount Sinai (ISSMS) in 2019 where he was recruited by world-renowned Dr. Jian Jin. Md wanted to now develop next-generation therapeutics for people afflicted by cancer. Md’s work has led to the discovery of a novel, first-in-class lactate dehydrogenase (LDH) degrader, MS6105, for the treatment of pancreatic cancer. Additionally, Md worked on developing novel technology for targeting undruggable proteins in cancer which led to the discovery of a first-in-class polycomb repressive complex (PRC1) degrader, MS147. Furthermore, Md co-invented Acetylation Targeting Chimera (AceTAC) platform technology for turning on our body’s endogenous tumor suppressor protein, p53 for the treatment of cancer. Md discovered a novel, first-in-class AceTAC MS78, which suppressed proliferation of cancer cells harboring the p53Y220C mutation. Md graduated with a Ph.D. in Biomedical Sciences in the Pharmacology and Therapeutics Discovery (PTD) track in 2023.

Md is finishing his postdoctoral studies with Dr. Jian Jin and Dr. Yi Shi to develop novel single-domain drug conjugates. Furthermore, Md is advancing novel therapeutic strategy that can not only degrade oncogenic protein but can also reactivate tumor suppressor at the same time.

In his time at Mount Sinai, Md has won several awards including, (1) National Cancer Institute (NCI) T32 Training Postdoctoral Grant in Cancer Biology (2024-2026) (2) Mount Sinai Trainee Postdoctoral Innovation Award (2023) (3) Mount Sinai Department of Pharmacological Sciences - Jack P. Green Presentation Award (2023) (4) Excellence in Entrepreneurship and Innovation (2021). Md was also an invited speaker at several institutions in 2025 including: (1) TPD and Induced Proximity Symposium by Promega (2) Fudan University in Shanghai, China and (3) Kangwon National University in South Korea.

Md teaches first-year medical students at the Icahn School of Medicine at Mount Sinai and volunteers in his free time. Md is a certified scuba diver, likes to travel and explore new food restaurants with friends.