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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PLB-1001

Bozitinib (PLB-1001) is a highly selective c-MET kinase inhibitor with blood-brain barrier permeability. Bozitinib (PLB-1001) is a ATP-competitive small-molecule inhibitor, binds to the conventional ATP-binding pocket of the tyrosine kinase superfamily[1].

  • CAS Number: 1440964-89-5
  • MF: C20H15F3N8
  • MW: 424.38
  • Catalog: c-Met/HGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PKI (14-24)amide TFA

PKI (14-24)amide TFA is a potent PKA inhibitor. PKI (14-24)amide strongly inhibited cyclic AMP-dependent protein kinase activity in the cell homogenate[1][2].

  • CAS Number: 1293946-39-0
  • MF: C51H87F3N24O17
  • MW: 1365.38
  • Catalog: PKA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Chmfl-btk-01

CHMFL-BTK-01 (compound 9) is a highly selective irreversible BTK inhibitor, with an IC50 of 7 nM. CHMFL-BTK-01 (compound 9) potently inhibited BTK Y223 auto-phosphorylation[1].

  • CAS Number: 2095280-64-9
  • MF: C38H41N5O5
  • MW: 647.76
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dusigitumab

Dusigitumab (MEDI 573) is a human IgG2λ monoclonal antibody that specifically targets IGF2 and IGF1[1].

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

PROTAC IRAK4 degrader-1

PROTAC IRAK4 degrader-1 is a PROTAC interleukin-1 receptor-associated kinase 4 (IRAK4) degrader extracted from patent US20190192668A1 Compound I-210, makes <20%, >20-50%, and >50% IRAK4 degradation at 0.01, 0.1, and 1 μM in OCI-LY-10 cells, respectively[1].

  • CAS Number: 2360533-90-8
  • MF: C44H39F3N12O7
  • MW: 904.85
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fenlean

Fenlean, a natural squamosamide derivative, is a Src tyrosine kinase inhibitor. Fenlean can inhibit over-activated microglia and protect dopaminergic neurons. Fenlean can attenuate neuroinflammation in Parkinson's disease models[1][2][3].

  • CAS Number: 863193-70-8
  • MF: C26H27NO6
  • MW: 449.50
  • Catalog: Src
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Insulin efsitora alfa

Insulin efsitora alfa (LY-3209590) is a selective agonist of insulin receptor (IR). Insulin efsitora alfa is a fusion protein composed of human IR agonists fused with the crystallizable (Fc) domain of human immunoglobulin G2 (IgG2) fragment, with a molecular weight of 64.1 kDa. Insulin efsitora alfa is well tolerated and has potential applications in diabetes patients[1].

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

DZD1516

DZD1516 is a potent and selective HER2 inhibitor (IC50=0.56 nM) with good blood-brain permeability. DZD1516 exhibits antitumor activity in CNS and subcutaneous xenograft mouse models[1].

  • CAS Number: 2387570-00-3
  • MF: C28H27F2N7O3
  • MW: 547.56
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Takeda-6d

Takeda-6D (compound 6d) is an orally active and potent BRAF/VEGFR2 inhibitor, with IC50 values of 7.0 and 2.2 nM, respectively. Takeda-6D shows antiangiogenesis by suppressing the VEGFR2 pathway in 293/KDR and VEGF-stimulated HUVEC cells.Takeda-6D shows significant suppression of ERK1/2 phosphorylation. Takeda-6D shows antitumor activity[1].

  • CAS Number: 1125632-93-0
  • MF: C27H19ClFN5O3S
  • MW: 547.988
  • Catalog: PERK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Parsatuzumab

Parsatuzumab (Anti-EGFL7; RG 7414) is a humanized monoclonal antibody, acts as an immunomodulator and binds to EGFL7. Parsatuzumab selectively blocks the interaction between EGFL7 and endothelial cells, potentially inhibiting vascular regrowth and reducing vascular endothelial growth factor (VEGF) inhibition[1].

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

Syk-IN-3

Syk-IN-3, a potent spleen tyrosine kinase (Syk) inhibitor, extracted from patent WO2011075515A1, compound example 152, has an IC50 of 1 nM[1].

