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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AZ 191

AZ191 is a potent small molecule inhibitor that selectively inhibits DYRK1B with IC50 of 17 nM; selective for DYRK1B over both DYRK1A and DYRK2.IC50 value: 17 nM [1]Target: DYRK1B inhibitorin vitro: Using in vitro kinase assays, phospho-specific immunoblot analysis and MS in conjunction with AZ191 we now show that DYRK1B phosphorylates CCND1 at Thr(286), not Thr(288), in vitro and in cells. In HEK (human embryonic kidney)-293 and PANC-1 cells (which exhibit DYRK1B amplification) DYRK1B drives Thr(286) phosphorylation and proteasome-dependent turnover of CCND1 and this is abolished by AZ191 or DYRK1B RNAi, but not by GSK3β inhibitors or GSK3β RNAi.

  • CAS Number: 1594092-37-1
  • MF: C24H27N7O
  • MW: 429.51700
  • Catalog: DYRK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c-Met-IN-2

c-Met-IN-2 is a potent, selective and orally available c-Met inhibitor, with an IC50 of 0.6 nM, with antitumor activity.

  • CAS Number: 1635406-73-3
  • MF: C24H21FN10O
  • MW: 484.49
  • Catalog: c-Met/HGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LOXO-101

Larotrectinib (LOXO-101) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).

  • CAS Number: 1223403-58-4
  • MF: C21H22F2N6O2
  • MW: 428.435
  • Catalog: Trk Receptor
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ON 146040

ON 146040 is a potent PI3Kα and PI3Kδ (IC50≈14 and 20 nM, respectively) inhibitor. ON 146040 also inhibits Abl1 (IC50<150 nM).

  • CAS Number: 1404231-34-0
  • MF: C24H23N7O3S
  • MW: 489.55
  • Catalog: Bcr-Abl
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ki20227

Ki-20227 is a highly selective c-Fms tyrosine kinase(CSF1R) inhibitor with IC50 value of 2 nM; 6 fold and > 100 fold selectivity over VEGFR2(IC50=12 nM) and c-Kit/PDGFRβ(IC50=451/217 nM), respectively.IC50 value: Target: CSF1Rin vitro: Ki20227 did not inhibit other kinases tested, such as fms-like tyrosine kinase-3, epidermal growth factor receptor, or c-Src (c-src proto-oncogene product). Ki20227 was also found to inhibit the M-CSF-dependent growth of M-NFS-60 cells but not the M-CSF-independent growth of A375 human melanoma cells in vitro [1]. Ki20227 inhibited M-CSF-dependent reactions, such as lipopolysaccharide-induced tumor necrosis factor-alpha production, which were enhanced by M-CSF in vitro [2]. in vivo: Ki20227 decreased the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats [1]. In addition, the number of CD11b(+), Gr-1(+), and Ly-6G(+) cells in the spleen decreased in the Ki20227-treated mice, and the CII-induced cytokine production in splenocytes isolated from the Ki20227-treated arthritic mice was also reduced [2]. Ki20227 treatments inhibited the turn-over/expansion of myeloid cells provoked by the immunization and subsequent MOG-specific T cell responses in our EAE animal model [3].

  • CAS Number: 623142-96-1
  • MF: C24H24N4O5S
  • MW: 480.536
  • Catalog: c-Fms
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 621.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 329.8±31.5 °C

Gefitinib D8

Gefitinib D8 (ZD1839 D8) is a deuterium labeled Gefitinib. Gefitinib is an EGFR tyrosine kinase inhibitor, with IC50 of 2-37 nM in NR6wtEGFR cells[1][2].

  • CAS Number: 857091-32-8
  • MF: C22H16D8ClFN4O3
  • MW: 454.95200
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Acetyl Gastric Inhibitory Peptide (human)

Acetyl Gastric Inhibitory Peptide (human) is a fatty acid derivatized analog of glucose-dependent insulinotropic polypeptide with improved antihyperglycaemic and insulinotropic properties. Acetyl Gastric Inhibitory Peptide (human) can be used for research of diabetes, insulin resistance and obesity[1][2][3].

  • CAS Number: 299898-33-2
  • MF: C228H340N60O67S
  • MW: 5025.60
  • Catalog: Insulin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-477736

PF 477736 is a potent, selective ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, 100-fold selectivity versus Chk2 (Ki, 47 nM).

  • CAS Number: 952021-60-2
  • MF: C22H25N7O2
  • MW: 419.480
  • Catalog: Aurora Kinase
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Damnacanthal

Damnacanthal is an anthraquinone isolated from the root of Morinda citrifolia. Damnacanthal is a highly potent, selective inhibitor of p56lck tyrosine kinase activity. Natural Damnacanthal inhibits p56 lck autophosphorylation and phosphorylation of exogenous substrates with IC50s of 46 nM and 220 nM, respectively. Damnacanthal is a potent inducer of apoptosis with anticancer activity. Damnacanthal also has antinociceptive, anti-inflammatory effects in mice and anti-fungal activity against Candida albicans[1][2][3][4].

