Kinase Focused Libraries

Protein kinases are essential regulators in numerous diseases, making them one of the most important drug targets of the 21st century. They are the second most studied target group after G-protein-coupled receptors (GPCRs). There are 80 FDA-approved kinase inhibitors of approximately two dozen different kinases as of 2024, including seven new approvals in 2023 alone [1]. Kinase inhibitors are especially promising in the field of anticancer drug development, leveraging the extensive presence of kinase-encoding genes in the human genome [1–3]. However, many reported kinase modulators face challenges related to structural similarities and selectivity, highlighting the need for more precise and innovative approaches in kinase-targeted drug discovery [4].

Our cheminformatics team prepared an extensive selection of over 67,000 drug-like screening compounds that are predicted to function as small-molecule kinase inhibitors. These novel in-house synthesized molecules have been scrupulously selected from our proprietary HTS Compound Collection using advanced computer-aided ligand-based approaches.

To meet a broad spectrum of diverse research needs, we have developed a comprehensive Screening Library that includes both general and specialized Kinase-focused Screening Sets designed as a powerful tool for kinase-targeted high-throughput screening projects across various drug discovery areas:

• Covalent Kinase Screening Library
• Allosteric Kinase Screening Compound Library
• Kinase Screening Library (KSL)
• Protein Kinase Diversity Set 
• Tyrosine Kinase Screening Library
• Dark Kinome Screening Library

Our collection of assay-ready kinase-related screening sets

• Pre-plated Kinase Screening Library: 3,200 drug-like screening compounds, selected using pharmacophore models and Markush structure frameworks derived from established kinase inhibitors
• Pre-plated Kinase Diversity Screening Set: 2,000 potential protein and lipid kinase inhibitors, featuring optimal physicochemical properties and maximal diversity
• Pre-plated G Protein-coupled Receptor Kinase Screening Set: 925 drug-like screening compounds with predicted inhibitory activity against GRKs

The compound selection can be customized based on your requirements, cherry picking is available.

Please, contact us at orders@lifechemicals.com for any additional information and price quotations.

Representative screening compounds from the Kinase Focused Library by Similarity Search:

F6788-9363

F0037-0136

F0593-0066

F2173-0854

F0700-0009

F0675-0284

F6548-1146

F2670-0345

F2573-0368

F2704-0118

F3411-2803

F0916-3927

F3348-0458

F3168-0902

F1602-0662

F1604-0233

F1183-0149

F0372-0287

Compound selection

Our cheminformatics team first compiled a reference set of over 135,000 compounds with reported kinase inhibitory activity (e.g., IC₅₀, K_i < 10 μM; Inhibition > 50 %) from the ChEMBL database. This was followed by a 2D fingerprint similarity search (Tanimoto coefficient > 0.85) of the Life Chemicals HTS Compound Collection against this reference set of protein kinase modulators. The resulting screening compounds were then thoroughly filtered using in-house medicinal chemistry criteria to eliminate PAINS, toxicophores, and reactive moieties, ensuring a high-quality selection.

Several dedicated compound subsets were then prepared by means of advanced cheminformatic approaches to support specific kinase-focused drug discovery projects:

1. Covalent Kinase Screening Library: this subset comprises over 3,100 potential covalent kinase inhibitors possessing at least one of 10 diverse electrophilic warheads
2. Allosteric Kinase Screening Compound Library: focusing on allosteric modulation, this library includes almost 1,000 potential inhibitors and modulators targeting four types of allosteric kinase sites
3. Kinase Screening Library (KSL): developed through the application of pharmacophore models, Markush structures, and similarity searches, KSL offers 3,200 drug-like screening compounds
4. Protein Kinase Diversity Set: by narrowing down our collection based on structural diversity, this set provides 3,200  predicted small-molecule kinase inhibitors with optimal physicochemical properties
5. Tyrosine Kinase Screening Library: this subset includes more than 5,600 potential specific inhibitors of tyrosine kinases, which are crucial targets in cancer therapy
6. Dark Kinome Screening Library: designed to target understudied "dark kinases," this library offers 1,400 drug-like screening compounds to explore these less-characterized promising drug targets

 

Fig. 1. Status of therapeutic development for driver kinases according to Fleuren, E., Zhang, L., Wu, J. et al. The kinome 'at large' in cancer. Nat Rev Cancer 16, 83–98 (2016).

Fig. 2. Compound distribution against single protein targets within the Protein Kinase Focused Library.

References:

1. Fleuren, E., Zhang, L., Wu, J. et al. The kinome 'at large' in cancer. Nat Rev Cancer 16, 83–98 (2016).
2. Knapp, S. New opportunities for kinase drug repurposing and target discovery. Br J Cancer 118, 936–937 (2018).
3. Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update. Pharmacol Res. Feb;152:104609 (2020).
4. Breen, Meghan E, and Matthew B Soellner. Small molecule substrate phosphorylation site inhibitors of protein kinases: approaches and challenges. ACS chemical biology 10,1 : 175-89 (2015).