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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DCC-3014

DCC-3014 is a c-FMS (CSF-IR) and c-Kit dual inhibitor extracted from patent WO2014145025A2, Compound Example 10, has IC50s of <0.01 μM and 0.1-1 μM, respectively[1].

  • CAS Number: 1628606-05-2
  • MF: C23H25N7O2
  • MW: 431.49
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

USP10 inhibitor Wu-5

USP10 inhibitor Wu-5 (Wu-5) is a novel small molecule USP10 inhibitor inducing the degradation of FLT3-mutated protein, directly interacts and inactivates USP10, the deubiquitinase for FLT3-ITD in vitro (IC50=8.3 uM) and in FLT3-ITD-positive AML cells.Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC50 of 3.794, 5.056, and 8.386 uM, respectively.Wu-5 (1-10 μM) dose-dependently induced apoptosis of MV4-11, Molm13, and MV4-11R cells through the proteasome-mediated degradation of FLT3-ITD.Combined treatment of Wu-5 and crenolanib produced synergistic cell death in FLT3-ITD-positive cells via the reduction of both FLT3 and AMPKα proteins.

  • CAS Number: 2630378-05-9
  • MF: C15H13NO7S
  • MW: 351.329
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FGFR1/DDR2 inhibitor 1

FGFR1/DDR2 inhibitor 1 (compound 11k) is an inhibitor of fibroblast growth factor receptor 1 (FGFR1) and discoindin domain receptor 2 (DDR2), with IC50 values of 31.1 nM, 108.4 nM and 3.2 nM for FGFR1, KG-1, and DDR2, respectively[1].

  • CAS Number: 2308497-58-5
  • MF: C28H22F3N5O
  • MW: 501.50
  • Catalog: FGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/CDK2-IN-1

EGFR/CDK2-IN-1 (Compound 3b) is an EGFR/CDK2 inhibitor. EGFR/CDK2-IN-1 shows good cytotoxicity against MCF7 and HepG2 cells. EGFR/CDK2-IN-1 can be used in cancer research[1].

  • CAS Number: 2841405-96-5
  • MF: C19H12BrClO2
  • MW: 387.65
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neratinib-d6

Neratinib-d6 (HKI-272-d6) is the deuterium labeled Neratinib. Neratinib (HKI-272) is an orally available, irreversible tyrosine kinase inhibitor with IC50s of 59 nM and 92 nM for HER2 and EGFR, respectively.

  • CAS Number: 1259519-18-0
  • MF: C30H23D6ClN6O3
  • MW: 563.08
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ganitumab

Ganitumab (AMG 479) is a recombinant human monoclonal antibody to the human type 1 insulin-like growth factor receptor (IGF1R). Ganitumab recognizes murine IGF1R with sub-nanomolar affinity (KD=0.22 nM) and inhibits the interaction of murine IGF1R with IGF1 and IGF2. Ganitumab can be used in research of cancer[1].

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

Degrasyn(WP1130)

Degrasyn (WP1130) is a cell-permeable deubiquitinase (DUB) inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37. Degrasyn has been shown to downregulate the antiapoptotic proteins Bcr-Abl and JAK2.

  • CAS Number: 856243-80-6
  • MF: C19H18BrN3O
  • MW: 384.270
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 582.1±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 305.9±30.1 °C

TRK-IN-14

TRK-IN-14 is a potent inhibitor of TRK. Protein kinases play a critical role in the control of cell growth and differentiation and are responsible for the control of a wide variety of cellular signal transduction processes. TRK-IN-14 has the potential for the research of TRK-related diseases (extracted from patent WO2012034091A1, compound X-47)[1].

  • CAS Number: 1365212-84-5
  • MF: C24H21F2N5O
  • MW: 433.45
  • Catalog: Trk Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Robatumumab

Robatumumab (Sch 717454) is an anti-human IGF-1R (insulin-like growth factor receptor-1) antibody. Robatumumab shows anti-tumor activity and anti-proliferative activity to cancer cells. Robatumumab can be used in osteosarcoma and Ewing sarcoma research[1][2].

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

Nilotinib-d3

Nilotinib-d3 (AMN107-d3) is the deuterium labeled Nilotinib. Nilotinib is an orally available Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity[1][2].

  • CAS Number: 1215678-43-5
  • MF: C28H19D3F3N7O
  • MW: 532.53400
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AT7867

AT7867 is a potent ATP-competitive inhibitor of Akt1/Akt2/Akt3 and p70S6K/PKA with IC50s of 32 nM/17 nM/47 nM and 85 nM/20 nM, respectively.

  • CAS Number: 857531-00-1
  • MF: C20H20ClN3
  • MW: 337.846
  • Catalog: Ribosomal S6 Kinase (RSK)
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 530.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 274.5±30.1 °C

Trafermin

Trafermin is a recombinant human basic fibroblast growth factor (rhbFGF). Trafermin is a potent FGFR inhibitor. Trafermin improves degree of re-epithelialization. Trafermin can be used in research in skin healing[1].

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

FAK-IN-14

FAK-IN-14 (compound 8d) is a focal adhesion kinase(FAK) inhibitor with an IC50 value of 0.2438 nM. FAK-IN-14 induces U87-MG cell early apoptosis and arrest the cell at the G2/M phase[1].

