BCL-2 Inhibitors Development Services

Alfa Cytology helps you develop and optimize inhibitors for BCL2 proteins. After developing novel BCL2 inhibitors, we can assist in the development and optimization of biochemical or cell-based tests to evaluate the activity and potency of BCL-2 inhibitors. In addition to designing and validating BCL2 inhibitors, we can determine the binding of CL2 inhibitors to BCL-2, inhibit BCL-2 function, or induce apoptosis.

Functional Roles of BCL-2 in Leukemia

The function of BCL-2 is to protect cells from undergoing apoptosis when it is overexpressed. Its primary role is to inhibit the initiation of apoptosis by preventing the activation of key cell death effector proteins called BAX and BAK. These proteins, when activated, trigger the release of cytochrome C and the activation of caspases, leading to cell destruction through apoptosis. Many hematological malignancies exhibit altered expression of BCL-2 or related proteins, or a loss of proapoptotic proteins. This deregulation disrupts the balance between prosurvival proteins (such as BCL-2) and proapoptotic proteins, leading to increased cell survival and resistance to cell death signals.

Fig. 1. Inhibiting BCL2 with venetoclax in hematological malignancies. (Roberts, A.W., 2020)

BCL-2 is an inhibitor of apoptosis that can inhibit apoptosis in a variety of cell systems and therefore plays a pivotal role in cancer therapy development. Alfa Cytology provides comprehensive BCL-2 inhibitor development services.

Discovery of a Novel BCL-2 Inhibitor

• Virtual screening was conducted using a QSAR classification and regression model to identify potential BCL-2 inhibitors.
• Based on the BCL-2 homology (BH) domain, an inhibitor that selectively interacts with BCL2 is designed. We can provide a variety of target designs, including those targeting BCL-2's BH1-4 domain.
• The benzenesulfonamide fragment can interact with the hydrogen bond of Gly145 of Bcl-2, which contributes to the selectivity of BCL-2. We can design and synthesize novel inhibitors based on acyl sulfonamides according to their binding sites, and evaluate their activity as BCL-2 inhibitors.
• Bcl-2 is resistant to Venetoclax due to mutations in Gly101Val (G101V) and Asp103Tyr (D103Y). We can design highly effective inhibitors targeting mutation sites for you to provide new insights into the treatment of BCL-2 dependent and Venetoclax-resistant hematological cancers.

Identification of a Novel BCL-2 Inhibitor in Leukemia

We provide surface plasmon resonance technology to verify the interaction between BCL-2 and a novel BCL-2 inhibitor, provide effective information on the targeting combination of a novel BCL-2 inhibitor and BCL-2, and further evaluate or optimize BCL-2 inhibitors.

Evaluation of BCL-2 Inhibitors

ABT-199 can be used as a positive control to explore the inhibitory effect and therapeutic effects of a novel BCL-2 inhibitor on leukemia. We can analyze the in vivo and in vitro assays of a novel BCL-2 inhibitor for you to evaluate its inhibitory effect.

Advantages of Our Services

• We boast a highly skilled team of drug molecular designers.
• Our team possesses vast experience in the design and development of inhibitors.
• We offer experimental services that yield significant inhibitory effects.
• We have devised an efficient method for drug screening.
• Our extensive drug database and advanced analysis platform provide invaluable resources.

Alfa Cytology provides discovery services for BCL-2 inhibitors. Using our expertise in leukemia-targeted drugs, we can save you time and money in the development of your drug. The services we provide help you screen and optimize BCL-2 inhibitors and explore new targeted drugs for the treatment of AML and CLL. Please contact us if you are interested in our services or would like to know more.