The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by cytokine receptors, a superfamily of more than 30 transmembrane proteins that recognize specific cytokines, and is critical in blood formation and immune response. Canonical JAK/STAT signaling begins with the association of cytokines and their corresponding transmembrane receptors. Activated JAKs then phosphorylate latent STAT monomers, leading to dimerization, nuclear translocation, and DNA binding. In mammals, there are four JAKs (JAK1, JAK2, JAK3, TYK2) and seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6).

JAKs are an integral component of the receptor subunit with very little release or exchange into the cytoplasm and as such are located primarily at the plasma membrane. STAT has seven conserved features: an N-terminal domain (NT), a coiled-coil domain (CC), a central DNA-binding domain (DBD), a linker region, an SH2 domain followed by a single conserved tyrosine residue, and a C-terminal transactivation domain (TAD). JAK phosphorylation of the STAT proteins then results in a spatial reorganisation of the dimer complex, and translocates to the nucleus. Once in the nucleus, STAT dimmers are stabilised by NT:NT interactions and bind cooperatively to tandem sequence elements within promoter regions to activate the transcription of specific gene subsets.

Aberrant activation of the JAK/STAT pathway has been reported in a variety of diseases, including inflammatory conditions, hematologic malignancies, and solid tumors. More recently, human myeloproliferative neoplasms are discovered to be associated with a unique acquired somatic mutation in JAK2 (JAK2 V617F), rare exon 12 JAK2 mutations, or thrombopoietin receptor mutations that constitutively activate wild-type JAK2. As a result, several drug companies have begun to develop therapeutics that inhibit the function of JAK tyrosine kinases. Currently, several JAK-targeting drugs have been used in the clinic for treating diseases including rheumatoid arthritis and myeloproliferative.

References:
[1] Kiu H, et al. Growth Factors. 2012 Apr;30(2):88-106.
[2] Quintás-Cardama A, et al. Clin Cancer Res. 2013 Apr 15;19(8):1933-40.
[3] Villarino AV, et al. J Immunol. 2015 Jan 1;194(1):21-7.
[4] Vainchenker W, et al. Oncogene. 2013 May 23;32(21):2601-13.


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(1E)-4-Isothiocyanato-1-(methylsulfinyl)-1-butene

Sulforaphene, isolated from radish seeds, exhibits an ED50 against velvetleaf seedlings approximately 2 x 10-4 M. Sulforaphene promotes cancer cells apoptosis and inhibits migration via inhibiting EGFR, p-ERK1/2, NF‐κB and other signals[1][2][3][4].

  • CAS Number: 592-95-0
  • MF: C6H9NOS2
  • MW: 175.272
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 362.2±42.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 172.8±27.9 °C

CGP 52411

CGP52411 (DAPH) is a high selective, potent, orally active and ATP-competitive EGFR inhibitor with an IC50 of 0.3 μM. CGP52411 blocks the toxic influx of Ca2+ ions into neuronal cells, and dramatic inhibits and reverses the formation of β-amyloid (Aβ42) fibril aggregates associated with Alzheimer's disease[1][2].

  • CAS Number: 145915-58-8
  • MF: C20H15N3O2
  • MW: 329.35200
  • Catalog: EGFR
  • Density: 1.374 g/cm3
  • Boiling Point: N/A
  • Melting Point: 199-202℃
  • Flash Point: N/A

Benzyl-amp

IST5-002, a potent Stat5a/b inhibitor, selectively inhibits transcriptional activity of Stat5a/b (IC50s: 1.5 μM for Stat5a, 3.5 μM for Stat5b). IST5-002 inducs cell apoptotic and death of prostate cancer cells and chronic myeloid leukemia (CML) cells. IST5-002 can be used in the research of prostate cancer and chronic myeloid leukemia (CML)[1].

  • CAS Number: 13484-66-7
  • MF: C17H20N5O7P
  • MW: 437.34400
  • Catalog: Apoptosis
  • Density: 1.81g/cm3
  • Boiling Point: 798.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 436.7ºC

HX103

HX103 is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-based fluorogenic probe. HX103 inhibits EGFR 19 del, EGFR L858R, EGFR wild type and EGFR T790M with IC50s of 1.3, 1.5, 4.0 and 977 nM, respectively. HX103 can be used for quantifying active-EGFR to predict drug sensitivity in NSCLC patients with EGFR-activating mutations[1].

  • CAS Number: 2566466-98-4
  • MF: C26H25ClFN7O5S
  • MW: 602.04
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Delphinidin chloride

Delphinidin chloride, an anthocyanidin, is isolated from berries and red wine. Delphinidin chloride shows endothelium-dependent vasorelaxation. Delphinidin chloride also can modulate JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells[1][2][3].