  • CAS Number: 1312534-69-2
  • MF: C24H28N4O3S
  • MW: 452.57
  • Catalog: Syk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Masitinib (mesylate)

Masitinib mesylate is a novel inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, and has weak inhibition to ABL and c-Fms.

  • CAS Number: 1048007-93-7
  • MF: C29H34N6O4S2
  • MW: 594.74800
  • Catalog: c-Kit
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BCR-ABL-IN-8

BCR-ABL-IN-8 (compound 26f) is a BCR-ABL inhibitor containing trimethoxy group[1].

  • CAS Number: 1808288-49-4
  • MF: C30H33N7O5
  • MW: 571.63
  • Catalog: Bcr-Abl
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PDE5-IN-3

PDE5-IN-3 (compound 11j) is a potent PDE5 inhibitor with an IC50 of 1.57 nM. PDE5-IN-3 shows moderate EGFR inhibition with IC50 of 5.827 µM. PDE5-IN-3 significantly inhibits the Wnt/β-catenin pathway (IC50=1286.96 ng/mL). PDE5-IN-3 induces the intrinsic apoptotic mitochondrial pathway in HepG2 cells. PDE5-IN-3 has strong antitumor activity[1].

  • CAS Number: 2538149-57-2
  • MF: C21H14BrN5O2
  • MW: 448.27
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Labuxtinib

Labuxtinib is c-kit tyrosine kinase inhibitor[1].

  • CAS Number: 1426449-01-5
  • MF: C20H16FN5O2
  • MW: 377.37
  • Catalog: c-Kit
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

VEGFR-2-IN-6

VEGFR-2-IN-6 (example 64) is a VEGFR2 inhibitor (angiogenesis modulator), which is extracted from patent WO 02/059110[1].

  • CAS Number: 444731-47-9
  • MF: C20H21N7O2S
  • MW: 423.49
  • Catalog: VEGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(E)-FeCP-oxindole

(Z)-FeCP-oxindole is a selective human vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with an IC50 value of 200 nM. (Z)-FeCP-oxindole can significantly inhibit VEGFR1 and PDGFRa or b at 10 μM. (Z)-FeCP-oxindole has some anticancer activity, acting on B16 murine melanoma lines with IC50 less than 1 μM[1].

  • CAS Number: 884338-18-5
  • MF: C19H15FeNO
  • MW: 329.17
  • Catalog: VEGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TAK-659 hydrochloride

TAK-659 hydrochloride is a potent, selective and orally available spleen tyrosine kinase (Syk) inhibitor with an IC50 of 3.2 nM.

  • CAS Number: 1952251-28-3
  • MF: C17H22ClFN6O
  • MW: 380.85
  • Catalog: Syk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrphostin AG 1296

Tyrphostin AG1296 is a potent and selective inhibitor of platelet-derived growth factor receptor (PDGFR), with an IC50 of 0.8 μM. Tyrphostin AG1296 inhibits signaling of human PDGF α- and β-receptors as well as of the related stem cell factor receptor (c-Kit). Tyrphostin AG1296 is also a potent inhibitor of FLT3, with an IC50 in the micromolar range[1][2][3].

  • CAS Number: 146535-11-7
  • MF: C16H14N2O2
  • MW: 266.295
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 420.2±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 151.8±17.6 °C

Tyrphostin AG 1433

Tyrphostin AG 1433 is a specific and potent inhibitor of PDGFR-β and of KDR/Flk-1. Tyrphostin AG 1433 acts as an angiogenesis inhibitor[1].

