IAP Inhibitors Library

Inhibitor of apoptosis (IAP) proteins are a family of anti-apoptotic proteins that play an important role in evasion of apoptosis because they both block apoptotic signaling pathways and promote survival. Eight members of this family have been described in humans, and they act by regulating signal transduction pathways, cytokine production and cell survival to regulate innate and adaptive immunity. The regulation of immunity by the IAPs is mainly mediated through the ubiquitin ligase functions of cIAP1, cIAP2 and XIAP, whose targets affect the NF-κB and MAPK signaling pathways. Moreover, IAP is able to regulate cystathione and thus plays a key role in determining cell fate. Members of the IAP protein family are frequently overexpressed in cancer and contribute to tumor cell survival, chemo-resistance, disease progression and poor prognosis.

Aiming to develop attractive therapeutic approaches for novel cancer therapies, BOC Sciences has designed small molecules that mimic the binding of the endogenous IAP antagonist second mitochondria-derived activator of caspases/direct IAP-binding protein with low pI (Smac/DIABLO) to a shallow groove on the surface of select IAP baculoviral IAP repeat (BIR) domains.

Figure 1. Summary model of IAPs in IBD. (Pedersen, J.; et al. 2014)

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: 3UW5
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: ASP138, GLN132, GLN132, TRP147
3. Finally, 661 potential IAP inhibitors selected with computational chemistry and virtual screening techniques are generated successfully

Figure 2. Formation of the inflammasome and caspase-1 activity. (Pedersen, J.; et al. 2014)

IAP 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 3. The canonical and non-canonical NF-kB pathways. (Pedersen, J.; et al. 2014)

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 IAP Inhibitors Library design at competitive prices for global customers. Personalized and customized services of IAP 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!