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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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

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

SD-1029

SD-1029 (NSC 371488) is a potent inhibitor of Stat3 activation, suppresses EGFP-Stat3 nuclear translocation at 10 uM in both BHK-21 and U2-OS cells; inhibits Stat3-mediated antiapoptotic protein expression (Bcl-XL, MCL-1, and survivin), and suppresses phosphotyrosine levels of JAK2; inhibits IL-6 or oncostatin-induced Stat3 nuclear translocation at micromolar range, enhances apoptosis induced by paclitaxel in human cancer cells.

  • CAS Number: 118372-34-2
  • MF: C25H30Cl2N2O32HBr
  • MW: 639.247
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ACT001

ACT001 is an orally active PAI-1 inhibitor by inhibiting the phosphorylation of PI3K and AKT. ACT001 inhibits the phosphorylation of STAT3 and PD-L1 expression by directly binding to STAT3. ACT001, a fumarate salt form of DMAMCL (a prodrug of Micheliolide), can cross the blood-brain barrier. ACT001 has potent anti-glioblastoma (GBM) activity and immunomodulatory effects[1][2].

  • CAS Number: 1582289-91-5
  • MF: C21H31NO7
  • MW: 409.47
  • 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

AC-4-130

AC-4-130 is a novel, potent STAT5 SH2 domain inhibitor, binds to and efficiently blocks STAT5 activation and subsequent transcriptional activity, shows high selectivity for STAT5 over STAT1 and STAT3; disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription; substantially impairs the proliferation and clonogenic growth of human AML cell lines and primary FLT3-ITD+ AML patient cells in vitro and in vivo; synergistically increases the cytotoxicity of the JAK1/2 inhibitor Ruxolitinib and the p300/pCAF inhibitor Garcinol in vivo.

  • CAS Number: 1834571-82-2
  • MF: C37H36ClF5N2O5S
  • MW: 751.206
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tezatabep matraxetan

Tezatabep matraxetan is a radiolabeled polypeptide used for diagnosis and research of cancer characterized by overexpression of HER2[1].

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

HER2-IN-13

HER2-IN-13 (Compound 33) is an HER2 inhibitor with an IC50 of 8 nM. HER2-IN-13 also inhibits wt-EGFR with an IC50 of 0.40 μM[1].

  • CAS Number: 2414056-34-9
  • MF: C26H23ClF2N8O3
  • MW: 568.96
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

25-Deacetylcucurbitacin A

25-Deacetylcucurbitacin A is a Cucurbitane-Type triterpenoid and has the potential to be an anti-cancer agent and JAK/STAT3 signaling pathway inhibitor[1].

  • 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

EGFR-IN-55

EGFR-IN-55 (Compound 8a) is a potent EGFR inhibitor with IC50 values of 70 nM and 3.9 nM against EGFRWT and EGFRL858R/T790M, respectively. EGFR-IN-55 arrests NCI-H1975 cells in G0/G1 phase and shows anticancer activity[1].

  • CAS Number: 2057423-46-6
  • MF: C25H25Cl2N7O2
  • MW: 526.42
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC31205

Pim-1/2 kinase inhibitor 1 is an orally active pim-1/2 kinase inhibitor. Pim-1/2 kinase inhibitor 1 blocks the ability of Pim kinases to phosphorylate peptides, and inhibits the pim protein kinase directed phosphorylation of 4E-BP1 and p27Kip1. Pim-1/2 kinase inhibitor 1 can be used in study of cancer, especially prostate cancer[1].

  • CAS Number: 6320-51-0
  • MF: C11H9NO3S
  • MW: 235.25900
  • Catalog: Pim
  • Density: 1.391g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Laprituximab

Laprituximab (J2898A) is a humanized IgG1 anti-EGFR antibody that can be used for the synthesis of ADC IMGN289[1].

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

Cirsilineol

Cirsilineol, a natural flavone compound, selectively inhibits IFN-γ/STAT1/T-bet signaling in intestinal CD4+ T cells. Cirsilineol has potent immunosuppressive and anti-tumor properties. Cirsilineol significantly ameliorates trinitro-benzene sulfonic acid (TNBS)-induced T-cell-mediated experimental colitis in mice[1].

  • CAS Number: 41365-32-6
  • MF: C18H16O7
  • MW: 344.31500
  • Catalog: IFNAR
  • Density: 1.387g/cm3
  • Boiling Point: 585ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 215.2ºC

EGFR-IN-88

EGFR-IN-88 (Compound 4i) is an EGFR inhibitor (IC50: 87 nM). EGFR-IN-88 shows cytotoxicity against A549 cell with an IC50? of 3.902? μM. EGFR-IN-88 can induce cell apoptosis[1].

