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.


Anti-infection >
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EGFR/HER2/CDK9-IN-2

EGFR/HER2/CDK9-IN-2 (Compound 9) is a potent inhibitor of EGFR/HER2/CDK9 with IC50s of 145.35, 129.07, and 117.13 nM, respectively. EGFR/HER2/CDK9-IN-2 exhibits remarkable antitumor activity[1].

  • CAS Number: 1180924-34-8
  • MF: C23H20N4O5S2
  • MW: 496.56
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Khellin

Khellin, a naturally occurring furochromone, is an EGFR inhibitor with an IC50 of 0.15 µM. Khelline has anti-proliferative activity in vitro. Khellin has antispasmodic and coronary vasodilator effects[1][2].

  • CAS Number: 82-02-0
  • MF: C14H12O5
  • MW: 260.242
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 482.1±0.0 °C at 760 mmHg
  • Melting Point: 150-154ºC
  • Flash Point: 218.8±28.7 °C

Ascochlorin

Ascochlorin (Ilicicolin D), an isoprenoid antibiotic, mediates its anti-tumor effects predominantly through the suppression of STAT3 signaling cascade. Ascochlorin induces apoptosis. Anti-inflammatory activity[1][2][3].

  • CAS Number: 26166-39-2
  • MF: C23H29ClO4
  • MW: 404.92700
  • Catalog: Apoptosis
  • Density: 1.199g/cm3
  • Boiling Point: 556.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 290.6ºC

EGFR-IN-46

EGFR-IN-46 is a potent EGFR and FAK dual inhibitor with IC50s of 20.17 nM, 14.25 nM, respectively. EGFR-IN-46 significantly inhibits the growth of cancer cells. EGFR-IN-46 induces cell apoptosis[1].

  • CAS Number: 2764772-88-3
  • MF: C27H32F3N3O3
  • MW: 503.56
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thi-DPPY

Thi-DPPY (compound 8e) is a potent and orally active JAK3 inhibitor with IC50 values of 62.4, 1.38 nM for BTK, JAK, respectively. Thi-DPPY shows anti-proliferative activity against HBE cells. Thi-DPPY shows anti-inflammatory activity in vivo. Thi-DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].

  • CAS Number: 2307699-34-7
  • MF: C28H28ClN5O4S
  • MW: 566.07
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LFM-A13

LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC50s of 2.5 μM, 10 μM and 61 μM. LFM-A13 has antiproliferative activity and anticancer activity. LFM-A13 can be used in cancer-related research[1][3][4]

  • CAS Number: 62004-35-7
  • MF: C11H8Br2N2O2
  • MW: 360.00
  • Catalog: Polo-like Kinase (PLK)
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 487.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.9±28.7 °C

3,3',4',5,6,7-HEXAHYDROXYFLAVONE

Quercetagetin (6-Hydroxyquercetin) is the major flavonoid isolated from Citrus unshiu (C. unshiu) peel[3]. Quercetagetin is a moderately potent and selective, cell-permeable pim-1 kinase inhibitor (IC50, 0.34 μM)[1]. Anti-inflammatory and anticancer properties.

  • CAS Number: 90-18-6
  • MF: C15H10O8
  • MW: 318.23500
  • Catalog: Pim
  • Density: 1.912 g/cm3
  • Boiling Point: 732.4ºC at 760 mmHg
  • Melting Point: >300ºC
  • Flash Point: 280.3ºC

Furowanin A

Furowanin A is a flavonoid with anti-neoplastic effects. Furowanin A inhibits STAT3/Mcl-1 axis to suppress proliferation, block cell cycle progression, induce apoptosis and promote autophagy. Furowanin A potently inhibits colorectal cancer (CRC) cells[1].

  • CAS Number: 911004-72-3
  • MF: C25H26O7
  • MW: 438.47
  • Catalog: Bcl-2 Family
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 697.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.3±25.0 °C

EGFR/HER2-IN-9

EGFR/HER2-IN-9 (Compound 1) is an EGFR and HER2 inhibitor with IC50s of 3.2, 8.3 and 14 nM against EGFR, EGFR T790M and HER2, respectively[1].

  • CAS Number: 1637253-79-2
  • MF: C25H25ClFN5O4
  • MW: 513.95
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT3 inhibitor C188

A potent, selective STAT3 inhibitor that blocks STAT3 binding to its phosphopeptide ligand (IC50=20 uM) and inhibits IL-6-mediated phosphorylation of STAT3; inhibits nuclear translocation of phosphorylated Stat3 with IC50 of 39 uM, induces apoptosis preferentially of breast cancer cell lines with constitutive Stat3 activation.

