Protein-tyrosine kinases (PTKs) catalyze the transfer of the γ-phosphate of ATP to tyrosine residues of protein substrates, are critical components of signaling pathways that control cellular proliferation and differentiation. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs.

The RTK family includes the receptors for insulin and for many growth factors, such as EGF, FGF, PDGF, VEGF, and NGF. RTKs are transmembrane glycoproteins that are activated by the binding of their ligands, and they transduce the extracellular signal to the cytoplasm by phosphorylating tyrosine residues on the receptors themselves (autophosphorylation) and on downstream signaling proteins. RTKs activate numerous signaling pathways within cells, leading to cell proliferation, differentiation, migration, or metabolic changes. In addition, nonreceptor tyrosine kinases (NRTKs), which include Src, JAKs, and Abl, among others, are integral components of the signaling cascades triggered by RTKs and by other cell surface receptors such as GPCRs and receptors of the immune system. NRTKs are critical components in the regulation of the immune system.

RTKs and NRTKs have been implicated in the progression of diseases such as cancer, diabetic retinopathy, atherosclerosis, and psoriasis. Protein kinases, including RTKs, are one of the most frequently mutated gene families implicated in cancer, which has prompted numerous studies on their role in cancer pathogenesis. There are four main mechanisms of RTK dysregulation in human cancers: genomic rearrangements, autocrine activation, overexpression and gain- or loss-of-function mutations. Currently, there are several clinically available small molecule inhibitors and monoclonal antibodies against specific RTKs.

References:
[1] Hubbard SR, et al. Annu Rev Biochem. 2000;69:373-98.
[2] Robinson DR, et al. Oncogene. 2000 Nov 20;19(49):5548-57.
[3] McDonell LM, et al. Hum Mol Genet. 2015 Oct 15;24(R1):R60-6.


Anti-infection >
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Antibody-drug Conjugate >
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Autophagy >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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Metabolic Enzyme/Protease >
15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
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NF-κB >
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BT5528

BT5528 is a bicyclic peptide toxin conjugate, an EphA2 activator. BT5528, made up of a bicyclic peptide and Auristatin E (HY-15582), is derivated from BCY6099. BT5528 shows potent anti-tumor activity without bleeding or coagulation toxicity in rats model[1][2].

  • CAS Number: 2648849-70-9
  • MF: C201H315N53O52S3
  • MW: 4403.14
  • Catalog: Ephrin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JTE-952

JTE-952 is a potent, oral active and selective Type II inhibitor of colony stimulating factor-1 receptor (CSF-1R or cFMS, type III receptor tyrosine kinase), with IC50 values of 13 nM and 261 nM for CSF1R and TrkA , respectively. Effective against a mouse collagen-induced model of arthritis[1].

  • CAS Number: 1255303-54-8
  • MF: C30H34N2O6
  • MW: 518.60
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hypothemycin

Hypothemycin, a fungal polyketide, is a multikinase inhibitor with Kis of 10/70 nM, 17/38 nM, 90 nM, 900 nM/1.5 μM, and 8.4/2.4 μM for VEGFR2/VEGFR1, MEK1/MEK2, FLT-3, PDGFRβ/PDGFRα, and ERK1/ERK2, respectively[1][2].

  • CAS Number: 76958-67-3
  • MF: C19H22O8
  • MW: 378.37300
  • Catalog: ERK
  • Density: 1.343g/cm3
  • Boiling Point: 673.1ºC at 760 mmHg
  • Melting Point: 170-172℃
  • Flash Point: 242.7ºC

Itacnosertib

Itacnosertib (TP-0184) is both inhibitor to JAK2, ACVR1 (ALK2) and ALK5 as described in WO2014151871[1].

  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 675.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.2±34.3 °C

Afatinib impurity 11

Afatinib impurity 11 is an impurity of Afatinib. Afatinib is an irreversible EGFR family inhibitor with IC50s of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively[1].

  • CAS Number: 1402086-20-7
  • MF: C21H18ClFN4O3
  • MW: 428.84
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Leucettinib-92

Leucettinib-92 (compound 92) is an inhibitor of DYRK/CLK kinase, The IC50s are 147 nM (CLK1), 39 nM (CLK2), 5.2 nM (CLK4), 0.8 μM (CLK3), 124 nM (DYRK1A), 204 nM (DYRK1B), 0.16 μM (DYRK2), respectively. 1.0 μM (DYRK3), 0.52 μM (DYRK4), 2.78 μM (GSK3)[1].

