Briefly explain how BCI-2 and MCL-1 inhibitors help in cancer treatment. Give examples (two each) of BCI-2 and MCL-1 inhibitors

Bcl-2 and Mcl-1 are anti-apoptotic proteins that belong to the Bcl-2 family, which controls the process of programmed cell death or apoptosis. In many types of cancers, these proteins are found in high levels. Because of this, the cancer cells avoid apoptosis, even when they are damaged or abnormal. This helps the cancer cells survive for a long time, grow uncontrollably and become resistant to chemotherapy or radiation.

To stop this abnormal survival of cancer cells, scientists have developed special drugs called Bcl-2 inhibitors and Mcl-1 inhibitors. Bcl-2 and Mcl-1 inhibitors are special drugs that block the action of these anti-apoptotic proteins. When these proteins are blocked, the cancer cells lose their ability to avoid apoptosis. As a result, the natural process of cell death restarts. These inhibitors allow the pro-apoptotic proteins (like Bax and Bak) to become active again, which helps in triggering the death of cancer cells.

By doing this, these inhibitors help shrink tumors and reduce the spread of cancer. They also make cancer cells more sensitive to other therapies. That is why these inhibitors are often used in combination with chemotherapy or targeted therapy to improve the overall effect of treatment.

So, the main way Bcl-2 and Mcl-1 inhibitors help in cancer treatment is by removing the protection that cancer cells have against cell death, allowing them to die naturally and stop multiplying. This improves the success of cancer treatment and may also reduce relapse or resistance.

Examples of Bcl-2 Inhibitors

1. Venetoclax (ABT-199):
  • It is a highly selective Bcl-2 inhibitor approved for treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). It binds directly to the Bcl-2 protein and prevents it from protecting the cancer cell. By doing this, it promotes apoptosis and helps reduce tumour burden, especially in blood cancers.
2. Obatoclax:
  • This is a broad-spectrum Bcl-2 family inhibitor that can target multiple anti-apoptotic proteins including Bcl-2, Bcl-xL and Mcl-1. It has been tested in clinical trials for leukemia, lymphoma and some solid tumours. It increases the sensitivity of cancer cells to chemotherapy by promoting apoptosis.

Examples of Mcl-1 Inhibitors

1. S63845:
  • It is a selective Mcl-1 inhibitor that binds strongly to Mcl-1 protein and blocks its anti-apoptotic action. This allows Bax and Bak to become active and induce apoptosis. It is effective against cancers that depend mainly on Mcl-1 for survival like multiple myeloma, AML and some solid tumours.
2. AZD5991:
  • This is a potent Mcl-1 inhibitor developed for treating hematologic malignancies such as leukemia and myeloma. It promotes apoptosis by targeting Mcl-1 and is currently under clinical trial studies for its safety and effectiveness.





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