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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EGFR-IN-64

EGFR-IN-64 (Compound 3c) is a potent EGFR inhibitor with an IC50 of 0.33 μM. EGFR-IN-64 shows anticancer activity[1].

  • CAS Number: 2416924-93-9
  • MF: C20H21N3O3
  • MW: 351.40
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

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

XZH-5

XZH-5 is a small moelcule that inhibits constitutive and interleukin-6-induced STAT3 phosphorylation, inhibits STAT3 DNA binding ability and downregulation of STAT3 downstream genes; inhibits downregulation of STAT3 downstream genes, such as Bcl-2, Bcl-xL, Cyclin D1 and Survivin, demonstrates blockade of STAT3 phosphorylation in human rhabdomyosarcoma cells with apoptosis and suppresses colony-forming ability and cell migration; blocks IL-6-induced STAT3 phosphorylation and nuclear translocation but not the stimulation of STAT1 phosphorylation by IFN-γ.

  • CAS Number: 1360562-98-6
  • MF: C22H25F6N5O4
  • MW: 537.463
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC STAT3 degrader-2

PROTAC STAT3 degrader-2 is a selective and efficacious PROTAC degrader of STAT3 protein with a DC50 of 3.54 μM in Molm-16 Cell. PROTAC STAT3 degrader-2 has the potential for cancer research[1].

  • CAS Number: 2429877-78-9
  • MF: C59H60F2N9O13P
  • MW: 1172.13
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Lumretuzumab

Lumretuzumab (Anti-Human ERBB3 Recombinant Antibody) is a humanized anti-HER3 monoclonal antibody that can be used for the research of cancer[1].

  • 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

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

TCS-PIM-1-4a

TCS-PIM-1-4a is a Pim inhibitor that blocks mTORC1 activity via activation of AMPK; kills a wide range of both myeloid and lymphoid cell lines (with IC50 values ranging from 0.8 to 40 μM).IC50 value:Target: Pim SMI-4a a novel benzylidene-thiazolidine-2, 4-dione small molecule inhibitor of the Pim kinases, kills a wide range of both myeloid and lymphoid cell lines with precursor T-cell lymphoblastic leukemia/lymphoma (pre-T-LBL/T-ALL) being highly sensitive. Incubation of pre-T-LBL cells with SMI-4a induced G1 phase cell-cycle arrest secondary to a dose-dependent induction of p27(Kip1), apoptosis through the mitochondrial pathway, and inhibition of the mammalian target of rapamycin C1 (mTORC1) pathway based on decreases in phospho-p70 S6K and phospho-4E-BP1, 2 substrates of this enzyme. In addition, treatment of these cells with SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2), and the combination of SMI-4a and a mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was highly synergistic in killing pre-T-LBL cells. SMI-4a blocked the rapamycin-sensitive mTORC1 activity by stimulating the phosphorylation and thus activating the mTORC1 negative regulator AMP-dependent protein kinase (AMPK).

  • CAS Number: 327033-36-3
  • MF: C11H6F3NO2S
  • MW: 273.231
  • Catalog: Pim
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Depatuxizumab

Depatuxizumab is a brain-penetrant and humanized tumor-specific anti EGFR monoclonal antibody. Depatuxizumab inhibits the growth of xenograft models of mutant EGFRvIII and wild-type EGFR. Depatuxizumab can be used for research on cancer[1].

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

SYK/JAK-IN-1

SYK/JAK-IN-1 is dual SYK/JAK inhibitor with IC50s of <5 nM for SYK and JAK2, respectively[1].

  • CAS Number: 2737326-28-0
  • MF: C24H26N8O3
  • MW: 474.52
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Broussonin E

Broussonin E is a phenolic compound and shows anti-inflammatory activity. Broussonin E can suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway. Broussonin E can be used for the research of inflammation-related diseases such as atherosclerosis[1].

  • CAS Number: 90902-21-9
  • MF: C17H20O4
  • MW: 288.338
  • Catalog: JAK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 464.9±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 235.0±27.3 °C

AS2863619

AS2863619 enables conversion of antigen-specific effector/memory T cells into Foxp3+ regulatory T (Treg) cells for the treatment of various immunological diseases. AS2863619 is a potent, orally active cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor with IC50s of 0.61 nM and 4.28 nM, respectively. STAT5 activation enhanced by AS2863619 inhibition of CDK8/19, which consequently activates the Foxp3 gene[1].

