Bcl 2 Human (minus BH4 domain)

B-Cell Leukemia/Lymphoma 2 (BCL-2) is a crucial protein involved in the regulation of apoptosis, or programmed cell death. It is part of a larger family of proteins that play significant roles in cell survival and apoptosis. The human recombinant form of BCL-2, particularly the BH4 domain, has been extensively studied for its role in various cancers, especially B-cell lymphomas and leukemias.

BCL-2 is an anti-apoptotic protein that resides in the outer mitochondrial membrane. It functions by inhibiting the release of cytochrome c, a key component in the apoptotic pathway. The BH4 domain of BCL-2 is essential for its anti-apoptotic activity. This domain interacts with pro-apoptotic proteins, preventing them from triggering cell death.

The dysregulation of BCL-2 is a hallmark of many cancers, particularly B-cell lymphomas and leukemias. Overexpression of BCL-2 leads to increased cell survival and resistance to chemotherapy. This makes BCL-2 a critical target for cancer therapy. Inhibitors of BCL-2, such as venetoclax, have shown significant efficacy in treating chronic lymphocytic leukemia (CLL) and other B-cell non-Hodgkin lymphomas .

Targeting BCL-2 has been a challenging yet promising approach in cancer therapy. Early attempts to inhibit BCL-2 were met with limited success due to toxicity and lack of efficacy. However, recent advancements have led to the development of highly selective BCL-2 inhibitors. Venetoclax, for example, has been approved for use in CLL and has shown notable activity in other B-cell malignancies .

The development of BCL-2 inhibitors has been driven by a deeper understanding of the protein’s structure and function. Research has focused on identifying compounds that can selectively bind to the BH4 domain and inhibit its anti-apoptotic activity. Additionally, combination therapies involving BCL-2 inhibitors and other agents are being explored to enhance treatment efficacy and overcome resistance mechanisms .