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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Ficlatuzumab

Ficlatuzumab is a monoclonal antibody (McAb) targeting human hepatocyte growth factor (HGF). Ficlatuzumab blocks the activation of the HGF/c-Met signaling pathway, and inhibits c-Met receptor-mediated cancer cell proliferation, migration, and invasion[1].

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

1-Naphthyl PP1 (hydrochloride)

1-Naphthyl PP1(1-NA-PP1) hydrochloride is a selective inhibitor of src family kinases v-Src and c-Fyn as well as the tyrosine kinase c-Abl (IC50 values are 1.0, 0.6, 0.6, 18 and 22 μM for v-Src, c-Fyn, c-Abl, CDK2 and CAMK II respectively).IC50 Value:1.0 uM (v-Src); 0.6 uM (c-Fyn); 18 uM (c-Abl) [1]Target: Src Family kinase1-NA-PP1 was considerably more potent and showed distinct substituent effects at the pyrazolopyrimidine core. 1-NA-PP1 was cell-active, and potently blocked prostate cancer cell proliferation by inducing G2/M arrest. Overexpression of PKD1 or PKD3 almost completely reversed the growth arrest and the inhibition of tumor cell invasion caused by 1-NA-PP1, indicating that its anti-proliferative and anti-invasive activities were mediated through the inhibition of PKD. Interestingly, a 12-fold increase in sensitivity to 1-NA-PP1 could be achieved by engineering a gatekeeper mutation in the active site of PKD1, suggesting that 1-NA-PP1 could be paired with the analog-sensitive PKD1(M659G) for dissecting PKD-specific functions and signaling pathways in various biological systems [2].

  • CAS Number: 956025-47-1
  • MF: C19H20ClN5
  • MW: 353.84900
  • Catalog: Src
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mobocertinib mesylate

Mobocertinib (TAK-788) mesylate is an orally active and irreversible EGFR/HER2 inhibitor. Mobocertinib mesylate potently inhibits oncogenic variants containing activating EGFRex20ins mutations with selectivity over wild-type EGFR. Mobocertinib mesylate can be used in NSCLC research[1][2].

  • CAS Number: 2389149-85-1
  • MF: C33H43N7O7S
  • MW: 681.80
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC-IN-63

HDAC-IN-63 (Compound 63) is a dual FLT3/HDAC inhibitor (IC50: 0.844 and 30.0 nM for FLT3 and HDAC1 respectively). HDAC-IN-63 inhibits MV4-11 cell proliferation (IC50: 92 nM. HDAC-IN-63 induces apoptosis and arrests cell cycle in MV4-11 cells. HDAC-IN-63 can be used for research of acute myeloid leukemia (AML)[1].

  • CAS Number: 2920046-95-1
  • MF: C25H26Cl2N6O3
  • MW: 529.42
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isolinderalactone

Isolinderalactone suppresses human glioblastoma growth and angiogenic activity through the inhibition of VEGFR2 activation in endothelial cells[1]. Isolinderalactone suppresses the expression of B-cell lymphoma 2 (Bcl-2), survi

  • CAS Number: 957-66-4
  • MF: C15H16O3
  • MW: 244.29
  • Catalog: Bcl-2 Family
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Defactinib hydrochloride

Defactinib hydrochloride is a novel FAK inhibitor, which inhibits FAK phosphorylation at the Tyr397 site in a time- and dose-dependent manner.

  • CAS Number: 1073160-26-5
  • MF: C20H22ClF3N8O3S
  • MW: 546.95400
  • Catalog: FAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTK-IN-23

BTK-IN-23 is a BTK inhibitor (IC50: 12.8 nM). BTK-IN-23 also inhibits BLX and BMX with IC50s of 35.6 and 5.7 nM respectively. BTK-IN-23 shows improved kinase selectivity compared to Ibrutinib (HY-10997)[1].

  • CAS Number: 2573048-11-8
  • MF: C27H28N6O2
  • MW: 468.55
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ZINC40099027

Novel FAK activator, promoting human intestinal epithelial monolayer wound closure and mouse ulcer healing

  • CAS Number: 1211825-25-0
  • MF: C23H25F3N3O3
  • MW: 449.47
  • Catalog: FAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

X-396 hydrochloride

Ensartinib hydrochloride (X-396 hydrochloride) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively.

  • CAS Number: 2137030-98-7
  • MF: C26H29Cl4FN6O3
  • MW: 634.36
  • Catalog: ALK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NT219

NT219 is a potent and dual inhibitor of insulin receptor substrates 1/2 (IRS1/2) and STAT3. IRS1/2 and STAT3 are major signaling junctions regulated by various oncogenes. NT219 affects IRS1/2 degradation and inhibits STAT3 phosphorylation. NT219 has the potential for the research of cancer diseases[1].