  • CAS Number: 823828-18-8
  • MF: C19H15NO7S2
  • MW: 433.449
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Scutellarin

Scutellarin, an active flavone isolated from Scutellaria baicalensis, can down-regulates the STAT3/Girdin/Akt signaling in HCC cells, and inhibits RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts.

  • CAS Number: 27740-01-8
  • MF: C21H18O12
  • MW: 462.360
  • Catalog: STAT
  • Density: 1.8±0.1 g/cm3
  • Boiling Point: 891.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 314.9±27.8 °C

GDC-4379

GDC-4379 is a JAK1 inhibitor that can be used for the research of asthma[1].

  • CAS Number: 2252277-73-7
  • MF: C21H18ClF2N7O3
  • MW: 489.86
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DTP3

DTP3 TFA is a potent and selective GADD45β/MKK7 inhibitor. DTP3 TFA targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway[1].

  • CAS Number: 1809784-29-9
  • MF: C26H35N7O5
  • MW: 525.600
  • Catalog: DNA/RNA Synthesis
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Angoline

Angoline is a potent and selective IL6/STAT3 signaling pathway inhibitor with an IC50 of 11.56 μM. Angoline inhibits STAT3 phosphorylation and its target gene expression, and inhibits cancer cell proliferation[1].

  • CAS Number: 21080-31-9
  • MF: C22H21NO5
  • MW: 379.40600
  • Catalog: STAT
  • Density: 1.36g/cm3
  • Boiling Point: 555.5ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 164.1ºC

Eflepedocokin alfa

Eflepedocokin alfa is a recombinant fusion protein with potential cell protective activity. Eflepedocokin alfa consists of human IL-22 fused to human IgG2-Fc domain. Eflepedocokin alfa leads to the activation of IL-22/IL-22R-mediated signal transduction pathways as well as STAT3. Eflepedocokin alfa plays a role in immune response and bacterial infection, enhancing intestinal barrier function, intestinal immunity, and tissue repair[1].

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

JAK-IN-27

JAK-IN-27 (compound 1) is an orally active and potent JAKS family kinase inhibitor with IC50s of 3.0 nM (TYK2), 7.7 nM (JAK1), 629.6 nM (JAK3), respectively. JAK-IN-27 inhibits IFN-α2B-induced phosphorylation of STAT3 in Jurkat cells (IC50=23.7 nM)[1].

  • CAS Number: 2673176-36-6
  • MF: C20H21F2N7O
  • MW: 413.42
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/BRAFV600E-IN-1

EGFR/BRAFV600E-IN-1 (Compound 23) is a potent EGFR and BRAFV600E dual inhibitor with IC50s of 0.08 and 0.15 µM, respectively. EGFR/BRAFV600E-IN-1 induces apoptosis and cell cycle arrest in both pre-G1 and G2/M phases. EGFR/BRAFV600E-IN-1 exhibits antiproliferative activity againist A-549, MCF-7, Panc-1, HT-29 with IC50s of 1.2, 0.79, 1.3, and 1.23 µM, respectively[1].

  • CAS Number: 2492429-45-3
  • MF: C24H24ClN3O3
  • MW: 437.92
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

R8-T198wt

R8-T198wt is a cell-permeable peptide inhibitor of Pim-1 kinase, derived from p27Kip1. R8-T198wt inhibits Pim-1 phosphorylation of p27Kip1 and Bad; induces cell cycle arrest (at G1) and apoptosis in DU145 prostate cancer cells. R8-T198wt also inhibits Pim-1-dependent growth of DU145 cells in vitro and in vivo. R8-T198wt displays no effect on the growth of normal prostate epithelial RPWE-1 cells at concentrations of 10 and 20 μM.

  • CAS Number: 2305815-72-7
  • MF: C111H211N59O26S
  • MW: 2820.33
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neocucurbitacin A

Neocucurbitacin A (compound 7) is STAT3 inhibitor a compound extracted from Aquilaria crassna pericarp. Neocucurbitacin A can be used for anticancer research[1].

  • CAS Number: 352359-53-6
  • MF: C31H42O8
  • MW: 542.66
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SHR0302

SHR0302 is a potent and orally active all members of the JAK family inhibitor, particularly JAK1. The selectivity of SHR0302 for JAK1 is >10-fold for JAK2, 77-fold for JAK3, 420-fold for Tyk2. SHR0302 inhibits JAK1-STAT3 phosphorylation and induces the apoptosis of hepatic stellate cells. SHR0302 has anti-proliferative and anti-inflammatory effects[1][2].

