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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LY 456236

LY456236 is a selective, non-competitive and orally active mGlu1 receptor antagonist that inhibits phosphoinositide hydrolysis with an IC50 of 0.145 μM. LY456236 also inhibits EGFR with an IC50 of 0.91 μM[1][3].

  • CAS Number: 338736-46-2
  • MF: C16H16ClN3O2
  • MW: 317.770
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC IRAK4 degrader-8

PROTAC IRAK4 degrader-8 (compound 2) is a PROTAC targeting to IRAK4 (IC50=15.5 nM)[1].

  • CAS Number: 2911615-06-8
  • MF: C43H50ClF2N11O5
  • MW: 874.38
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

tolimidone

Tolimidone is a potent and selective allosteric activator of Lyn kinase with an EC50 of 63 nM.

  • CAS Number: 41964-07-2
  • MF: C11H10N2O2
  • MW: 202.209
  • Catalog: Src
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: 163-164ºC
  • Flash Point: N/A

ALK/EGFR-IN-3

ALK/EGFR-IN-3 is a dual inhibitor of ALK and EGFR. ALK/EGFR-IN-3 inhibits the cell proliferation of H1975, PC9, and Baf3-EML4-ALK cancer cell lines with IC50s of 0.1360, 0.0332, and 0.0339 μM, respectively[1].

  • CAS Number: 2730432-72-9
  • MF: C27H34ClN7O3S
  • MW: 572.12
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CHMFL-EGFR-202

CHMFL-EGFR-202 is a potent, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant kinase, with IC50s of 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases, respectively. CHMFL-EGFR-202 exhibits ∼10-fold selectivity for EGFR L858R/T790M against the EGFR wild-type in cells. CHMFL-EGFR-202 adopts a covalent “DFG-in-C-helix-out” inactive binding conformation with EGFR, with strong antiproliferative effects against EGFR mutant-driven nonsmall-cell lung cancer (NSCLC) cell lines[1].

  • CAS Number: 2089381-40-6
  • MF: C25H24ClN7O2
  • MW: 489.96
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UCN-02

UCN-02 (7-epi-Hydroxystaurosporine) is a selective protein kinase C (PKC) inhibitor produced by Streptomyces strain N-12, with IC50s of 62 nM and 250 nM for PKC and protein kinase A (PKA), respectively. UCN-02 (7-epi-Hydroxystaurosporine) displays cytotoxic effect on the growth of HeLa S3 cells[1][2].

  • CAS Number: 121569-61-7
  • MF: C28H26N4O4
  • MW: 482.537
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Irbinitinib

Tucatinib (Irbinitinib; ARRY-380; ONT-380) is a potent and selective HER2 inhibitor with an IC50 of 8 nM.

  • CAS Number: 937263-43-9
  • MF: C26H24N8O2
  • MW: 480.521
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Harmine

Harmine is a natural dual-specificity tyrosine phosphorylation-regulated kinase ((DYRK)) inhibitor with anticancer and anti-inflammatory activities.

  • CAS Number: 442-51-3
  • MF: C13H12N2O
  • MW: 212.247
  • Catalog: RAD51
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 421.4±40.0 °C at 760 mmHg
  • Melting Point: 262-264 °C(lit.)
  • Flash Point: 139.8±17.0 °C

SU5204

SU5204, a tyrosine kinase inhibitor extracted from patent US5792783A, has IC50s of 4 and 51.5 μM for FLK-1 (VEGFR-2) and HER2, respectively[1].

  • CAS Number: 186611-11-0
  • MF: C17H15NO2
  • MW: 265.30700
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Crizotinib (PF-02341066)

Crizotinib is a potent inhibitor of c-Met and ALK with an IC50 of 11 nM and 24 nM in cell-based assays, respectively.

  • CAS Number: 877399-52-5
  • MF: C21H22Cl2FN5O
  • MW: 450.337
  • Catalog: Autophagy
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 599.2±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 316.2±30.1 °C

F-1

F-1 is a potent ALK and ROS1 dual inhibitor, suppresses phospho-ALK and its relative downstream signaling pathways, with IC50s of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM for ALKWT, ROS1WT, ALKL1196M and ALKG1202R, respectively[1].

