A new drug TR128 capsule for advanced malignant solid tumors was approved by National Medical Products Administration (NMPA) for clinical trials recently.
After TR64 and TR115, this is the third innovative targeted drug approved for clinical trials this year. They are all developed by a research team led by Prof. Liu Qingsong from Hefei Institutes of Physical Science of Chinese Academy of Sciences.
Tumors are major diseases that threaten human health, and their pathogenesis is usually closely related to mutations in proto-oncogenes.
Overactivation of RAS-RAF-MEK-ERK, a protein signaling pathway, is one of the most common molecular features of tumorigenesis. Mutations in the RAS gene are present in about 30% of tumors, such as RAS mutations in 95% of pancreatic cancer, 52% of RAS mutations in colorectal cancer, 31% of RAS mutations in non-small cell lung cancer, and 21% of RAS mutations in endometrial cancer.
RAF kinases, including ARAF, BRAF, and CRAF with BRAF as the most investigated among the three, are key downstream signaling proteins of the RAS signaling pathway and the hot spots for tumor mutations.
TR128 represented a new generation of pan-RAF kinase inhibitors that exhibit strong inhibitory effect on BRAFCRAF and BRAF-V600E proteins of the RAF kinase family, and it could overcome the "paradoxical activation" effect seen with current BRAF-V600E inhibitors.
Both in vitro and in vivo experiments showed that TR128 achieved strong inhibition on cell proliferation and induced apoptosis in cells with RAS and RAF mutations such as colorectal cancer, pancreatic cancer, non-small cell lung cancer and melanoma.
It also showed significant inhibition of tumor growth in mouse allogeneic tumor models.
According to the team, TR128 is expected to become a new generation of targeted drugs for the treatment of cancers including colorectal cancer, pancreatic cancer, and non-small cell lung cancer.
The preliminary research and development of the project were supported by the National Natural Science Foundation of China, the "Personalized Medicine" Leading Science and Technology Project of the Chinese Academy of Sciences and other projects, and the industrialization development stage is jointly promoted by Tarapeutics Science Inc.
