Shuttle Pharma’s HDAC Inhibitor Halts ER+ Breast Cancer Growth via ATM Activation, ER Modulation

On July 19, 2024, Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH), also known as Shuttle Pharma, announced the publication of a significant manuscript regarding one of their pre-clinical assets, SP-1-303. This compound is a histone deacetylase (HDAC) inhibitor that has shown promising results in the inhibition of estrogen receptor positive breast cancer cells (ER + BC).

The manuscript, titled "Dual-targeting class I HDAC inhibitor and ATM activator, SP-1-303, preferentially inhibits estrogen receptor positive breast cancer cell growth," was authored by Dr. Mira Jung of Georgetown University Medical Center, along with Dr. Scott Grindrod, Shuttle Pharma’s Principal Scientist. It was published in PLOS ONE, a peer-reviewed open-access journal by the Public Library of Science (PLOS).

SP-1-303 was discovered and synthesized in Shuttle Pharma’s laboratories by Dr. Grindrod. This pre-clinical selective Class I HDAC inhibitor targets HDAC1, 3, and 6, presenting direct cellular toxicity against ER + BC while sparing normal tissues. HDAC inhibitors generally enhance the sensitivity of cancer cells to radiation, protect normal tissues from radiation damage, and activate the immune system. Specifically, SP-1-303 also increases the PD-L1 expression level over time, suggesting its potential to be used in combination with immune checkpoint blockers to boost therapeutic outcomes.

Dr. Anatoly Dritschilo, CEO of Shuttle Pharmaceuticals and a co-author of the report, emphasized the importance of this dual-targeting strategy. He stated, “Inhibition of cancer cell growth with little effect on surrounding normal cells is the desired strategy for treatment of cancers.” The report illustrates that SP-1-303, by targeting Class I HDACs and ATM, offers a promising therapeutic approach for treating ER + BC, warranting further preclinical evaluation as a potential treatment option.

Shuttle Pharma, founded in 2012 by faculty members of Georgetown University Medical Center, is focused on developing therapies to improve the outcomes for cancer patients treated with radiation therapy (RT). The company's mission is to enhance the lives of cancer patients by creating treatments that maximize the effectiveness of RT while minimizing its side effects. Although RT is an established method for treating cancers, Shuttle Pharma aims to develop radiation sensitizers that increase cancer cure rates, extend patient survival, and improve the quality of life. These sensitizers can be utilized as a primary treatment or in combination with surgery, chemotherapy, and immunotherapy.

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