  • CAS Number: 2732859-57-1
  • MF: C21H22N4OS
  • MW: 378.49
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC-S 7003

Lck Inhibitor is a new class of compounds that are potent inhibitors of Lck with an IC50 value of 7 nM.IC50 Value: 7 nM [1]Target: Lckin vitro: Lck Inhibitor (compound 25) exhibited good potency in the T-cell receptor-induced IL-2 secretion assay (IL- 2) and also inhibited subsequent T-cell proliferation (T-cell prolif.) in the same human T -cells.in vivo: A once daily dose of 25was administered orally at 10, 30, and 60 mg/kg from day 9 today 17. Paw volume was measured daily from day 9 through day 18. The compound showed a dose-dependent inhibition of arthritis, with an ED50 estimated at 24 mg/kg (Figure 6). Based on the measured plasma levels from the three dose groups, the exposure of 25 at the ED50 was estimated to be 2.7 μM·h (Cmax≈ 0.7 μM) [1].Clinical trial: N/A

  • CAS Number: 847950-09-8
  • MF: C31H30N8O
  • MW: 530.62300
  • Catalog: Src
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CPD-1224

CPD-1224 is an orally active derivative of ALK inhibitors to cereblon ligands. CPD-1224 targets to EML4-ALK oncogenic fusions, and degrades ALK and mutant L1196M/G1202R[1].

  • CAS Number: 2891620-68-9
  • MF: C43H47ClN8O7S
  • MW: 855.40
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BCR-ABL-IN-3

BCR-ABL-IN-3 is a potent and irreversible Bcr-Abl inhibitor with an IC50 of ≤100 nM for Ba/F3Bcr-AblT3151. BCR-ABL-IN-3 has anti-cancer activity[1].

  • CAS Number: 2240191-12-0
  • MF: C20H17ClF2N4O3S
  • MW: 466.89
  • Catalog: Bcr-Abl
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Annh31

AnnH31 is a potent Inhibitor of DYRK1A Kinase.

  • CAS Number: 241809-12-1
  • MF: C15H13N3O
  • MW: 251.28
  • Catalog: Monoamine Oxidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2801653

Merestinib (LY2801653) is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM.

  • CAS Number: 1206799-15-6
  • MF: C30H22F2N6O3
  • MW: 552.531
  • Catalog: c-Met/HGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 795.3±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 434.8±32.9 °C

PROTAC IRAK4 degrader-5

PROTAC IRAK4 degrader-5 is a PROTAC-based IRAK4 degrader extracted from patent US20190192668A1, compound I-171[1].

  • CAS Number: 2360530-61-4
  • MF: C41H40F3N11O9
  • MW: 887.82
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BLZ945

BLZ945 is a potent, selective and brain-penetrant CSF-1R inhibitor with an IC50 of 1 nM, showing more than 1,000-fold selectivity against its closest receptor tyrosine kinase homologs.

  • CAS Number: 953769-46-5
  • MF: C20H22N4O3S
  • MW: 398.479
  • Catalog: c-Fms
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CH7233163

CH7233163 is a noncovalent ATP-competitive inhibitor for EGFR-Del19/T790M/C797S. CH7233163 can overcome Osimertinib (HY-15772)-Resistant EGFR-Del19/T790M/C797S mutation. CH7233163 blocks the EGFR phosphorylation in the Del19/T790M/C797S_NIH3T3 cells. CH7233163 has antitumor activities[1].

  • CAS Number: 2923365-71-1
  • MF: C31H34F3N9O3S
  • MW: 669.72
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Daphnetin

Daphnetin (7,8-dihydroxycoumarin), one coumarin derivative isolated from plants of the Genus Daphne, is a protein kinase inhibitor, with IC50s of 7.67 μM, 9.33 μM and 25.01 μM for EGFR, PKA and PKC in vitro, respectively[1][2]. Daphnetin (7,8-dihydroxycoumarin) is a secondary metabolite of plants used in folk medicine to counter inflammatory and allergic diseases, also has been clinically used in the treatment of coagulation disorders, rheumatoid arthritis with anti-malarian and anti-pyretic properties[3].

  • CAS Number: 486-35-1
  • MF: C9H6O4
  • MW: 178.14
  • Catalog: PKC
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 430.4±45.0 °C at 760 mmHg
  • Melting Point: 265-268°C (dec.)
  • Flash Point: 184.5±22.2 °C

TIE-2/VEGFR-2 kinase-IN-2

TIE-2/VEGFR-2 kinase-IN-2 is a potent dual VEGFR2 and Tie-2 inhibitor with pIC50 values of 8.61 and 8.56, respectively[1]. TIE-2/VEGFR-2 kinase-IN-2 is an anti-angiogenic agent and can be used for cancer research[2].

  • CAS Number: 501693-48-7
  • MF: C20H13F4N5O2
  • MW: 431.34
  • Catalog: VEGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNF-4877

GNF4877 is a potent DYRK1A and GSK3β inhibitor with IC50s of 6 nM and 16 nM, respectively, which leads to blockade of nuclear factor of activated T-cells (NFATc) nuclear export and increased β-cell proliferation (EC50 of 0.66 μM for mouse β (R7T1) cells)[1].