  • CAS Number: 477-84-9
  • MF: C16H10O5
  • MW: 282.248
  • Catalog: Fungal
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 531.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 204.9±23.6 °C

AKN-028

AKN-028 is an orally active and potent FLT3 tyrosine kinase inhibitor (IC50 = 6 nM). AKN-028 causes dose-dependent inhibition of FLT3 autophosphorylation[1].

  • CAS Number: 1175017-90-9
  • MF: C17H14N6
  • MW: 302.33300
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AIM-100

AIM-100 is a small molecule inhibitor of Ack1 with an IC50 of 24 nM.IC50 value: 24 nM [3]Target: Ack1Ack1 inhibitor AIM-100 not only inhibited Ack1 activation but also suppressed AKT tyrosine phosphorylation, leading to cell cycle arrest in the G1 phase [1].The Ack1 inhibitor AIM-100 not only inhibited Ack1 activity but also was able to suppress AR Tyr(267) phosphorylation and its recruitment to the ATM enhancer. Notably, AIM-100 suppressed Ack1 mediated ATM expression and mitigated the growth of radioresistant CRPC tumors [2]. AIM-100, not only inhibited Ack1 activation but also able to suppress pTyr267-AR phosphorylation, binding of AR to PSA, NKX3.1, and TMPRSS2 promoters, and inhibit AR transcription activity [3].

  • CAS Number: 873305-35-2
  • MF: C23H21N3O2
  • MW: 371.43200
  • Catalog: Ack1
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sorafenib Tosylate

Sorafenib tosylate is a potent multikinase inhibitor, with IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.

  • CAS Number: 475207-59-1
  • MF: C28H24ClF3N4O6S
  • MW: 637.027
  • Catalog: Autophagy
  • Density: 1.454 g/cm3
  • Boiling Point: 523.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 270.3ºC

Succinyl phosphonate trisodium salt

Succinyl phosphonate trisodium salt (SP) is an α-ketoglutarate dehydrogenase (KGDHC) inhibitor, effective inhibits (KGDHC) in muscle, bacterial, brain, and cultured human fibroblasts[1][4].Succinyl phosphonate trisodium salt (SP) is an 2-Oxoglutarate dehydrogenase (OGDH) inhibitor, impairs viability of cancer cells in a cell-specific metabolism-dependent manner[2].Succinyl phosphonate trisodium salt (SP) inhibits the glutamate-induced ROS production in glutamate-stimulated hippocampal neurons in situ[3].

  • CAS Number: 864167-45-3
  • MF: C4H4Na3O6P
  • MW: 248.01
  • Catalog: ROS
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pexidartinib

Pexidartinib (PLX-3397) is a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 13 nM, 27 nM, and 11 nM for CSF1R, c-Kit, and FLT3, respectively.

  • CAS Number: 1029044-16-3
  • MF: C20H15ClF3N5
  • MW: 417.815
  • Catalog: c-Fms
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 580.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 304.6±30.1 °C

Onartuzumab

Onartuzumab (MetMAb) is a unique, humanized and affinity-matured monovalent (one-armed) monoclonal antibody against the MET receptor. Onartuzumab potently inhibits HGF binding and receptor phosphorylation and signaling. Onartuzumab has antibody-like pharmacokinetics and antitumor activity[1].

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

Btk inhibitor 2

Btk inhibitor 2 is a Bruton's tyrosine kinase (BTK) inhibitor extracted from patent US 20170224688 A1.

  • CAS Number: 1558036-85-3
  • MF: C24H25N5O3
  • MW: 431.49
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FLT3-IN-4

FLT3-IN-4 is a potent and orally effective Fms-like tyrosine receptor kinase 3 (FLT3; IC50=7 nM) inhibitor for treating acute myelogenous leukemia[1].

  • CAS Number: 2304799-09-3
  • MF: C23H25N7O2
  • MW: 431.49
  • Catalog: FLT3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RU-301

RU-301 is a pan-TAM receptor inhibitor, exerts pan-TAM inhibitory activity by binding at the interface between Gas6 and the Ig1 domain of the respective TAMs with Kd and IC50 values of 12 μM and 10 μM, respectively[1].

  • CAS Number: 1110873-99-8
  • MF: C21H19F3N4O4S
  • MW: 480.46
  • Catalog: TAM Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Foretinib (GSK1363089)

Foretinib is a multi-target tyrosine kinase inhibitor with IC50s of 0.4 nM and 0.9 nM for Met and KDR.

