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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R788 (disodium hexahydrate)

Fostamatinib disodium hexahydrate (R788 disodium hexahydrate), a prodrug of the active metabolite R406, is a potent Syk inhibitor with IC50 of 41 nM.

  • CAS Number: 914295-16-2
  • MF: C23H24FN6Na2O9P.6H2O
  • MW: 732.51
  • Catalog: Syk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rp-8-CPT-cAMPS

Rp-8-CPT-cAMPS, a cAMP analog, is a potent and competitive antagonist of cAMP-induced activation of cAMP-dependent PKA I and II. Rp-8-CPT-cAMPS preferentially selects site A of RI compares to site A of RII and site B of RII compares to site B of RI[1][2].

  • CAS Number: 129735-01-9
  • MF: C16H14ClN5NaO5PS2
  • MW: 509.85900
  • Catalog: PKA
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Vofatamab

Vofatamab (B-701) is an anti-FGFR3 monoclonal antibody (mAb). Vofatamab blocks activation of both the wildtype and genetically activated receptor. Vofatamab can be used in the research of metastatic urothelial carcinoma (mUC)[1].

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

Syk-IN-1

Syk-IN-1 (compound 4) is a potent Syk inhibitor, with an IC50 of 35 nM[1].

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

Capmatinib (INCB28060)

Capmatinib (INCB28060) is a potent and selective c-MET kinase inhibitor. Capmatinib (INCB28060) inhibits c-MET kinase activity with an average IC50 of 0.13 nM.

  • CAS Number: 1029712-80-8
  • MF: C23H17FN6O
  • MW: 412.419
  • Catalog: c-Met/HGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTK inhibitor 10

BTK-030 is a novel BTK inhibitor.

  • CAS Number: 2241732-30-7
  • MF: C25H23N5O3
  • MW: 441.491
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-69

EGFR-IN-69 (compound 17g) is a potent EGFR inhibitor, with IC50 values of 4.3, 6.6 and 25.6 nM against EGFRL858R/T790M/C797S, EGFRL858R/T790M, and EGFR19del/T790M/C797S, respectively. EGFR-IN-69 can be used for non-small-cell-lung-cancer (NSCLC) research[1].

  • CAS Number: 2433837-65-9
  • MF: C31H37Cl2N7O3S
  • MW: 658.64
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IRAK4-IN-1

IRAK4-IN-1 is an interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor with an IC50 of 7 nM.

  • CAS Number: 1820787-94-7
  • MF: C19H23N5O
  • MW: 337.42
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Seribantumab

Seribantumab (MM 121) is a fully human IgG2 monoclonal antibody that targets HER3. Seribantumab blocks the activation of epidermal growth factor receptor (ErbB) family members and its downstream signal. Seribantumab inhibits neuregulin 1 (NRG1) fusion-dependent tumorigenesis in vitro and in vivo in breast, lung and ovarian patient-derived cancer models[1].

  • CAS Number: 1334296-12-6
  • MF:
  • MW: 143.2 (kDa)
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY2784544

Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM.

  • CAS Number: 1229236-86-5
  • MF: C23H25ClFN7O
  • MW: 469.942
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SMAD3

SIS3 free base is a potent and selective inhibitor of TGF- beta1-induced Smad3 phosphorylation with an IC50 of 3 μM. SIS3 free base increases luciferase activity of p3TP-lux by abrogating the overexpression of constitutively active form of ALK-5[1].

  • CAS Number: 1009104-85-1
  • MF: C28H27N3O3
  • MW: 453.532
  • Catalog: ALK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 721.8±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 390.3±32.9 °C

BTK-IN-14

BTK-IN-14 is a potent inhibitor of BTK. BTK plays an important role in signaling mediated by B cell antigen receptor (BCR) and Fcγreceptor (FcγR) in B cells and myeloid cells, respectively. BTK-IN-14 has the potential for the research of related diseases, especially autoimmune diseases, inflammatory diseases or cancer (extracted from patent WO2022057894A1, compound 1)[1].

  • CAS Number: 2764674-60-2
  • MF: C38H44N8O4
  • MW: 676.81
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-05231023

PF-05231023, a long-acting fibroblast growth factor 21 (FGF21) analog, is a FGF21-receptor agonist, suitable for development as a potential treatment for T2DM[1][5].

  • CAS Number: 1037589-69-7
  • MF: C26H32N4O8
  • MW: 528.55
  • Catalog: PROTAC Linker
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Savolitinib

Savolitinib (AZD6094) ia highly potent and selective c-Met inhibitor with an IC50 of 5 nM.

  • CAS Number: 1313725-88-0
  • MF: C17H15N9
  • MW: 345.361
  • Catalog: c-Met/HGFR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JBJ-04-125-02

JBJ-04-125-02 is a potent, mutant-selective, allosteric and orally active EGFR inhibitor with an IC50 of 0.26 nM for EGFRL858R/T790M. JBJ-04-125-02 can inhibit cancer cell proliferation and EGFRL858R/T790M/C797S signaling. JBJ-04-125-02 has anti-tumor activities[1].

