Phosphatidylinositol 3-Kinase (PI3K) Targeted Library

Phosphatidylinositol 3'-kinase (PI3K) is a lipid kinase and the signaling pathway is a regulatory pathway that controls various processes such as cell proliferation, survival, migration, and metabolism. P13K plays a key role in a variety of biological and pathophysiological processes, particularly in oncogenesis and drug resistance in cancer, and is therefore a promising therapeutic target for cancer. The catalytic and regulatory subunits of class I PI3Ks have oncogenic potential: Class I PI3Ks have the unique ability to produce phosphatidylinositol 3,4,5 trisphosphate (PIP(3)). The catalytic subunit p110α and the regulatory subunit p85 undergo cancer-specific gain-of-functional mutations, resulting in enhanced enzymatic activity, constitutive signaling ability and oncogenicity.

BOC Sciences is focused on developing a high-quality p13K targeted library to discover potential antitumor PI3K inhibitors.

Figure 1. The phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR). (Shunfei, Y.; et al. 2017)

Library Design

BOC Sciences has applied a variety of available structural information to design a focused library of PI3K inhibitors using a receptor-based approach to provide a variety of promising anticancer agents.

1. Firstly, we determine the structure of PI3K by employing many X-ray structures published in the database
2. Then, accurate molecular docking is performed based on the data in the PDB entry
   The following amino acid residues are identified for Unity query feature preparation:
   1) Responsible for the formation of polar contacts: Val822, Tyr 867, Asp836, Asp841, Lys833
   2) Responsible for hydrophobic interactions: Leu845, Tyr876, Ile879, Ile936
3. BOC Sciences compound sets will be further filtered using Rules of Five and PAINS structure filters
4. A virtual screening is conducted against the ligand datasets prepared from the resulting compounds, where the filtering procedure is initiated by a flexible search
5. Finally, we design the QFit score data for extracting hit compounds and preparing the final PI3K targeted library

Phosphatidylinositol 3-Kinase (PI3K) Targeted Library Characteristics

• The Unity Query Model of protein binding site is built and validated by docking of co-crystallized ligand with RMSD value of 1.3 Å
• Favorable physicochemical parameters and solubility requirements
• 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
• Compound cherry-picking service is provided

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 Phosphatidylinositol 3-Kinase (PI3K) Targeted Library design at competitive prices for global customers. Personalized and customized services of Phosphatidylinositol 3-Kinase (PI3K) Targeted 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!