  • CAS Number: 2244775-31-1
  • MF: C22H27ClN8O3S
  • MW: 519.02
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CSF1R-IN-8

CSF1R-IN-8 (Compound 22) is a CSF-1R inhibitor with an IC50 of 0.012 μM[1].

  • CAS Number: 2765301-60-6
  • MF: C24H22N4O4
  • MW: 430.46
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK143 dihydrochloride

GSK143 dihydrochloride is an orally active and highly selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.5. GSK143 dihydrochloride inhibits phosphorylated Erk (pErk: pIC50=7.1)[1]. GSK143 dihydrochloride reduces inflammation and prevents recruitment of immune cells in the intestinal muscularis in mice[2][3].

  • CAS Number: 2341796-81-2
  • MF: C17H24Cl2N6O2
  • MW: 415.32
  • Catalog: PERK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pentagamavunon-1

Pentagamavunon-1 (PGV-1), a Curcumin analog with oral activity, targets on several molecular mechanisms to induce apoptosis including inhibition of angiogenic factors cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). PGV-1 inhibits NF-κB activation[1].

  • CAS Number: 27060-70-4
  • MF: C23H24O3
  • MW: 348.43
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lapatinib-d5

Lapatinib-d5 is 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].

  • CAS Number: 2748212-14-6
  • MF: C29H21D5ClFN4O4S
  • MW: 586.09
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNF-2

GNF-2 is a highly selective non-ATP competitive inhibitor of oncogenic Bcr-Abl activity (IC50 = 0.14 μM).IC50 value: 0.14 uM [1]Target: Bcr-Ablin vitro: Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs [2]. GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner [3].GNF-2 dose-dependently inhibited the proliferation of osteoclast precursors through the suppression of the M-CSFR c-Fms. In addition, GNF-2 accelerated osteoclast apoptosis by inducing caspase-3 and Bim expression. Furthermore, GNF-2 interfered with actin cytoskeletal organization and subsequently blocked the bone-resorbing activity of mature osteoclasts [4].in vivo: Combining PDMP and GNF-2 eliminated transplanted-CML-T315I-mutants in vivo and dose dependently sensitized primary cells from CML T315I patients to GNF-2-induced proliferation inhibition and apoptosis[5].

  • CAS Number: 778270-11-4
  • MF: C18H13F3N4O2
  • MW: 374.317
  • Catalog: Bcr-Abl
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 536.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 278.2±30.1 °C

TAE684(NVP-TAE684)

NVP-TAE 684 is a highly potent and selective ALK inhibitor, which blocks the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM.

  • CAS Number: 761439-42-3
  • MF: C30H40ClN7O3S
  • MW: 614.202
  • Catalog: ALK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 791.0±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 432.2±35.7 °C

Sotuletinib hydrochloride

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

  • CAS Number: 2222138-31-8
  • MF: C20H23ClN4O3S
  • MW: 434.94
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SNIPER(ABL)-058

SNIPER(ABL)-058, conjugating Imatinib (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 10 μM[1].

  • CAS Number: 2222354-61-0
  • MF: C62H75N11O9S
  • MW: 1150.39
  • Catalog: Bcr-Abl
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC-S 7004

Mirk-IN-1 is a potent inhibitor of Dyrk1B(Mirk kianse) and Dyrk1A with IC50 of 68±48 nM and 22±8 nM respectively.IC50 value: 68±48/22±8 nM (Dyrk1B/Dyrk1A) [1]Target: Dyrk inhibitorMirk-IN-1 had an EC50 of 1.9 ±0.2 mmol/L on SW620 cells. At a much higher concentration of 10 mmol/L in a kinase assay, Mirk-IN-1 inhibited the activities of DYRK1A, ABL, FLT3, and MARK1 by88%, 64%, 56%, and 73%, respectively [1]. Mirk-IN-1 was able to block tumor cells from undergoing reversible arrest in a quiescent G0 state and enable some cells to exit quiescence [2].

  • CAS Number: 1386979-55-0
  • MF: C23H17Cl2N5O4
  • MW: 498.318
  • Catalog: DYRK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hydroxytanshinone IIA

Hydroxytanshinone IIA is a hydroxylated metabolite of Tanshinone IIA. Tanshinone IIA may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2[1].

