CDK7 inhibitors draw attention as next-generation anticancer drugs… Pharmaceutical industry joins in development

(Health Korea News / Lee Chung-man) As CDK7 inhibitors are gaining attention as next-generation anticancer drugs, pharmaceutical companies are jumping into the development of treatments one after another.

The CDK protein family is a major enzyme that controls the cell cycle, and is activated by binding to a protein called cyclin. Among the CDK proteins, CDK7 plays a role in activating a DNA replication factor called RNA polymerase II during the DNA replication process.

Therefore, CDK7 is like a switch that can initiate replication of specific DNA. When CDK7 is overexpressed, it causes certain cells to divide and grow more quickly, which increases the possibility of tumorigenesis. Even after tumors have already developed, CDK7 contributes to tumor cell proliferation.

Although the existence of CDK7 was discovered in 1990, it was not until the late 2010s that the relationship between CDK7 and tumor cells was clearly elucidated, and it emerged as a target for anticancer drugs.

CDK7 inhibitors are targeted anticancer drugs under development based on these prospects. It is an approach to treat various cancers by inhibiting CDK7. In particular, it is expected to be an innovative new drug as it is known to be overexpressed on the surface of tumor cells of intractable cancers for which target antigens are still unclear, such as triple-negative breast cancer, ovarian cancer, and pancreatic cancer.

According to our investigation, there are currently 41 CDK7 inhibitors under development. Of these, 9 drugs have entered clinical trials.

#Carrick Therapeutics of Irelandis speeding up commercialization by conducting phase 2 clinical trials for its CDK7 inhibitor candidate, ‘CT-7001’ (active ingredient: samuraciclib). According to the company, the drug has demonstrated potential therapeutic effects in various fields, including neoplasms, digestive diseases, and respiratory diseases.

The currently designed indications for ‘CT-7001’ include breast cancer, metastatic hormone-refractory prostate cancer, ovarian cancer, small cell lung cancer, pancreatic cancer, and acute myeloid leukemia.

The first development institution for this drug was Emory University in the United States, and Carrick Therapeutics secured ‘CT-7001’ by signing a licensing agreement with Emory University in 2016.

The U.S. Food and Drug Administration (FDA) designated ‘CT-7001’ as a fast-track development drug for breast cancer in August 2021.

#Korea’s Curient We are also working on the development of our own CDK7 inhibitor candidate, ‘Q901’. ‘Q901’ inhibits CDK7, thereby inhibiting DNA damage repair in tumor cells and increasing genomic instability, thereby inducing cell death.

Unlike other developers, this company is attempting to develop ‘Q901’ as a combination therapy that can overcome antibody-drug conjugate (ADC) resistance.

ADC is a drug product that connects an antibody and a cytotoxic drug with a linker. It is a drug that causes local cytotoxicity by combining a highly target-selective antibody to improve the cytotoxic side effects of first-generation chemotherapy drugs. It has established itself as an effective treatment option for patients with intractable cancer who do not respond to targeted anticancer drugs and immunotherapy drugs.

However, unlike systemic chemotherapy drugs, ADCs act locally and are therefore not free from the problem of resistance due to the ever-changing mutations of tumor cells. Qurient plans to solve the problem of ADC resistance by using ‘Q901’ in combination.

Specifically, tumor cells acquire resistance to treatment by changing their gene expression patterns, and co-administration of ‘Q901’ can reduce resistance by inhibiting the change in the gene expression pattern of tumor cells through the CDK7 inhibition mechanism.

In June 2023, Qurient received approval for the Phase 1/2 clinical trial plan (IND) for ‘Q901’ from the Ministry of Food and Drug Safety. The trial will evaluate the monotherapy of ‘Q901’ and the combination therapy of MSD’s immune checkpoint inhibitor ‘Keytruda’ (active ingredient: pembrolizumab) + ‘Q901’ in up to 128 patients with advanced solid tumors.

If the current trend continues, the first CDK7 inhibitor is expected to be introduced to the world around 2027.

Copyright © Health Korea News. Unauthorized reproduction and redistribution prohibited.