  • CAS Number: 849217-64-7
  • MF: C34H34F2N4O6
  • MW: 632.654
  • Catalog: c-Met/HGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 828.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 454.8±34.3 °C

PF-573228

PF-573228 is a potent and selective FAK inhibitor with IC50 of 4 nM for purified recombinant catalytic fragment of FAK.

  • CAS Number: 869288-64-2
  • MF: C22H20F3N5O3S
  • MW: 491.486
  • Catalog: FAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-00299804

Dacomitinib (PF-00299804) hydrate is an orally active, irreversible pan-ErbB inhibitor. Dacomitinib hydrate can be used in the research of cancers such as metastatic non-small cell lung cancer (NSCLC)[1].

  • CAS Number: 1042385-75-0
  • MF: C24H27ClFN5O3
  • MW: 487.95
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hu7691 free base

Hu7691 free base is an orally active, selective Akt inhibitor with IC50s of 4.0 nM, 97.5 nM, 28 nM for Akt1, Akt2 and Akt3, respectively. Hu7691 free base inhibits tumor growth and enables decrease of cutaneous toxicity in mice[1].

  • CAS Number: 2241232-43-7
  • MF: C22H21F3N4O
  • MW: 414.42
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AP26113

ALK-IN-1 is a potent and selective active inhibitor of anaplastic lymphoma kinase(ALK), Patent US20140066406 A1.

  • CAS Number: 1197958-12-5
  • MF: C26H34ClN6O2P
  • MW: 529.014
  • Catalog: ALK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 737.6±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 399.9±35.7 °C

Harmine hydrochloride

Harmine Hydrochloride (Telepathine Hydrochloride) is a natural dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) inhibitor with anticancer and anti-inflammatory activities. Harmine has a high affinity of 5-HT2A serotonin receptor, with an Ki of 397 nM[1].

  • CAS Number: 343-27-1
  • MF: C13H13ClN2O
  • MW: 248.708
  • Catalog: DYRK
  • Density: N/A
  • Boiling Point: 421.4ºC at 760mmHg
  • Melting Point: 265-270°C
  • Flash Point: 139.8ºC

Mifanertinib dimaleate

Mifanertinib dimaleate is a potent tyrosine kinase inhibitor with antineoplastic activity[1].

  • CAS Number: 1989592-50-8
  • MF: C29H27ClF3N5O10
  • MW: 698.00
  • Catalog: c-Met/HGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-56

EGFR-IN-56 (Compound 13a) is a potent EGFR inhibitor with IC50 values of 541.7 nM and 132.1 nM against EGFRT790M and EGFRT790M/L858R, respectively. EGFR-IN-56 blocks cancer cells in G2/M phase and induce into late apoptosis[1].

  • CAS Number: 2477726-83-1
  • MF: C23H22N4O3S
  • MW: 434.51
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Batatasin III

Batatasin III, a stilbenoid, inhibits cancer migration and invasion by suppressing epithelial to mesenchymal transition (EMT) and FAK-AKT Signals. Batatasin III has anti-cancer activities[1].

  • CAS Number: 56684-87-8
  • MF: C16H18O3
  • MW: 258.31200
  • Catalog: Akt
  • Density: 1.126g/cm3
  • Boiling Point: 406.1ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 199.4ºC

8-CPT-Cyclic AMP sodium

8-CPT-Cyclic AMP (8-CPT-cAMP) sodium is a selective activator of cyclic AMP-dependent protein kinase (PKA). 8-CPT-Cyclic AMP sodium is also a potent inhibitor of the cyclic GMP-specific phosphodiesterase (PDE VA) with an IC50 of 0.9 μM. 8-CPT-Cyclic AMP sodium also inhibits PDE III and PDE IV with IC50Epac and is a potent Epac activator[1][2].

  • CAS Number: 93882-12-3
  • MF: C16H14ClN5NaO6PS
  • MW: 493.79
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: 799.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 437.1ºC

BLU0588

BLU0588 is an orally active, potent and selective PRKACA (protein kinase cAMP-activated catalytic subunit alpha) kinase inhibitor, with an IC50 of 1 nM and dissociation constant (Kd) of 4 nM. BLU0588 can be used for fibrolamellar carcinoma (FLC) research[1].

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

IHMT-TRK-284

IHMT-TRK-284 (Compound 34) is a potent, orally active type II TRK kinase inhibitor with IC50 values of 10.5, 0.7, and 2.6 nM to TRKA, B, and C respectively. IHMT-TRK-284 displays great selectivity profile in the kinome and good in vivo antitumor efficacies[1].

  • CAS Number: 2416844-79-4
  • MF: C25H27N7OS
  • MW: 473.59
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A