  • CAS Number: 528-53-0
  • MF: C15H11ClO7
  • MW: 338.697
  • Catalog: Apoptosis
  • Density: 1.3946 (rough estimate)
  • Boiling Point: 454.94°C (rough estimate)
  • Melting Point: >350ºC
  • Flash Point: N/A

STAT3-SH2 domain inhibitor 1

STAT3-SH2 domain inhibitor 1 is a potent Src Homology 2 (SH2) Domain of STAT3 (STAT3-SH2 domain) inhibitor with a Kd value of 1.57 μM. STAT3-SH2 domain inhibitor 1 inhibits STAT3 signaling transduction and transcriptional activation. STAT3-SH2 domain inhibitor 1 induces apoptosis in gastric cancer cells. STAT3-SH2 domain inhibitor 1 can be used in research of cancer[1].

  • CAS Number: 2816059-41-1
  • MF: C28H28BF5N2O5S
  • MW: 610.40
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Dacomitinib (PF-00299804)

Dacomitinib is a specific and irreversible inhibitor of the ERBB family of kinases with IC50s of 6 nM, 45.7 nM and 73.7 nM for EGFR, ERBB2, and ERBB4, respectively.

  • CAS Number: 1110813-31-4
  • MF: C24H25ClFN5O2
  • MW: 469.939
  • Catalog: EGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 665.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 356.4±31.5 °C

PDZ1i

PDZ1i (113B7) is a specific inhibitor of MDA-9/Syntenin activity that inhibits MDA-9/Syntenin binding to EGFRvIII; selectively binds with micromolar affinity to the PDZ1 domain of MDA-9/Syntenin, with no affinity for PDZ2 domain of MDA-9/Syntenin; reduces invasion gains in GBM cells following radiation, inhibits crucial GBM signaling involving FAK and mutant EGFR, EGFRvIII, and abrogated gains in secreted proteases, MMP-2 and MMP-9, following radiation; results in smaller, less invasive tumors and enhanced survival in an in vivo glioma model.

  • CAS Number: 2083618-79-3
  • MF: C28H26N8O
  • MW: 538.568
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zalutumumab

Zalutumumab is a high affinity, completely human IgG1 monoclonal antibody targeting EGFR. Zalutumumab binds to domain III of the EGF receptor and acts by blocking the binding of EGF and by sterically interfering with the active conformation of the receptor. Zalutumumab binds with IgG and its Fab fragment with EC50s of 7 and 19 nM, respectively. Zalutumumab can be used for the research of cancer[1][2][3].

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

Lorpucitinib

Lorpucitinib is a Gut-Restricted JAK Inhibitor for the research of Inflammatory Bowel Disease[1].

  • CAS Number: 2230282-02-5
  • MF: C22H28N6O2
  • MW: 408.50
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pertuzumab

Pertuzumab (PBS), a humanized monoclonal antibody, is a HER2 dimerization inhibitor for the treatment of metastatic HER2-positive breast cancer.

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

Ubiquinone Q0

Coenzyme Q0 (CoQ0) is a potent, oral active ubiquinone compound can be derived from Antrodia cinnamomea. Coenzyme Q0 induces apoptosis and autophagy, suppresses of HER-2/AKT/mTOR signaling to potentiate the apoptosis and autophagy mechanisms. Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of inflammation and redox imbalance. Coenzyme Q0 has anti-angiogenic activity through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling[1][2][3].

  • CAS Number: 605-94-7
  • MF: C9H10O4
  • MW: 182.173
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 331.4±42.0 °C at 760 mmHg
  • Melting Point: 58-60 °C(lit.)
  • Flash Point: 148.6±27.9 °C

4H-Pyran-4-one,2,6-bis(4-methoxyphenyl)-

NSC81111 is a potent and orally active EGFR-TK inhibitor with an IC50 of 0.15 nM. NSC81111 has anticaner effects[1].

  • CAS Number: 1678-14-4
  • MF: C19H16O4
  • MW: 308.32800
  • Catalog: EGFR
  • Density: 1.218g/cm3
  • Boiling Point: 528.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 235.1ºC

8α-Tigloyloxyhirsutinolide 13-O-acetate

8α-Tigloyloxyhirsutinolide 13-O-acetate is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and Pyroptosis, and late DNA damage, cell cycle arrest, Apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo[1][2].

  • CAS Number: 83182-58-5
  • MF: C22H28O8
  • MW: 420.453
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 589.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 201.4±23.6 °C

CHZ868

CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.

  • CAS Number: 1895895-38-1
  • MF: C22H19F2N5O2
  • MW: 423.415
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Futuximab

Futuximab is a chimeric monoclonal antibody targeting non-overlapping epitopes on EGFR. Futuximab has antineoplastic activity[1].

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

pimozide

Pimozide is a dopamine receptor antagonist, with Kis of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a Ki of 39 nM; Pimozide also inhibits STAT3 and STAT5.