  • CAS Number: 168836-03-1
  • MF: C16H14N2O2
  • MW: 266.29500
  • Catalog: PDGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GDC-0834 (RaceMate)

GDC-0834 Racemate is the racemate form of GDC-0834, which is a potent and selective BTK inhibitor with in vitro IC50s of 5.9 and 6.4 nM in biochemical and cellular assays, respectively.IC50 value: 5.9 nM/6.4 nM(biochemical/cellular assay) [1]Target: BTKin vitro: GDC-0834 inhibited BTK with an in vitro IC(50) of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and in vivo IC(50) of 1.1 and 5.6 μM in mouse and rat, respectively [1].in vivo: Administration of GDC-0834 (30-100 mg/kg) in a rat collagen-induced arthritis (CIA) model resulted in a dose-dependent decrease of ankle swelling and reduction of morphologic pathology [1]. GDC-0834 exhibited low clearance in PXB chimeric mice with humanized liver. Uncertainty in human pharmacokinetic prediction and high interest in a BTK inhibitor for clinical evaluation prompted an investigational new drug strategy, in which GDC-0834 was rapidly advanced to a single-dose human clinical trial. GDC-0834 plasma concentrations in humans were below the limit of quantitation (<1 ng/ml) in most samples from the cohorts dosed orally at 35 and 105 mg [2].

  • CAS Number: 1133432-46-8
  • MF: C33H36N6O3S
  • MW: 596.742
  • Catalog: Btk
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EML4-ALK kinase inhibitor 1

EML4-ALK kinase inhibitor 1 is a potent oral active inhibitor of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), with an IC50 of 1 nM[1].

  • CAS Number: 1373409-08-5
  • MF: C31H48N8O3
  • MW: 580.76
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TX1-85-1

TX1-85-1 is a Her3 (ErbB3) inhibitor with an IC50 of 23 nM. TX1-85-1 induces partial degradation of Her3 protein and attenuates Her3-dependent signaling[1].

  • CAS Number: 1603845-32-4
  • MF: C32H36N8O3
  • MW: 580.679999999999
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AG-825

AG-825 (Tyrphostin AG-825) is a selective and ATP-competitive ErbB2 inhibitor which suppresses tyrosine phosphorylation, with an IC50 of 0.35 μM. AG-825 displays anti-cancer activity[1][2][3]. AG825 significantly accelerates apoptosis of human neutrophils[4]. AG-825 is a potential agent for overcoming Mn-induced neurotoxicity or AD development[5].

  • CAS Number: 149092-50-2
  • MF: C19H15N3O3S2
  • MW: 397.471
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 689.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 370.7±34.3 °C

Duligotuzumab

Duligotuzumab (MEHD-7945A; RG 7597) is a humanized IgG-κ monoclonal antibody that specifically targets Her3 (ErbB3)[1].

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

DPPY

DPPY (compound 6) is a potent PTK inhibitor with IC50 values of <10, <10, <10 nM for EGFR, BTK, JAK3, respectively. DPPY shows anti-proliferative activity against B-cell lymphoma cells. DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].

  • CAS Number: 2095883-62-6
  • MF: C25H26ClN7O3
  • MW: 507.97
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HG-12-6

HG-12-6 is a small-molecule inhibitor that bind preferentially to unphosphorylated IRAK4 with IC50 of 165.1 nM, displays 15-fold selectivity over phosphorylated IRAK4 (IC50=2876 nM); binds as type II inhibitor with IRAK4 in a “DFG-out” conformation.

  • CAS Number: 2222354-57-4
  • MF: C29H27F3N6O2S
  • MW: 580.63
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTK-IN-20

BTK-IN-20 (compound 283) is a BTK tyrosine kinase inhibitor and a 1H-pyrazolo[3,4-d]pyrimidine derivative. BTK-IN-20 can be used for the research of cancer and inflammation[1].

  • CAS Number: 1581714-50-2
  • MF: C30H30FN7O2
  • MW: 539.60
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sunvozertinib

Sunvozertinib is a potent ErbBs (EGFR, Her2, especially mutant forms) and BTK inhibitor. Sunvozertinib shows IC50s of 20.4, 20.4, 1.1, 7.5, and 80.4 nM for EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R and T790M mutations, and Her2 Exon20 YVMA, and EGFR WT A431, respectively (patent WO2019149164A1, example 52)[1].

  • CAS Number: 2370013-12-8
  • MF: C29H35ClFN7O3
  • MW: 584.08
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vanucizumab

Vanucizumab is a first-in-class, bispecific IgG1-like monoclonal antibody that simultaneously blocks VEGF-A and angiopoietin-2 (Ang-2) from interacting with their receptors. Vanucizumab has antiangiogenic and anticancer effects[1].

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