  • CAS Number: 1445987-21-2
  • MF: C18H22N8O2S
  • MW: 414.48
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Erlotinib

Erlotinib is a medication for the treatment of non-small cell lung cancer. It inhibits purified EGFR kinase with an IC50 of 2 nM.

  • CAS Number: 183321-74-6
  • MF: C22H23N3O4
  • MW: 393.436
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 553.6±50.0 °C at 760 mmHg
  • Melting Point: 223 - 228ºC
  • Flash Point: 288.6±30.1 °C

JAK-IN-14

JAK-IN-14 is a potent and selective JAK1 inhibitor, with an IC50 of <5 μM. JAK-IN-14 is >8-fold more selective for JAK1 than JAK2 and JAK3 (Patent WO2016119700A1, compound 16)[1].

  • CAS Number: 1973485-06-1
  • MF: C19H15FN4O
  • MW: 334.35
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT6-IN-3

STAT6-IN-3 (Compound 18a) is a STAT6 inhibitor (IC50= 44 nM). STAT6-IN-3 targets the Src Homology 2 (SH2) domain of STAT6. STAT6-IN-3 can be used for research of inflammation such as asthma[1].

  • CAS Number: 371919-80-1
  • MF: C32H35IN3O7P
  • MW: 731.51
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zorifertinib hydrochloride

Zorifertinib (AZD3759) hydrochloride is a potent, orally active, central nervous system-penetrant, EGFR inhibitor (IC50s: 0.3, 0.2, and 0.2 nM for EGFRwt, EGFRL858R, and EGFRexon 19Del, respectively). Zorifertinib hydrochloride induces cancer cell apoptosis. Zorifertinib hydrochloride has antitumor activity, and can be used for NSCLC, HCC etc. research[1][2].

  • CAS Number: 1626387-81-2
  • MF: C22H24Cl2FN5O3
  • MW: 496.362
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-5

JAK3/BTK-IN-5 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-5 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147953A1, compound 35)[1]

  • CAS Number: 2673196-75-1
  • MF: C19H22ClN7O2
  • MW: 415.88
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-52

EGFR-IN-52 (Compound 4) is a potent EGFR inhibitor with IC50 values of 0.358, 86.02 and 432.67 µM against EGFR, EGFR L858R-TK and EGFR T790M-TK, respectively. EGFR-IN-52 shows cytotoxic activity against cancer cell lines and induces apoptosis[1].

  • CAS Number: 454436-75-0
  • MF: C19H18N4O3S
  • MW: 382.44
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-7

Tyk2-IN-7 (Compound 48) is a TYK2 JH2 inhibitor, binds to TYK2 JH2 domain with IC50 and Ki.app of 0.00053 μM and 0.00007 μM, respectively. Tyk2-IN-7 (Compound 48) provides a highly selective alternative to conventional TYK2 orthosteric inhibitors, inhibits TYK2/JAK1/JAK2 kinase domain. Tyk2-IN-7 (Compound 48) provides robust inhibition in a mouse IL-12-induced IFNγ pharmacodynamic model as well as efficacy in an IL-23 and IL-12-dependent mouse colitis model[1].

  • CAS Number: 1609391-90-3
  • MF: C18H15D3N6O3S
  • MW: 401.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Garcinone D

Garcinone D, a natural xanthone from mangosteen, promotes the proliferation of C17.2 neural stem cell. Garcinone D increases the protein levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), Cyclin D1 and nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1) in concentration- and time- dependent manners[1].

  • CAS Number: 107390-08-9
  • MF: C24H28O7
  • MW: 428.475
  • Catalog: STAT
  • Density: 1.304
  • Boiling Point: 674.2±55.0 °C at 760 mmHg
  • Melting Point: 202-204 ºC
  • Flash Point: 231.2±25.0 °C

resveratrol triacetate

Triacetylresveratrol, an acetylated analog of Resveratrol. Triacetylresveratrol decreases the phosphorylation of STAT3 and NF-κB in a dose- and time- dependent manner in PANC-1 and BxPC-3 cells. Anticancer effects[1].

  • CAS Number: 42206-94-0
  • MF: C20H18O6
  • MW: 354.353
  • Catalog: STAT
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 504.8±50.0 °C at 760 mmHg
  • Melting Point: 117.0 to 121.0 °C
  • Flash Point: 221.4±30.2 °C

JAK-IN-15

JAK-IN-15 is a JAK inhibitor. WO2016119700A1 (Compound 15)[1].

  • CAS Number: 1973485-05-0
  • MF: C22H23FN4O3S
  • MW: 442.51
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A