Kinase Focused Library

Protein kinases are among the most promising drug targets for anticancer drug development [1-3]. There are numerous protein kinases encoded in the human genome [1]. While there are many reported kinase modulators, most of them possess similar structures and selectivity issues [4].

Status of therapeutic development for driver kinases

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).

Life Chemicals presents its Protein Kinase Focused Library of around 32,000 drug-like screening compounds selected by a ligand-based approach.

First, a reference set of over 135,000 compounds with reported kinase inhibitory activity extracted from the ChEMBL database was prepared (IC50, Ki, etc., less than 10 μM, Inhibition > 50 %). Then the Life Chemicals HTS Compound Collection was analyzed using a 2D fingerprint similarity search approach (Tanimoto > 0.85) against the reference set of modulators of protein kinase activity. Finally, the resulting screening compounds were filtered by in-house MedChem filters to remove PAINS, toxicophore and reactive moieties.

Compound cherry-picking is available. Custom compound selection based on specific parameters can be performed on request.
Please, contact us at orders@lifechemicals.com for any details and quotations.

 

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

The Screening Library contains analogs of kinase inhibitors against the following molecular targets:

  • 3-phosphoinositide dependent protein kinase-1
  • 6-phospho-1-fructokinase
  • 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
  • Adenosine kinase
  • Autoinducer 1 sensor kinase/phosphatase luxN
  • Bcr/Abl fusion protein
  • CAI-1 autoinducer sensor kinase/phosphatase CqsS
  • Calcium-dependent protein kinase (1, 4)
  • CaM kinase (I alpha, II delta, IV, alpha, beta)
  • cAMP-dependent protein kinase alpha
  • Casein kinase (I alpha, delta, epsilon, gamma, II)
  • CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase)
  • CDK-interacting protein 1
  • Cdk-related protein kinase 6
  • Cell division cycle 7-related protein kinase
  • Cell division protein kinase 8
  • c-Jun N-terminal kinase (1, 2, 3)
  • Connector enhancer of kinase suppressor of ras 1
  • Cyclin-dependent kinase (1, 1/cyclin B, 1/cyclin B1, 2, 2/cyclin A, 2/cyclin E, 2/cyclin E1, 4, 4/cyclin D, 4/cyclin D1, 5, 5/CDK5 activator 1, 6, 7, 7/ cyclin H, 9)
  • Death-associated protein kinase (1, 3)
  • Discoidin domain-containing receptor 2
  • DNA-dependent protein kinase
  • Dual specificity mitogen-activated protein kinase (1, 2)
  • Dual specificity protein kinase (CLK1, CLK4, TTK)
  • Dual specificity tyrosine-phosphorylation-regulated kinase (1A, 1B, 2)
  • Enteropeptidase
  • Ephrin type-A receptor (2, 4)
  • Ephrin type-B receptor (3, 4)
  • Epidermal growth factor receptor ErbB1 and ErbB2 Epithelial discoidin domain-containing receptor 1
  • Eukaryotic translation initiation factor 2-alpha kinase 3
  • Fibroblast growth factor receptor (1, 2, 3)
  • Focal adhesion kinase 1
  • G protein-coupled receptor kinase 6
  • Glycogen synthase kinase (3 alpha, beta)
  • G-protein coupled receptor kinase 2
  • Hepatocyte growth factor receptor
  • Hexokinase type IV
  • Histidine kinase
  • Homeodomain-interacting protein kinase 2
  • Inhibitor of nuclear factor kappa B kinase (beta, epsilon)
  • Insulin-like growth factor I receptor
  • Interleukin-1 receptor-associated kinase 4
  • KinA/Spo0F (sporulation kinase A/sporulation initiation phosphotransferase F)
  • Leucine-rich repeat ser/threonine-protein kinase 2
  • LIM domain kinase (1, 2)
  • Macrophage-stimulating factor receptor kinase
  • MAP kinase (ERK1, ERK2, p38-alpha, beta, delta)
  • MAP kinase signal-integrating kinase 2
  • MAP kinase-activated protein kinase 2
  • MAP kinase-interacting ser/threonine-protein kinase MNK1
  • MAP/microtubule affinity-regulating kinase 2
  • Maternal embryonic leucine zipper kinase
  • Mitogen-activated protein kinase (4, 5, 7, 8, 14)
  • Myosin light chain kinase, smooth muscle
  • Nerve growth factor receptor Trk-A
  • Pantothenate kinase 3
  • PAS domain-containing ser/threonine-protein kinase
  • Phosphatidylinositol 4,5-bisphosphate 3-kinase Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing subunit gamma
  • Phosphatidylinositol-5-phosphate 4-kinase type-2 (alpha, gamma)
  • Phosphoglycerate kinase
  • PI3-kinase p110 (alpha, beta, delta, gamma subunits)
  • PI4-kinase (alpha, beta subunits)
  • Platelet-derived growth factor receptor (alpha, beta)
  • Protein arginine N-methyltransferase 5
  • Protein kinase 6
  • Protein kinase C (alpha, eta, iota, mu, theta, zeta)
  • Protein kinase Pfmrk
  • Protein tyrosine kinase 2 beta
  • Proto-oncogene tyrosine-protein kinase MER
  • Putative hexokinase HKDC1
  • Putative uncharacterized protein pk7
  • Pyridoxal kinase
  • Pyruvate dehydrogenase kinase (1, 2, 3)
  • Pyruvate kinase
  • Pyruvate kinase isozymes M1/M2
  • RAC-alpha serine/threonine-protein kinase
  • Receptor protein-tyrosine kinase erbB-2
  • Receptor-interacting ser/threonine-protein kinase 1
  • Rho-associated protein kinase (1, 2)
  • Ribosomal protein S6 kinase (1, alpha 2, alpha 3, alpha 5)
  • Serine/threonine-protein kinase (17B, 33, AKT, AKT2, Aurora-A, Aurora-B, B-raf, Chk1, Chk2, c-TAK1, EEF2K, ILK-1, MRCK-A, mTOR, PAK 1, PAK 4, PIM1, PIM2, PIM3, pknB, PLK1, PLK2, PLK3, PLK4, RAF, R3, Sgk1, ATM, TAO1, TAO2, TAO3)
  • Serine/threonine-protein kinase/endoribonuclease IRE1
  • Sphingosine kinase (1, 2)
  • Streptokinase A
  • Testis-specific serine/threonine-protein kinase 1
  • TGF-beta receptor type (I, II)
  • TRAF2- and NCK-interacting kinase
  • Transient receptor potential cation channel subfamily M member 7
  • Tyrosine kinase non-receptor protein 2
  • Tyrosine-protein kinase (ABL, ALK, BRK, BTK, FES, FYN, ITK/TSK, JAK1, JAK2, JAK3, LCK, Lyn, FLT3, RET,
  • UFO, SRC, SYK, TIE-2, TYK2, YES)
  • Uridine-cytidine kinase 2
  • Urokinase-type plasminogen activator
  • Vascular endothelial growth factor receptor (1, 2)

Reserences:

  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).
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