  • CAS Number: 18887-18-8
  • MF: C19H18O4
  • MW: 310.344
  • Catalog: VEGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 523.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 270.4±30.1 °C

Gefitinib dihydrochloride

Gefitinib (ZD 1839) dihydrochloride is a potent, selective and orally active EGFR tyrosine kinase inhibitor with an IC50 of 33 nM. Gefitinib dihydrochloride selectively inhibits EGF-stimulated tumor cell growth (IC50 of 54 nM) and blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Gefitinib dihydrochloride also induces autophagy and cell apoptosis, which can be used for cancer related research, such as Lung cancer and breast cancer [1][2][5].

  • CAS Number: 184475-56-7
  • MF: C22H26Cl3FN4O3
  • MW: 519.824
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 628.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 333.7ºC

2-Phenyl-6,7-dimethylquinoxaline

AG 1295 is a selective platelet-derived growth factor receptor (PDGFR) tyrosine-kinase inhibitor. AG 1295 reduces neointimal formation in aortic allograft vasculopathy by inhibition of PDGFR-beta-triggered tyrosine phosphorylation[1][2].

  • CAS Number: 71897-07-9
  • MF: C16H14N2
  • MW: 234.296
  • Catalog: PDGFR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 398.3±37.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.4±17.8 °C

ErbB-2-binding peptide

ErbB-2-binding peptide (HER2-binding peptide) is a tumor-binding peptide. ErbB-2-binding peptide has the potential for cancer research[1].

  • CAS Number: 562791-56-4
  • MF: C43H60N8O11
  • MW: 864.98
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SU5416

Semaxinib (SU5416) is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) with an IC50 of 1.23 μM.

  • CAS Number: 204005-46-9
  • MF: C15H14N2O
  • MW: 238.285
  • Catalog: VEGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 481.4±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 244.9±28.7 °C

Lucitanib

Lucitanib (E-3810) is a novel dual inhibitor of VEGFR and FGFR, potently and selectively inhibits VEGFR1, VEGFR2, VEGFR3, FGFR1 and FGFR2 with IC50s of 7 nM, 25 nM, 10 nM, 17.5 nM, and 82.5 nM, respectively.

  • CAS Number: 1058137-23-7
  • MF: C26H25N3O4
  • MW: 443.49400
  • Catalog: FGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zidesamtinib

Zidesamtinib (NVL-520) is a potent, selective, orally active and brain-penetrant inhibitor of diverse ROS1 fusions and resistance mutations, with IC50s of 0.7 and 7.9 nM for wild-type ROS1 and ROS1 G2032R, respectively, and spares TRK inhibition. Zidesamtinib can be used for the research of cancer[1].

  • CAS Number: 2739829-00-4
  • MF: C22H22FN7O
  • MW: 419.45
  • Catalog: ROS
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HA-100

HA-100 is an inhibitor of cGMP-dependent protein kinase (PKG), cAMP-dependent protein kinase (PKA), Protein kinase C (PKC) and MLC-kinase with IC50s of 4, 8, 12 and 240 μM, respectively.

  • CAS Number: 84468-24-6
  • MF: C13H15N3O2S
  • MW: 277.34200
  • Catalog: Myosin
  • Density: 1.332g/cm3
  • Boiling Point: 497.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 254.6ºC

c-ABL-IN-2

c-ABL-IN-2 is a potent inhibitor of c-Abl. Activation of c-Abl has been implicated in various diseases, notably cancer. c-ABL-IN-2 has the potential for the research of neurodegenerative diseases (amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) and cancer (extracted from patent WO2020260871A1, compound 25)[1].

  • CAS Number: 2574593-54-5
  • MF: C21H20N4O
  • MW: 344.41
  • Catalog: Bcr-Abl
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Efruxifermin

Efruxifermin is an Fc-FGF21 fusion protein (human IgG1 Fc domain linked to a modified human FGF21). Efruxifermin has prolonged half-life and enhanced receptor affinity compared with native human FGF21. Efruxifermin can be used for the research of non-alcoholic steatohepatitis[1].

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