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.


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ONO4059 hydrochloride

Tirabrutinib (ONO-4059) hydrochloride is a selective and novel inhibitor of BTK with IC50 2.2 nm, Tirabrutinib binds to BTK within B cells, thereby preventing B-cell receptor signaling and impeding B-cell development.

  • CAS Number: 1439901-97-9
  • MF: C25H23ClN6O3
  • MW: 490.941
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LM22A-4

LM22A-4 is a specific agonist of tyrosine kinase receptor B, used for neurological disease research.

  • CAS Number: 37988-18-4
  • MF: C15H21N3O6
  • MW: 339.34400
  • Catalog: Trk Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Famitinib (SHR1020)

Famitinib (SHR1020), an orally active multi-targeted kinase inhibitor, inhibits the activity of c-kit, VEGFR-2 and PDGFRβ with IC50 values of 2.3 nM, 4.7 nM and 6.6 nM, respectively[1]. Famitinib exerts powerful antitumor activity in human gastric cancer cells and xenografts.Famitinib triggers apoptosis[2].

  • CAS Number: 1044040-56-3
  • MF: C23H27FN4O2
  • MW: 410.48
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 677.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 363.3±31.5 °C

SRX3207

SRX3207 is an orally active and first-in-class dual Syk/PI3K inhibitor. SRX3207 possesses anti-tumor activity[1].

  • CAS Number: 2254693-15-5
  • MF: C29H29N7O3S
  • MW: 555.65
  • Catalog: PI3K
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PP121

PP121 is a multi-targeted kinase inhibitor with IC50s of 10, 60, 12, 14, 2 nM for mTOR, DNK-PK, VEGFR2, Src, PDGFR, respectively.

  • Density: 1.63
  • Boiling Point: 650.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 347.4±30.1 °C

[Tyr0] Gastric Inhibitory Peptide (23-42), human

[Tyr0] Gastric Inhibitory Peptide (23-42), human, a glucose-dependent insulinotropic polypeptide (GIP), is a weak inhibitor of gastric acid secretion that also stimulates insulin secretion. [Tyr0] Gastric Inhibitory Peptide (23-42), human can be used in diabetes, obesity research[1][2].

  • CAS Number: 121765-67-1
  • MF: C119H182N34O31
  • MW: 2584.93
  • Catalog: Insulin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JK-P3

JK-P3 is a potent and pan VEGFR2 inhibitor, with IC50s of 7.83 μM, 27 μM and 5.18 μM for VEGFR2, FGFR1 and FGFR3, respectively. JK-P3 can inhibit VEGF-A-stimulated VEGFR2 activation and intracellular signalling, also inhibits endothelial monolayer wound closure and angiogenesis, as well as fibroblast growth factor receptor kinase activity in vitro. JK-P3 has anti-angiogenic activity[1].

  • CAS Number: 942655-44-9
  • MF: C18H17N3O3
  • MW: 323.35
  • Catalog: FGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 499.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 255.9±28.7 °C

HG-14-10-04

HG-14-10-04 is a potent and specific ALK inhibitor with IC50 of 20 nM.IC50 value: 20 nMTarget: ALKMore information can be found in the following Patent, Example 10Preparation of substituted pyrimidinamines as ALK kinase inhibitorsBy Aquila, Brian; Kamhi, Victor; Peng, Bo; Pontz, Timothy; Saeh, Jamal Carlos; Thakur, Kumar; Yang, Bin From U.S. Pat. Appl. Publ. (2012), US 20120028924 A1 20120202.

  • CAS Number: 1356962-34-9
  • MF: C29H34ClN7O
  • MW: 532.08000
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD3229 Tosylate

AZD3229 Tosylate is a potent pan-KIT mutant inhibitor for the treatment of gastrointestinal stromal tumors.