  • CAS Number: 2241300-51-4
  • MF: C16H14Cl2N8O
  • MW: 405.24
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pan-HER-IN-2

pan-HER-IN-2 (Compound C6) is a reversible, orally active pan-HER inhibitor with IC50 values of 0.72, 2.0, 8.2 and 75.1 nM against EGFR, HER4, EGFRT790M/L858R and HER2, respectively. pan-HER-IN-2 induces apoptosis and shows antitumor activities[1].

  • CAS Number: 1639040-95-1
  • MF: C19H15BrClN5O
  • MW: 444.71
  • Catalog: Apoptosis
  • 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

HER2-IN-7

HER2-IN-7 is a potent inhibitor of HER2. Deregulation of ErbB family signalling modulates proliferation, invasion, metastasis, angiogenesis, and tumour cell survival. HER2-IN-7 has the potential for the research of diseases associated ErbBs (especially HER2), including cancer (extracted from patent WO2019214634A1, compound 23)[1].

  • CAS Number: 2387574-01-6
  • MF: C28H26F3N7O3
  • MW: 565.55
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT3 degrader-1

STAT3 degrader-1 (compound 295) is a potent STAT3 degrader. STAT3 degrader-1 can be used for researching anticancer[1].

  • CAS Number: 2497585-16-5
  • MF: C58H63F5N9O12PS
  • MW: 1236.20
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hjc0149

HJC0149 is a potent orally bioavailable signal transducer and activator of transcription 3 inhibitor.

  • CAS Number: 1430330-65-6
  • MF: C15H10ClNO4S
  • MW: 335.76
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AS1517499

AS1517499 is a potent STAT6 inhibitor with an IC50 of 21 nM.

  • CAS Number: 919486-40-1
  • MF: C20H20ClN5O2
  • MW: 397.85800
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CX-6258 hydrochloride

CX-6258 hydrochloride is a potent and kinase selective pan-Pim kinases inhibitor, with IC50s of 5 nM, 25 nM and 16 nM for Pim-1, Pim-2 and Pim-3, respectively[1].

  • CAS Number: 1353859-00-3
  • MF: C26H25Cl2N3O3
  • MW: 498.401
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

INCB053914 phosphate

INCB053914 phosphate is an inhibitor of Pim extracted from patent WO 2017044730 A1, compound 1; has an IC50 of less than 35 nM.

  • CAS Number: 2088852-47-3
  • MF: C26H29F3N5O7P
  • MW: 611.51
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mutated EGFR-IN-3

Mutated EGFR-IN-3 (compound 3) is a potent, ATP-competitive and highly selective allosteric dibenzodiazepinone inhibitor of the EGFR(L858R/T790M) and EGFR(L858R/T790M/C797S) mutants with IC50 values of 12 nM and 13 nM, respectively[1].

  • CAS Number: 2375107-27-8
  • MF: C31H29FN4O2
  • MW: 508.59
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

α7 nAchR-JAK2-STAT3 agonist 1

α7 nAchR-JAK2-STAT3 agonist 1 is a potent α7 nAchR-JAK2-STAT3 agonist, with an IC50 value of 0.32 μM for nitric oxide (NO). α7 nAchR-JAK2-STAT3 agonist 1 effectively suppresses the expression of iNOS, IL-1β, and IL-6 in murine RAW264.7 macrophages. α7 nAchR-JAK2-STAT3 agonist 1 can inhibit LPS-induced NO release, NF-κB activation and cytokine production. α7 nAchR-JAK2-STAT3 can be used for researching sepsis[1].

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

(E/Z)-AG490

(E/Z)-AG490 ((E/Z)-Tyrphostin AG490) is a racemic compound of (E)-AG490 and (Z)-AG490 isomers. (E)-AG490 (HY-12000) is a tyrosine kinase inhibitor that inhibits EGFR, Stat-3 and JAK2/3.

  • CAS Number: 134036-52-5
  • MF: C17H14N2O3
  • MW: 294.30500
  • Catalog: JAK
  • Density: 1.337g/cm3
  • Boiling Point: 615.2ºC at 760mmHg
  • Melting Point: 215ºC
  • Flash Point: 325.9ºC

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

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