Covalent Kinase Screening Library | Kinase Focused Libraries - Individual Screening Sets | Kinase General Libraries

Kinase modulators currently constitute one of the primary focuses in drug discovery. Over 50 approved drugs have been categorized as protein kinase inhibitors, and numerous more are currently undergoing clinical trials [1]. Notably, in 2019 alone, the United States Food and Drug Administration (US FDA) approved four novel small-molecule protein kinase antagonists. Furthermore, it is noteworthy that within the past decade, there has been a remarkable proliferation in the diversity of chemotypes of protein kinase inhibitors [2]. The majority of these inhibitors are primarily employed in the context of targeted cancer therapy [3]. It should be emphasized that despite their predominant use in cancer therapy, certain kinase inhibitors have garnered approval for the treatment of a diverse array of other diseases, such as immunosuppression, inflammatory and autoimmune diseases, Alzheimer's disease, Parkinson's disease, and Gordon syndrome [4].

In the past decade, covalent targeting has seen a resurgence, particularly within the realm of protein kinase inhibitor development. Whatever the inherent complexities associated with covalent modifiers, the application of the targeted covalent inhibitors (TCIs) approach has yielded significant success in the quest for novel treatments. In fact, six covalent kinase inhibitors have received regulatory approval over the recent years, demonstrating considerable strides made in this field.

In this light, Life Chemicals presents its novel and carefully designed Covalent Kinase Screening Library of over 4,200 potential kinase covalent inhibitors represented by 10 diverse electrophilic warheads:

acrylamides
acrylates
aldehydes
bromoacetyl
maleimides

nitriles
terminal acrylates
alkenes
alkynes
thiols

The drug-like screening compounds were selected by molecular docking based on the proprietary collection of kinase-focused Screening Sets:

The specific screening libraries to which each compound belongs are indicated within the SD file.

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.

Further exploring our related products will make your search even more rewarding:

Figure 1. Covalent and Allosteric Protein Kinase sites and electrophilic Inhibitor warheads [6].

Representative screening compounds from the Kinase Covalent Screening Library

Reference:

Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors: A 2020 update. Pharmacol Res. 2020 Feb;152:104609.
Wells CI, Al-Ali H, Andrews DM, Asquith CRM, Axtman AD, Dikic I, Ebner D, Ettmayer P, Fischer C, Frederiksen M, Futrell RE, Gray NS, Hatch SB, Knapp S, Lücking U, Michaelides M, Mills CE, Müller S, Owen D, Picado A, Saikatendu KS, Schröder M, Stolz A, Tellechea M, Turunen BJ, Vilar S, Wang J, Zuercher WJ, Willson TM, Drewry DH. The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification. Int J Mol Sci. 2021 Jan 8;22(2):566.
Bhullar KS, Lagarón NO, Mcgowan EM, Parmar I, Jha A, Hubbard BP, et al. Kinase-targeted cancer therapies: progress, challenges, and future directions. Mol Cancer. 2018;17:48
Cohen, P., Cross, D. & Jänne, P.A. Kinase drug discovery 20 years after imatinib: progress and future directions. Nat Rev Drug Discov 20, 551–569 (2021). https://doi.org/10.1038/s41573-021-00195-4
Gehringer, M. (2020). Covalent Kinase Inhibitors: An Overview. In: Laufer, S. (eds) Proteinkinase Inhibitors. Topics in Medicinal Chemistry, vol 36. Springer, Cham. https://doi.org/10.1007/7355_2020_103
Xerxa E, Laufkötter O, Bajorath J. Systematic Analysis of Covalent and Allosteric Protein Kinase Inhibitors. Molecules. 2023 Aug 1;28(15):5805.