  • CAS Number: 1198078-60-2
  • MF: C16H14BrNO5S
  • MW: 412.26
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Erlotinib-13C6 hydrochloride

Erlotinib-13C6 (hydrochloride) is the 13C labeled Erlotinib Hydrochloride[1]. Erlotinib Hydrochloride (CP-358774 Hydrochloride) inhibits purified EGFR kinase with an IC50 of 2 nM[2].

  • CAS Number: 1210610-07-3
  • MF: C22H24ClN3O4
  • MW: 435.85300
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pp1

PP1 is a potent, and Src family-selective tyrosine kinase inhibitor with IC50 of 5 and 6 nM for Lck and Fyn, respectively.

  • CAS Number: 172889-26-8
  • MF: C16H19N5
  • MW: 281.356
  • Catalog: Src
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 478.8±40.0 °C at 760 mmHg
  • Melting Point: 205-207ºC
  • Flash Point: 243.4±27.3 °C

DPP-4 inhibitor 3

DPP-4 inhibitor 3 (Compound 5a) is a potent dipeptidyl peptidase IV (DPP-IV) inhibitor with an IC50 of 0.75 nM. DPP-4 inhibitor 3 shows excellent antioxidant and insulinotropic activity[1].

  • CAS Number: 2402735-14-0
  • MF: C19H22N6O2
  • MW: 366.42
  • Catalog: Dipeptidyl Peptidase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RIPK2-IN-1

RIPK2-IN-1 (compound 18f) is a potent RIPK2 inhibitor with an IC50 of 51 nM. RIPK2-IN-1 inhibits ALK2 with an IC50 of 5 nM. RIPK2-IN-1 has an IC50 of 390 nM on RIPK2/NOD2 in cell assay[1].

  • CAS Number: 2245820-70-4
  • MF: C23H27N5O3S
  • MW: 453.56
  • Catalog: RIP kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SGX-523

SGX-523 is a selective Met inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α.IC50 value: 4 nM [1]Target: Metin vitro: SGX-523 belongs to the class of c-Met/hepatocyte growth factor receptor (HGFR) tyrosine kinase inhibitors. SGX-523 stabilizes MET in a unique inactive conformation that is inaccessible to other protein kinases, suggesting an explanation for its selectivity. SGX523 potently inhibits the purified MET catalytic domain but not the closely related receptor tyrosine kinase RON. SGX523 indicates ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), with a Ki of 2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), with a Ki of 23 nM], a phenomenon consistent with preferential binding to an inactive enzyme conformation. SGX523 inhibits MET-mediated signaling, cell proliferation and cell migration at nanomolar concentrations but had no effect on signaling dependent on other protein kinases, including the closely related RON, even at micromolar concentrations [1].in vivo: SGX523 significantly retards the growth of preestablished GTL16 tumors when administered orally at doses of ≥10 mg/kg twice daily. SGX523 potently inhibits U87MG tumor growth; at 30 mg/kg dosed twice daily, SGX523 leads to clear regression of U87MG tumors. SGX523, dosed twice daily at 30 mg/kg, also retards the growth of H441 tumors with concomitant reduction in tumor MET autophosphorylation levels. SGX523 inhibition of MET in vivo is associated with the dose-dependent inhibition of growth of tumor xenografts derived from human glioblastoma, lung and gastric cancers, confirming the dependence of these tumors on MET catalytic activity [1].

  • CAS Number: 1022150-57-7
  • MF: C18H13N7S
  • MW: 359.408
  • Catalog: c-Met/HGFR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ALK kinase inhibitor-1

ALK kinase inhibitor-1 is an anaplastic lymphoma kinase (ALK) inhibitor extracted from patent US20130261106A1 compound I-202[1].

  • CAS Number: 1462949-64-9
  • MF: C28H32FN5O3S
  • MW: 537.649
  • Catalog: ALK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 735.9±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 398.8±35.7 °C

AMG-Tie2-1

AMG-Tie2-1 is an inhibitor of tunica interna endothelial cell kinase 2 (Tie2) and VEGF receptor 2 (VEGFR2) with IC50 values of 1 and 3 nM, respectively.

  • CAS Number: 870223-96-4
  • MF: C25H20F3N5O2
  • MW: 479.454
  • Catalog: VEGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Imatinib D8

Imatinib D8 (STI571 D8) is a deuterium labeled Imatinib (STI571). Imatinib is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, v-Abl, PDGFR and c-kit kinase activity[1][2].