  • CAS Number: 2041073-22-5
  • MF: C25H27FN6O4
  • MW: 494.52
  • Catalog: GSK-3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DCC-2618

Ripretinib (DCC-2618) is a pan-KIT and PDGFRA inhibitor, and has antitumor activity.

  • CAS Number: 1442472-39-0
  • MF: C24H21BrFN5O2
  • MW: 510.36
  • Catalog: c-Kit
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gefitinib-based PROTAC 3

Gefitinib-based PROTAC 3, conjugating an EGFR binding element to a VHL ligand via a linker, induces EGFR degradation with DC50s of 11.7 nM and 22.3 nM in HCC827(exon 19 del) and H3255 (L858R mutantion) cells, respectively[1].

  • CAS Number: 2230821-27-7
  • MF: C47H57ClFN7O8S
  • MW: 934.51
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dosimertinib

Dosimertinib is a highly potent, selective, and orally efficacious deuterated EGFR targeting clinical candidate for the treatment of non-small-cell lung cancer.

  • CAS Number: 2403760-70-1
  • MF: C28H28D5N7O2
  • MW: 504.64
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/HER2-IN-3

EGFR/HER2-IN-3 (Compound ZINC21942954) is a dual inhibitor of EGFR and HER2[1].

  • CAS Number: 1031620-09-3
  • MF: C26H23N5O3
  • MW: 453.49
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WY-135

WY-135 is a ALK (IC50=1.4 nM) and ROS1 (IC50=1.1 nM) dual inhibitor.

  • CAS Number: 2163060-83-9
  • MF: C28H34ClN9O3S
  • MW: 612.15
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bucladesine (calcium salt)

Bucladesine calcium salt(DC2797 calcium salt) is a membrane permeable selective activator of PKA.Target: PKABucladesine (bilateral infusion of 10 mM or 100 mM) leads to a significant reduction in escape latency and travel distance (showing an improvement in spatial memory) compared to the control, as assesed by Morris water maze task in male rats. Bucladesine at 1 mM and 5 mM concentrations infused within minutes after 0.5 mg nicotine infusion improves spatial memory retention in male rats [1]. Bucladesine (10 mM/side) combined with Nicotine (0.5 mM/side) results in a significant increase in the ChAT and VAChT immunoreactivity in CA1 regions, and increase in the optical density and amount of ChAT and VAChT immunostaining correlates with the decrease in escape latency and traveled distance in rats treated with Nicotine and low dose of Bucladesine [2]. Bucladesine is absorbed very rapidly and almost completely when the aqueous solution is applied to the site where the skin has been excised. Bucladesine is absorbed rapidly but slower than in the full-thickness abrasion rat model in the case of stripped skin [3]. Bucladesine (single or multiple administration of an emulsion containing 1.5%) is capable of significantly reducing the inflammatory oedema in the arachidonic acid induced ear oedema model in mice [4].

  • CAS Number: 938448-87-4
  • MF: C18H23Ca0.5N5O8P
  • MW: 488.42
  • Catalog: PKA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Regorafenib

Regorafenib (BAY 73-4506) mesylate is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC50 values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib mesylate shows very robust antitumor and antiangiogenic activity[1].

  • CAS Number: 835621-08-4
  • MF: C22H19ClF4N4O6S
  • MW: 578.92100
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FAK-IN-5

FAK-IN-5 (Compound 8l) is a FAK signaling inhibitor. FAK-IN-5 induces cell apoptosis and autophagy[1].

  • CAS Number: 2408317-70-2
  • MF: C29H29ClF3N3O4
  • MW: 576.01
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gefitinib N-oxide

Gefitinib N-oxide is the N-oxide derivative of Gefitinib. Gefitinib is an EGFR tyrosine kinase inhibitor, with IC50 of 2-37 nM in NR6wtEGFR cells[1][2].

  • CAS Number: 847949-51-3
  • MF: C22H24ClFN4O4
  • MW: 462.90200
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-1

JAK3/BTK-IN-1 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-1 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147952A1, compound 002)[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c-Fms-IN-13

c-Fms-IN-13 (compound 14) is a potent FMS kinase inhibitor with an IC50 value of 17 nM. c-Fms-IN-13 can be used as an anti-inflammatory agent[1].

  • CAS Number: 885704-58-5
  • MF: C22H26N4O2
  • MW: 378.47
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AD57

AD57 is an orally active multikinase inhibitor, inhibits RET, BRAF, S6K and Src, with greatly reduces mTOR activity[1].

  • CAS Number: 1093380-42-7
  • MF: C22H20F3N7O
  • MW: 455.44
  • Catalog: Raf
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-21

EGFR-IN-21 is a potent EGFR inhibtior with an IC50 of 0.38 nM. EGFR-IN-21 has antitumor activity[1].

  • CAS Number: 2648206-31-7
  • MF: C36H44BrN10O2P
  • MW: 759.68
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A