Diacylglycerol kinases (DGK or DAGK) are a family of kinases capable of catalyzing the phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PA) by using ATP, and both DAG and PA are lipids with important structural and signaling properties. DGK isoforms with specific structures have important roles in the control of membrane structure, signaling complexes and intercellular communication. Different isoforms of DGK therefore contribute differently to human diseases, and scientists have developed a variety of therapeutic approaches to modulate DGK function. In particular, DGK is highly expressed in hepatocellular carcinoma and melanoma cells, so inhibitors targeting DGK activity hold particular promise in the fight against cancer.
BOC Sciences is focused on developing a high-quality DGK inhibitors library to deliver 12,000 compounds.
Figure 1. DGKs contribute to local modulation of DAG and PA levels during cell-cell and cell-ECM contact. (Merida, I.; et al. 2019)
Library Design
At BOC Sciences, a DGK inhibitor library is designed and constructed by employing the CADD approach based on the corresponding characteristics of DGK.
- Firstly, more than 880 DGK inhibitor molecules are collected as template molecules
- Then, the stocked small molecules of BOC Sciences are used to screen with 3D-pharmacophore modeling and substructure screening/Isosteric morphing approaches, respectively.
- Docking study is carried out by employing the template mode and excluded volumes
- We integrate the pharmacophore into the X-ray structure after performing the dynamic docking procedure with the template molecule
- Our teams carefully determine the binding site
- Good alignment can be achieved
- Finally, 12,000 kinds of drug-like compounds with the potential to become DGK inhibitors are delivered
DGK Inhibitors Library Characteristics
- Molecular docking prediction screening of high potential molecules is conducted by using 3D pharmacophore modeling combined with DGK protein domains
- 2D substructure search/allele substitution method are provided to find structural analogs
- 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
Figure 2. High DGKα expression in tumors and tumor-infiltrating T cells. (Merida, I.; et al. 2019)
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 DGK Inhibitors Library design at competitive prices for global customers. Personalized and customized services of DGK 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!
Reference
- Merida, I.; et al. Diacylglycerol Kinase Malfunction in Human Disease and the Search for Specific Inhibitors. Handbook of Experimental Pharmacology. 2019.