  • CAS Number: 1092942-82-9
  • MF: C29H23D8N7O
  • MW: 501.65200
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 96-100 °C
  • Flash Point: N/A

BMS-986195

BMS-986195 is a potent, covalent, irreversible inhibitor of Bruton’s tyrosine kinase (BTK), with an IC50 of <1 nM.

  • CAS Number: 1912445-55-6
  • MF: C20H23FN4O2
  • MW: 370.4284
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Terevalefim

Terevalefim (ANG-3777), an hepatocyte growth factor (HGF) mimetic, selectively activates the c-Met receptor[1][2].

  • CAS Number: 1070881-42-3
  • MF: C9H8N2S
  • MW: 176.24
  • Catalog: c-Met/HGFR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 288.0±29.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 128.0±24.3 °C

VEGFR-2-IN-28

VEGFR-2-IN-28 (compound 12c) is a potent VEGFR-2 inhibitor with IC50 value of 0.83 µM. VEGFR-2-IN-28 induces apoptosis and has anticancer activity[1].

  • CAS Number: 2447597-39-7
  • MF: C26H17N7O7
  • MW: 539.46
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c-Fms-IN-14

c-Fms-IN-14 (Example 76) is a c-Fms inhibitor with an IC50 value of 4 nM. c-Fms-IN-14 can be used for research of cancer and autoimmune diseases[1].

  • CAS Number: 1898210-99-5
  • MF: C26H24N6O
  • MW: 436.51
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTK-IN-22

BTK-IN-22 is a BTK inhibitor (IC50: 0.9 nM). BTK-IN-22 also inhibits BLX and BMX with IC50s of 1.4 and 1.2 nM respectively. BTK-IN-22 shows improved kinase selectivity compared to Ibrutinib (HY-10997)[1]

  • CAS Number: 2573048-10-7
  • MF: C26H26N6O2
  • MW: 454.52
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PTC299

PTC299 is a dihydroorotate dehydrogenase (DHODH) inhibitor, has broad and potent activity against hematological cancer cells[1]. PTC299, also an orally bioavailable VEGF inhibitor, acts through posttranscriptional regulation of VEGF mRNA under conditions of cellular stress[2].

  • CAS Number: 1256565-36-2
  • MF: C25H20Cl2N2O3
  • MW: 467.34
  • Catalog: VEGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrosine kinase-IN-7

Tyrosine kinase-IN-7 (compound 13h) is an inhibitor of the tyrosine kinase EGFR. The IC50s for inhibiting EGFR(WT) and EGFR(T790M) are 0.630 μM and 0.956 μM respectively. Tyrosine kinase-IN-7 has antitumor activity against four cancer cell lines (HepG2, HCT-116, MCF-7, and A431) with IC50s of 13.02 μM, 10.14 μM, 12.68 μM, and 47.05 μM, respectively[1].

  • CAS Number: 345615-74-9
  • MF: C16H15N3OS
  • MW: 297.375
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 525.2±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.5±28.7 °C

PP2 (AG 1879)

PP2 is a reversible and ATP-competitive Src family kinases inhibitor with IC50s of 4 and 5 nM for Lck and Fyn, respectively.

  • CAS Number: 172889-27-9
  • MF: C15H16ClN5
  • MW: 301.774
  • Catalog: Src
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 493.5±40.0 °C at 760 mmHg
  • Melting Point: 214-216ºC
  • Flash Point: 252.3±27.3 °C

FGFR3-IN-2

FGFR3-IN-2 (compound 18b) is a potent and selective FGFR3 inhibitor, with IC50s of 4.1 nM and 570 nM for FGFR3 and VEGFR2, respectively. FGFR3-IN-2 can be used for the research of bladder cancer[1].

  • CAS Number: 2428742-58-7
  • MF: C28H39N9O4S
  • MW: 597.73
  • Catalog: FGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nilotinib monohydrochloride monohydrate

Nilotinib monohydrochloride monohydrate is a second generation tyrosine kinase inhibitor (TKI), is significantly more potent against BCR-ABL than Imatinib, and is active against many Imatinib-resistant BCR-ABL mutants.

  • CAS Number: 923288-90-8
  • MF: C28H25ClF3N7O2
  • MW: 583.992
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

KTX-955

KTX-955 is a potent IRAK4 degrader with DC50 values of 5 nM and 130 nM for IRAK4 and Ikaros, respectively. KTX-955 can be used to research anticancer[1][2].

  • CAS Number: 2573302-50-6
  • MF: C46H51F3N8O7
  • MW: 884.94
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CA-4948

CA-4948 is a selective and potent IRAK4 inhibitor.

  • CAS Number: 1801343-74-7
  • MF: C21H19N7O3
  • MW: 417.42
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A