  • CAS Number: 2248003-71-4
  • MF: C31H34FN7O6S
  • MW: 651.71
  • Catalog: c-Kit
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pexidartinib hydrochloride (PLX-3397)

Pexidartinib hydrochloride (PLX-3397 hydrochloride) is a potent, selective and ATP-competitive CSF1R (cFMS) and c-Kit inhibitor, with IC50s of 20 and 10 nM, respectively. Pexidartinib exhibits 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases, such as FLT3, KDR (VEGFR2), LCK, FLT1 (VEGFR1) and NTRK3 (TRKC), with IC50s of 160, 350, 860, 880, and 890 nM, respectively[1].

  • CAS Number: 2040295-03-0
  • MF: C20H16Cl2F3N5
  • MW: 454.28
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NT157

NT157is a selective inhibitor of IRS-1/2, IC50 values at sub-micromolar doses (ranging from 0.3 to 0.8 μM) .IC50 value: 0.3 to 0.8 μM [1]Target: Insulin receptorin vitro: NT157 significantly affects the cells' migratory ability, as confirmed by a wound-healing assay. NT157 induces cytostatic effects, as evidenced by G2/M cell cycle arrest, and does not affect apoptosis. NT157, a novel small-molecule that specifically targets IRS protein, in OS cells. NT157 is a small-molecule inhibitor that induces Ser-phosphorylation and consequently the degradation of IRS-1 and IRS-2. NT157 efficiently affects migration ability of MG-63 and U-2OS OS cells. NT157 treatment induces cell cycle arrest and inhibits IGF system signaling. [1] The density of LNCaP cells grown in FBS was decreased approximately 20% at 1 μM, approximately 70% at 2 μM, and >90% at 5 μM (IC50, 1.4 μM). Growth of LNCaP cells is suppressed >60% when cultured in CSS but still exhibited significant density at 2 μM and maximal decreased density at 5 μM. The density of FBS-cultured PC3 cells was similarly decreased by NT157 treatment (40% at 2 μM and > 70% at 5 μM; IC50, 2.5 μM). [2]in vivo: NT157 suppresses growth of LNCaP xenografts following castration. NT157 treatment affects IGF1R and IRS targets in xenografts and significantly delays castration-resistant progression of LNCaP androgen-responsive xenografts when combined with castration. NT157 potentiates docetaxel activity in PC3 xenografts.[2]

  • CAS Number: 1384426-12-3
  • MF: C16H14BrNO5S
  • MW: 412.255
  • Catalog: Insulin Receptor
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 660.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 353.1±34.3 °C

CA-4948

CA-4948 is a potent, selective and orally bioavailable IRAK4 kinase inhibitor with an IC50 of < 50 nM. CA-4948 can be used for the treatment of lymphoma[1].

  • CAS Number: 1801344-14-8
  • MF: C24H25N7O5
  • MW: 491.50
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EVT801

EVT801 is an orally active and selective inhibitor of VEGFR-3 (IC50=11 nM), which has antitumor effects. EVT801 inhibits not only VEGF-C-induced human endothelial cell proliferation, but also tumor (lymphatic) angiogenesis in tumor mouse models. EVT801 can reduce tumor hypoxia, immunosuppressive cytokines (CCL4, CCL5) and myeloid derived suppressor cells (MDSC) production. EVT801 has synergistic effect with immune checkpoint therapy (ICT), which improves ICT response rate and has better inhibitory effect on cancer mouse models[1].

  • CAS Number: 1412453-70-3
  • MF: C19H21N5O3
  • MW: 367.40
  • Catalog: ERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALK-IN-22

ALK-IN-22 (compound I-24) is a potent ALK inhibitor with IC50 values of 2.3, 3.7 and 2.9 nM for ALK, ALKL1196M and ALKG1202R, respectively. ALK-IN-22 down-regulated the phosphorylation of ALK and its downstream proteins. ALK-IN-22 induces apoptosis. ALK-IN-22 can be used for tumor research[1].