  • CAS Number: 2766666-22-0
  • MF: C21H24BrN7OS
  • MW: 502.43
  • Catalog: FAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IRAK inhibitor 2

IRAK inhibitor 2 is interleukin-1 receptor associated kinase inhibitor .

  • CAS Number: 928333-30-6
  • MF: C17H14N4O2
  • MW: 306.31900
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrosine kinase-IN-6

Tyrosine kinase-IN-6 is a potent and promising RON splice variants inhibitor with anti-cancer and o?antineoplastic effects[1].

  • CAS Number: 2377507-01-0
  • MF: C37H31F2N5O5S
  • MW: 695.73
  • Catalog: c-Met/HGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nelipepimut-S

Nelipepimut-S is a peptide vaccine which targets HER2. Nelipepimut-S has immune activity against HER2 positive breast cancer[1].

  • CAS Number: 160212-35-1
  • MF: C50H78N10O11
  • MW: 995.215
  • Catalog: EGFR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 1354.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 773.0±34.3 °C

TG 100572 (Hydrochloride)

TG 100572 Hydrochloride is a multi-targeted kinase inhibitor which inhibits receptor tyrosine kinases and Src kinases; has IC50s of 2, 7, 2, 16, 13, 5, 0.5, 6, 0.1, 0.4, 1, 0.2 nM for VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRβ, Fgr, Fyn, Hck, Lck, Lyn, Src, Yes, respectively.

  • CAS Number: 867331-64-4
  • MF: C26H27Cl2N5O2
  • MW: 512.43100
  • Catalog: Src
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

YF-452

YF-452 is a potential antiangiogenic drug candidate for cancer therapy.

  • CAS Number: 1951466-83-3
  • MF: C24H26BrN3O
  • MW: 452.39
  • Catalog: VEGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pelitinib

Pelitinib (EKB-569;WAY-EKB 569) is an irreversible inhibitor of EGFR with an IC50 of 38.5 nM; also slightly inhibits Src, MEK/ERK and ErbB2 with IC50s of 282, 800, and 1255 nM, respectively.

  • CAS Number: 257933-82-7
  • MF: C24H23ClFN5O2
  • MW: 467.923
  • Catalog: Src
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 655.5±55.0 °C at 760 mmHg
  • Melting Point: 173-178ºC
  • Flash Point: 350.2±31.5 °C

Timigutuzumab

Timigutuzumab (GEXMab73) is a humanized monoclonal antibody that targets ErbB2. Timigutuzumab can be used for the research of cancer[1].

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

EGFR/HER2/TS-IN-2

EGFR/HER2/TS-IN-2 (compound 17) is a potent EGFR/HER2 and TS (Thymidylate synthase) inhibitor, with IC50 values of 0.173, 0.125, and 1.12 μM, respectively. EGFR/HER2/TS-IN-2 shows cytotoxic activity against MDA-MB-231 cancer cell lines, with an IC50 of 1.69 µM[1].

  • CAS Number: 2444364-04-7
  • MF: C26H21N7OS2
  • MW: 511.62
  • Catalog: Thymidylate Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HP1328

HP1328 is a potent inhibitor of FLT3 receptor tyrosine kinase (FLT3/ITD mutation). HP1328 is a benzoimidazole scaffold-based compound. HP1328 significantly reduces the leukemia burden and prolongs the survival of mice with FLT3/ITD leukemia[1].

  • CAS Number: 2245074-20-6
  • MF: C23H23N3O3
  • MW: 389.45
  • Catalog: FLT3
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNJ-47117096 hydrochloride

JNJ-47117096 hydrochloride is potent and selective MELK inhibitor, with an IC50 of 23 nM, also effectively inhibits Flt3, with an IC50 of 18 nM.

  • CAS Number: 1610536-69-0
  • MF: C21H23ClN4O2
  • MW: 398.886
  • Catalog: MELK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fasudil Hydrochloride Hydrate

Fasudil (HA-1077; AT877) hydrochloride semihydrate is a nonspecific RhoA/ROCK inhibitor and also has inhibitory effect on protein kinases, with an Ki of 0.33 μM for ROCK1, IC50s of 0.158 μM and 4.58 μM, 12.30 μM, 1.650 μM for ROCK2 and PKA, PKC, PKG, respectively. Fasudil hydrochloride semihydrate is also a potent Ca2+ channel antagonist and vasodilator[1][2][3].

  • CAS Number: 186694-02-0
  • MF: C28H38Cl2N6O5S2
  • MW: 673.67500
  • Catalog: HIV
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lenvatinib Mesylate

Lenvatinib mesylate (E7080 mesylate), an oral, multi-targeted tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFR, KIT, and RET, shows potent antitumor activities[1][2].

  • CAS Number: 857890-39-2
  • MF: C22H23ClN4O7S
  • MW: 522.959
  • Catalog: c-Kit
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sp-cAMPS

Sp-cAMPS, a cAMP analog, is potent activator of cAMP-dependent PKA I 和 PKA II. Sp-cAMPS is also a potent, competitive phosphodiesterase (PDE3A) inhibitor with a Ki of 47.6 µM. Sp-cAMPS binds the PDE10 GAF domain with an EC50 of 40 μM[1][2][3].

  • CAS Number: 71774-13-5
  • MF: C10H12N5O5PS
  • MW: 345.27200
  • Catalog: Phosphodiesterase (PDE)
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A