  • CAS Number: 2062-78-4
  • MF: C28H29F2N3O
  • MW: 461.546
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 649.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.3±34.3 °C

TAS0728

TAS0728 is a potent, selective, oral active, irreversible and covalent-binding HER2 inhibitor, binds to HER2 at C805, inhibits its kinase activity, with an IC50 of 13 nM. TAS0728 shows IC50s of 4.9, 8.5, 31, 65, 33, 25, 86 and 36 nM for BMX, HER4, BLK, EGFR, JAK3, SLK, LOK and human HER2, respectively. TAS0728 also inhibits the phosphorylation of HER2, HER3, and downstream effectors, shows no obvious effect on EGFR. Antitumor activity[1].

  • CAS Number: 2088323-16-2
  • MF: C26H32N8O3
  • MW: 504.58
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK1/TYK2-IN-1

JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 (IC50 = 29 and 41 nM respectively).

  • CAS Number: 1883300-48-8
  • MF: C18H20F3N7O
  • MW: 407.39
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Niclosamide

Niclosamide is an inhibitor of STAT3 with IC50 of 0.25 μM in HeLa cells and inhibits DNA replication in a cell-free assay.

  • CAS Number: 50-65-7
  • MF: C13H8Cl2N2O4
  • MW: 327.120
  • Catalog: STAT
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 424.5±45.0 °C at 760 mmHg
  • Melting Point: 225-230ºC
  • Flash Point: 210.5±28.7 °C

Gefitinib D8

Gefitinib D8 (ZD1839 D8) is a deuterium labeled Gefitinib. Gefitinib is an EGFR tyrosine kinase inhibitor, with IC50 of 2-37 nM in NR6wtEGFR cells[1][2].

  • CAS Number: 857091-32-8
  • MF: C22H16D8ClFN4O3
  • MW: 454.95200
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Povorcitinib

Povorcitinib is a potent and selective inhibitor of JAK1. Povorcitinib has the potential for the research of disease selected from cutaneous lupus erythematosus (CLE) and Lichen planus (LP) (extracted from patent WO2021076124A1)[1].

  • CAS Number: 1637677-22-5
  • MF: C23H22F5N7O
  • MW: 507.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-00299804

Dacomitinib (PF-00299804) hydrate is an orally active, irreversible pan-ErbB inhibitor. Dacomitinib hydrate can be used in the research of cancers such as metastatic non-small cell lung cancer (NSCLC)[1].

  • CAS Number: 1042385-75-0
  • MF: C24H27ClFN5O3
  • MW: 487.95
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-56

EGFR-IN-56 (Compound 13a) is a potent EGFR inhibitor with IC50 values of 541.7 nM and 132.1 nM against EGFRT790M and EGFRT790M/L858R, respectively. EGFR-IN-56 blocks cancer cells in G2/M phase and induce into late apoptosis[1].

  • CAS Number: 2477726-83-1
  • MF: C23H22N4O3S
  • MW: 434.51
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Protosappanin A

Protosappanin A (PTA), an immunosuppressive ingredient and major biphenyl compound isolated from Caesalpinia sappan L, suppresses JAK2/STAT3-dependent inflammation pathway through down-regulating the phosphorylation of JAK2 and STAT3[1].

  • CAS Number: 102036-28-2
  • MF: C15H12O5
  • MW: 272.25
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 613.1±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 238.8±25.0 °C

STAT3-IN-1

STAT3-IN-1 (compound 7d) is an excellent, selective and orally active STAT3 inhibitor, with IC50 values of 1.82 μM and 2.14 μM in HT29 and MDA-MB 231 cells, respectively. STAT3-IN-1 (compound 7d) induces tumor apoptosis[1].

  • CAS Number: 2059952-75-7
  • MF: C28H29NO6
  • MW: 475.53
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT5-IN-1

STAT5-IN-1 is a STAT5 inhibitor with an IC50 of 47 μM for STAT5β isoform.

  • CAS Number: 285986-31-4
  • MF: C16H11N3O3
  • MW: 293.277
  • Catalog: STAT
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HER2-IN-14

HER2-IN-14 (Compound 34) is an HER2 inhibitor with an IC50 of 18 nM. HER2-IN-14 also inhibits wt-EGFR with an IC50 of 6.3 μM[1].

  • CAS Number: 2414056-35-0
  • MF: C26H23ClF2N8O3
  • MW: 568.96
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momelotinib-d10

Momelotinib-d10 (CYT387-d10) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally active and ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively, shows much less activity against JAK3[1][2].

  • CAS Number: 1619927-69-3
  • MF: C23H12D10N6O2
  • MW: 424.52
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Minecoside

Minecoside is a CXCR4/STAT3 inhibitor with anticancer and anti-inflammatory activity. Minecoside decreases CXCR4 expression and suppresses STAT3 activation, thus to inhibit CXCL 12-induced invasion. Minecoside potently inhibits cancer metastasis and promotes apoptotic progression[1][2].

  • CAS Number: 51005-44-8
  • MF: C25H30O13
  • MW: 538.50
  • Catalog: CXCR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 815.9±65.0 °C at 760 mmHg
  • Melting Point: 142℃
  • Flash Point: 275.7±27.8 °C