Fibroblast Growth Factor Receptor 1 (FGFR1) Tyrosine Targeted Library

The fibroblast growth factor receptor 1 (FGFR1), tyrosine kinase receptor, plays an important role in angiogenesis, embryonic development, cell proliferation, cell differentiation and wound healing. Binding of the FGF to the FGFR tyrosine kinase leads to receptor tyrosine autophosphorylation as well as phosphorylation of multiple downstream signaling molecules which are recruited to the receptor by direct binding or via adapter proteins. FGFRs are therefore considered to be one of the important drug targets for anticancer therapy. Amplification of FGFR1 is one of the crucial genetic alterations in squamous cell lung cancer and hormone receptor-positive breast cancer. Several FGFR-selective inhibitors are currently in clinical trials in order to treat patients with genetic alterations in FGFR. In addition, these FGFR kinase inhibitors generally share a common structural motif, which means that a common single mutation may confer resistance to these inhibitors. To address this issue, BOC Sciences is continuously searching for a novel inhibitor with a different chemical scaffold by developing its library of potential FGFR1 kinase inhibitors.

Figure 1. The fiblobrast growth factor structure and signaling network. (Yashiro, M.; Matsuoka, T. 2016)

Library Design

At BOC Sciences, our FGFR1 tyrosine targeted library is designed based on a set of different drug-like compounds from the BOC Sciences screening collection using a well-designed receptor-based method.

1. Firstly, the compounds are carefully filtered using an in-house medicinal chemistry filter such as PAINS and toxicant filters as well as the Rule of Five restrictions
2. Then, we apply the X-ray structures of known human FGFR1 kinase and select the protein-inhibitor complexes (with the inactive conformation of the kinase) from the PDB entry for in silico screening of BOC Sciences compounds collection
3. In this step, our experts characterize some key amino acids (Ala564, Glu571, Tyr563, Leu484, Phe489, Asp641, Leu630, Ile545, Phe642, Glu531, Val492, Glu562, Met535) to create a Unity query model of the protein binding site
4. At BOC Sciences, an advanced screening tool is used to prepare a database of ligands from a pre-selected diversity set of 50,000 from the BOC Sciences collection
5. Finally, the obtained hits will be further filtered and ranked based on QFit values. And the molecular docking is performed against selected compounds to identify the binding modes of the hits

Figure 2. Fiblobrast growth factor receptor-targeted therapeutics. (Yashiro, M.; Matsuoka, T. 2016)

Fibroblast Growth Factor Receptor 1 (FGFR1) Tyrosine Targeted Library Characteristics

• 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 Fibroblast Growth Factor Receptor 1 (FGFR1) Tyrosine Targeted Library design at competitive prices for global customers. Personalized and customized services of Fibroblast Growth Factor Receptor 1 (FGFR1) Tyrosine 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!