  • CAS Number: 2140807-05-0
  • MF: C29H26FN5O3S
  • MW: 543.61
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ASN-002

ASN-002 is a potent dual inhibitor of spleen tyrosine kinase (SYK) and janus kinase (JAK) with IC50 values of 5-46 nM.

  • CAS Number: 1425381-60-7
  • MF: C24H28N8O2
  • MW: 460.53
  • Catalog: Syk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c-Fms-IN-9

c-Fms-IN-9 is a c-FMS inhibitor extracted from patent WO2014145023A1, Compound Example 7. c-Fms-IN-9 inhibits unphosphorylated c-FMS kinase (uFMS) and uKIT with IC50s of <0.01 μM and 0.1-1 μM, respectively[1].

  • CAS Number: 1628574-50-4
  • MF: C21H23N7O2
  • MW: 405.45
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BTK inhibitor 19

BTK inhibitor 19 is a highly selective, covalent BTK inhibitor (IC50 = 2.7 nM).

  • CAS Number: 2557174-19-1
  • MF: C25H24F3N7O3
  • MW: 527.50
  • Catalog: Btk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GNE-4997

GNE-4997 is a potent and selective ITK/TSK inhibitor.

  • CAS Number: 1705602-02-3
  • MF: C25H27F2N5O3S
  • MW: 515.58
  • Catalog: Itk
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IRAK-1-4 Inhibitor I

IRAK-1-4 Inhibitor I is an inhibitor of interleukin-1 receptor-associated kinase 1/4 (IRAK 1/4) with IC50s of 0.2 μM and 0.3 μM, respectively.

  • CAS Number: 509093-47-4
  • MF: C20H21N5O4
  • MW: 395.41200
  • Catalog: IRAK
  • Density: 1.4
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EMI1

EMI1 is an EGFR ex19del/T790M/C797S and EGFR L858R/T790M/C797S inhibitor[1].

  • CAS Number: 35773-42-3
  • MF: C20H18N2O3
  • MW: 334.36900
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

squarunkin A

Squarunkin A is a potent and selective UNC119-cargo interaction inhibitor, interrupting the UNC119A-myristoylated Src N-terminal peptide interaction (IC50=10 nM). Squarunkin A interferes with the activation of Src kinase in cells[1].

  • CAS Number: 2101958-02-3
  • MF: C25H32F3N5O4
  • MW: 523.55
  • Catalog: Src
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TYRPHOSTIN AG 1290

Entacapone acid (Tyrphostin AG1290) is a tyrosine kinase inhibitor. Entacapone acid reduces hepatic protein synthesis rate (HPS) in vivo[1].

  • CAS Number: 160391-70-8
  • MF: C10H6N2O6
  • MW: 250.164
  • Catalog: c-Met/HGFR
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 478.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 243.4±28.7 °C

Selatinib

Selatinib is a reversible and orally active dual EGFR and ErbB2 inhibitor with IC50s of 13 nM and 22.5 nM, respectively. Selatinib has anticancer effects[1].

  • CAS Number: 1275595-86-2
  • MF: C29H26ClFN4O3S
  • MW: 565.06
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 740.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 401.6±32.9 °C

EMI56

EMI56, the derivative of EMI1, displays greater potency toward mutant EGFR than EMI1. EMI56 inhibits EGFR triple mutants[1].

  • CAS Number: 2414374-41-5
  • MF: C21H20N2O3
  • MW: 348.40
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

c-Fms-IN-8

c-Fms-IN-8 (compound 4a) is a colony stimulating factor-1 receptor (CSF-1R, c-FMS) Type II inhibitor, with an IC50 of 9.1 nM[1].

  • CAS Number: 1255303-58-2
  • MF: C27H30N2O5
  • MW: 462.54
  • Catalog: c-Fms
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sitravatinib malate

Sitravatinib malate (MGCD516 malate) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC50s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively[1]. Sitravatinib malate shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment[2].

  • CAS Number: 2244864-88-6
  • MF: C37H35F2N5O9S
  • MW: 763.76
  • Catalog: c-Kit
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JNK3 inhibitor-2

JNK3 inhibitor-2 is a potent and selective JNK3 inhibitor with IC50 values of >100, >100, 0.25 µM for JNK1, JNK2, JNK3, respectively. JNK3 inhibitor-2 shows DDR1 and EGFR (T790M, L858R) inhibition[1].

  • CAS Number: 2366264-18-6
  • MF: C20H14N2O2
  • MW: 314.34
  • Catalog: JNK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Brigatinib

Brigatinib is a highly potent and selective ALK inhibitor, with an IC50 of 0.6 nM.

  • CAS Number: 1197953-54-0
  • MF: C29H39ClN7O2P
  • MW: 584.092
  • Catalog: ALK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 781.8±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 426.6±35.7 °C

Conbercept

Conbercept (KH902) is a monoclonal antibody targeting VEGFRA fused to the IGHG1 Fc fragment. Conbercept is produced by the fusion of the second C-LIKE of FLT1 and the third and fourth C-LIKE of KDR with IGHG1 Fc. Conbercept[1].

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