Bcl2-PPI Inhibitors Library

The Bcl-2 family proteins regulate cell death by controlling the integrity of the outer mitochondrial membrane. Pro-apoptotic Bcl-2 family of proteins, such as BAK and BAX, play a crucial role in apoptosis. Nowadays, small molecules that disrupt this interaction by binding to the anti-apoptotic Bcl-2 family proteins have been designed to induce apoptosis in cancer cells. Proteins in the Bcl-2 family are central regulators of programmed cell death, members that inhibit apoptosis such as Bcl-2 are overexpressed in many cancers, and contribute to tumorigenesis, progression, and resistance to therapy. In other words, reduction in Bcl-2 increases sensitivity to anti-cancer drugs and improves in vivo survival. There are two types of Bcl-2 family inhibition strategies currently being explored at the clinical trial stage: one is to use antisense-based strategies to knock down Bcl-2 expression, and the other one is to synthesize BH3 mimics that contain a novel class of Bcl-2 inhibitors. The acceptance that many cancers depend on antiapoptotic Bcl-2 proteins, and that Bcl-2 proteins interact through defined Bcl-2-homology (BH) domains prompt the development of drugs that mimic the action of the BH3 domain as they are able to restore apoptosis through the binding to one or more Bcl-2 family members.

BOC Sciences is focused on designing small molecules that disrupt this interaction by binding to the anti-apoptotic BCL-2 family proteins.

Figure 1. Main pathways of BCL2 regulation in MI/RI. (Korshunova, A. Y.; et al. 2020)

Library Design

At BOC Sciences, our experts have established a high-throughput virtual screening method based on molecular docking approach to generate this library:

1. A receptor-based virtual screening process is created based on X-ray data for the complexes: 6GL8
2. The compounds in the HTS compound collection have been pre-filtered using BOC Sciences' internal filters and then docked at the active site. Moreover, we have considered a variety of H-bond constraints: ALA149, GLU136, GLN118, ASP111
3. Finally, 1,680 potential Bcl2-PPI inhibitors selected with computational chemistry and virtual screening techniques are generated successfully

Bcl2-PPI Inhibitors Library Characteristics

• No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
• Bioactivity and safety confirmed by preclinical studies and clinical trials
• Structural diversity, medicinal activity, and cellular penetration
• Structural document, IC₅₀, and other chemical and biological data are provided
• All compounds are continually updated
• All of these compounds with Tanimoto index ≥ 0.85
• Compound cherry-picking service is provided

Figure 2. Effects of IPC and IPostC on BCL2-regulated apoptosis in MI/RI. (Korshunova, A. Y.; et al. 2020)

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR and HPLC
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Bcl2-PPI Inhibitors Library design at competitive prices for global customers. Personalized and customized services of Bcl2-PPI Inhibitors Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!