Samjin Pharmaceutical Headquarters Building [사진=헬스코리아뉴스 D/B]
[헬스코리아뉴스 / 이순호] It has been confirmed that Samjin Pharmaceutical is conducting research by discovering candidate substances for TEA domain (TEAD) inhibitors, which have recently been attracting attention as new anti-cancer targets. Some animal testing has already been conducted to evaluate efficacy. While only a few domestic pharmaceutical and bio companies are still developing TEAD inhibitors, attention is focused on whether Samjin Pharmaceutical will join the ranks of developing related treatments in earnest.
According to the Korean Intellectual Property Office on the 20th, Samjin Pharmaceutical is in the process of registering a patent for the invention of ‘novel heterocyclic compound and pharmaceutical composition containing the same’.
This invention relates to a new small molecule compound that inhibits gene overexpression by the ‘Hippo signaling pathway’ by inhibiting palmitoylation of TEAD proteins. It was applied for in March and the specification was recently published.
The Hippo signaling system is known to play a role in regulating the number of cells within the normal range in tissues in vivo. When mutations occur in the constituent proteins of the pathway, regulatory substances called YAP and TAZ are activated as key transcription factors (in specific regions of DNA). It binds with TEAD, a protein that promotes or suppresses gene expression, and causes various diseases, including cancer.
TEAD proteins undergo a post-translational modification process called palmitoylation, which promotes binding to YAP or TAZ proteins. Taking this into consideration, pharmaceutical companies are conducting research on small molecule compounds that inhibit palmitoylation of TEAD proteins and thereby inhibit gene overexpression by the Hippo signaling system.
According to the application specification published by the Korean Intellectual Property Office, the new candidate discovered by Samjin Pharmaceutical is structurally completely different from existing TEAD protein palmitoylation inhibitors and has excellent intracellular penetration and in vivo stability.
Samjin Pharmaceutical evaluated the maximum concentration (GI50) value at the moment when the proliferation of cancer cells is reduced by half through cell experiments (in vitro). The new compound discovered by the company reduced the proliferation of cancer cells by 50% even at a very low concentration of 0.03μM. reduced to .
Samjin Pharmaceutical also conducted animal tests with this compound. The anticancer efficacy was evaluated using an NF2-deficient mesothelioma xenograft mouse model. The new compound discovered by the company not only showed excellent tumor suppressive activity but also did not cause weight loss or death in test animals, making it a safe cancer drug without drug toxicity. The potential for development as a preventive or therapeutic agent has been confirmed.
Hanmi Pharmaceutical and Bridge Bio are also developing TEAD inhibitors.
Initial research data released for the first time at an overseas academic conference
In addition to Samjin Pharmaceutical, companies currently developing TEAD inhibitors in Korea include Hanmi Pharmaceutical and Bridge Bio, a company specializing in new drug development. Both companies are still in the early research stages, and their pipelines were revealed for the first time at an international academic conference held this year.
Hanmi Pharmaceutical announced initial research results on a TEAD inhibitor lead material at the American Association for Cancer Research (AACR2023) held in Orland, USA in April.
This lead substance was found to effectively inhibit tumor growth within an acceptable dose as a result of testing using a tumor mouse model, and its safety profile was confirmed in cell experiments.
Hanmi Pharmaceutical plans to conduct additional preclinical research and GLP toxicity testing after establishing candidate substances for preclinical use.
Bridge Biotherapeutics first unveiled its TEAD targeting inhibitor candidate ‘BBT-4437’ at the ‘2023 AACR-NCI-EORTC’ held in Boston, USA last August. ‘AACR-NCI-EORTC’ is an academic conference jointly hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI), and the European Association for Cancer Research (EORTC).
‘BBT-4437’ is a substance discovered by Boston Discovery Center (BDC), a subsidiary located in Boston, USA, and Bridge Biotherapeutics presented various early experimental data of ‘BBT-4437’ in a poster at this academic conference. did.
The company plans to establish a development strategy for ‘BBT-4437’ in the future by considering various solid carcinomas, such as malignant mesothelioma and tumors containing NF2 mutations.
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2023-09-19 19:41:24
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