  • CAS Number: 2944452-34-8
  • MF: C22H18Cl2N4O2S
  • MW: 473.37
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Galiellalactone

Galiellalactone is a is a small non-toxic and non-mutagenic fungal metabolite, a selective inhibitor of STAT3 signaling, with an IC50 of 250-500 nM. Galiellalactone can be used to research castration-resistant prostate cancer[1][2][3].

  • CAS Number: 133613-71-5
  • MF: C11H14O3
  • MW: 194.227
  • Catalog: STAT
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 400.7±38.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 182.1±19.5 °C

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

PROTAC EGFR degrader 5

PROTAC EGFR degrader 5 (Compound 10), a PROTAC EGFR degrader, potently degrades EGFRDel19 in HCC827 cells with the DC50 of 34.8 nM. PROTAC EGFR degrader 5 significantly induces the apoptosis of HCC827 cells and arrest the cells in G1 phase[1].

  • CAS Number: 2409793-36-6
  • MF: C57H72FN13O5S
  • MW: 1070.33
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

RET-IN-19

RET-IN-19 (compound 59) is a potent RET inhibitor, with IC50 values of 6.8 and 13.51 nM against RET-wt and RET V804M, respectively. RET-IN-19 shows anticancer activity. RET-IN-19 can be used for non-small cell lung cancer (NSCLC) research[1].

  • CAS Number: 2484919-71-1
  • MF: C28H28N6O4S
  • MW: 544.62
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nezulcitinib

Nezulcitinib (TD-0903) is an inhaled and lung-selective pan-Janus kinase (JAK) inhibitor. Nezulcitinib can be used for the research of COVID-19 associated acute lung injury and impaired oxygenation[1][2].

  • CAS Number: 2412496-23-0
  • MF: C30H37N7O2
  • MW: 527.66
  • 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

JAK1-IN-8

JAK1-IN-8, a potent JAK1 inhibitor (IC50<500 nM), compound 28, extracted from patent WO2016119700A1[1].

  • CAS Number: 1973485-18-5
  • MF: C22H23FN4O3S
  • MW: 442.51
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SD 1008

SD-1008 is a potent JAK inhibitor. SD-1008 inhibits tyrosyl phosphorylation of STAT3, JAK2 and Src. SD-1008 also reduces STAT3-dependent luciferase activity. SD-1008 enhances apoptosis induced by Paclitaxel in ovarian cancer cells via directly blocking the JAK-STAT3 signaling pathway[1].

  • CAS Number: 960201-81-4
  • MF: C18H19NO5
  • MW: 329.35
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC EGFR degrader 8

PROTAC EGFR degrader 8 (T-184) is a PROTAC EGFR degrader. PROTAC EGFR degrader 8 degrades EGFR in HCC827 cell with a DC50 of 15.56 nM. PROTAC EGFR degrader 8 inhibits H1975, PC-9, HCC827 cell growth with IC50s of 7.72 nM, 121.9 nM, 14.21 nM. PROTAC EGFR degrader 8 can be used for research of cancer, especially NSCLC[1].

  • CAS Number: 2925923-46-0
  • MF: C40H46ClN11O5
  • MW: 796.32
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Pimurutamab

Pimurutamab is a humanized IgG1-κ antibody targeting EGFR. Mainly expressed by CHO-K1 cells[1].

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

FD1024

FD1024 is PIM inhibitor (IC50s: 1.96, 38.9, 4.17 nM for PIM1, 2, 3). FD1024 can be used for research of acute myeloid leukemia. FD1024 has strong antiproliferative activity against the tested AML cell lines, with 0.16 μM, 0.12 μM, 1.05 μM, 1.39μM for EOL-1, MV-4-11, KG-1, MOLM-16 cells. FD1024 also has antitumor efficacy in mice[1].

  • CAS Number: 1422456-47-0
  • MF: C21H20F2N4O2S
  • MW: 430.47
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Baricitinib

Baricitinib is a selective and orally bioavailable JAK1 and JAK2 inhibitor with IC50s of 5.9 nM and 5.7 nM, respectively.

  • CAS Number: 1187594-09-7
  • MF: C16H17N7O2S
  • MW: 371.417
  • Catalog: JAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 707.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 381.5±35.7 °C

AST5902

AST5902 is the active metabolite of Firmonertinib (HY-112870) (EGFR inhibitor). AST5902 has antineoplastic activity[1][2].

  • CAS Number: 2412155-74-7
  • MF: C27H29F3N8O2
  • MW: 554.24
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A