  • CAS Number: 2468219-09-0
  • MF: C24H24ClN7O2
  • MW: 477.95
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lorlatinib-d3

Lorlatinib-d3 is the deuterium labeled Lorlatinib. Lorlatinib (PF-06463922) is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor. Lorlatinib has Kis of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALKL1196M

  • CAS Number: 2131126-22-0
  • MF: C21H16D3FN6O2
  • MW: 409.43
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lapatinib-d7 ditosylate

Lapatinib-d7 (GW572016-d7) ditosylate is the deuterium labeled Lapatinib. Lapatinib (GW572016) is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively[1][2].

  • CAS Number: 1009307-24-7
  • MF: C36H34ClFN4O7S2
  • MW: 753.25900
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Apatinib

Apatinib free base (YN968D1 free base) is an orally bioavailable tyrosine kinase inhibitor, which selectively targets VEGFR-2 (IC50=1 nM). Apatinib free base (YN968D1 free base) is an anti-angiogenic drug for the treatment of advanced or metastatic gastric cancer. Apatinib free base (YN968D1 free base) potently inhibits Ret, c-Kit and c-Src with IC50s of 13, 429 and 530 nM, respectively. It also inhibits cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ[1][2][3].

  • CAS Number: 811803-05-1
  • MF: C24H23N5O
  • MW: 397.472
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 578.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 303.5±30.1 °C

Lactacystin

Lactacystin, an antibiotic Streptomyces spp. metabolite, is a potent and selective proteasome inhibitor with an IC50 of 4.8 μM for 20S proteasome. Lactacystin also inhibits the lysosomal enzyme cathepsin A[1]. Lactacystin inhibits cell growth and induces neurite outgrowth[2].

  • CAS Number: 133343-34-7
  • MF: C15H24N2O7S
  • MW: 376.425
  • Catalog: Apoptosis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 714.9±60.0 °C at 760 mmHg
  • Melting Point: 233-235ºC dec.
  • Flash Point: 386.1±32.9 °C

GIP (3-42), human

GIP (3-42), human acts as a glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist, moderating the insulin secreting and metabolic actions of GIP in vivo[1].

  • CAS Number: 1802086-25-4
  • MF: C216H325F3N58O65S
  • MW: 4749.9
  • Catalog: Insulin Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IRAK4-IN-14

IRAK4-IN-14 (compound 28) is a potent, selective and orally active IRAK4 inhibitor with an IC50 of 0.003 µM. IRAK4-IN-14 shows good PK parameters in rats and mouse. IRAK4-IN-14 shows synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with Acalabrutinib[1].

  • CAS Number: 2667681-71-0
  • MF: C25H28FN9O
  • MW: 489.55
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Antiproliferative agent-34

Antiproliferative agent-34 (Compound A14) is a multi-target kinase inhibitor, with an IC50 of 177 nM and 1567 nM for EGFR L858R/T790M and EGFR WT. Antiproliferative agent-34 also inhibits JAK2, ROS1, FLT3, FLT4, PDGFRα with IC50 of 30.93, 106.90, 108.00, 226.60, 42.53 nM. Antiproliferative agent-34 inhibits H1975 and HCC827 cells proliferation with IC50 values below 40 nM under normoxic condition, and the anti-proliferation potency achieves 4–6-fold improvement (IC50 values < 10 nM) under hypoxic condition[1].

  • CAS Number: 2910858-34-1
  • MF: C27H27N7O5
  • MW: 529.55
  • Catalog: EGFR
  • 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

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

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

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

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

Tyrphostin B42 (AG-490)

AG-490 is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.

  • CAS Number: 133550-30-8
  • MF: C17H14N2O3
  • MW: 294.305
  • Catalog: Autophagy
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 615.2±55.0 °C at 760 mmHg
  • Melting Point: 215°C(lit.)
  • Flash Point: 325.9±31.5 °C

H1-7 acetate salt

H1-7 (histone H1 phosphorylation site), PKA Substrate, a synthetic polypeptide, can be used as PKA substrate[1][2].

  • CAS Number: 65189-70-0
  • MF: C31H58N14O9
  • MW: 770.88100
  • Catalog: PKA
  • Density: 1.54g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A