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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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

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-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

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

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

Reticuline

Reticuline, isolated from Litsea cubeba, shows anti-inflammatory effects through JAK2/STAT3 and NF-κB signaling pathways. Reticuline inhibits mRNA expressions of TNF-α, and IL-6 and reduces the phosphorylation levels of JAK2 and STAT3[1].

  • CAS Number: 485-19-8
  • MF: C19H23NO4
  • MW: 329.390
  • Catalog: JAK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 504.9±50.0 °C at 760 mmHg
  • Melting Point: 125-126ºC
  • Flash Point: 259.2±30.1 °C

Momelotinib-d8

Momelotinib-d8 (CYT387-d8) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally acitve 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: 1619927-68-2
  • MF: C23H14D8N6O2
  • MW: 422.51
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR Protein Tyrosine Kinase Substrate

EGFR Protein Tyrosine Kinase Substrate is a EGFR protein tyrosine kinase substrate.

  • CAS Number: 945830-38-6
  • MF: C48H73N11O17
  • MW: 1076.16
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Arnicolide D

Arnicolide D is a sesquiterpene lactone isolated from Centipeda minima. Arnicolide D modulates the cell cycle, activates the caspase signaling pathway and inhibits the PI3K/AKT/mTOR and STAT3 signaling pathways. Arnicolide D inhibits Nasopharyngeal carcinoma (NPC) cell viability in a concentration- and time-dependent manner[1].

  • CAS Number: 34532-68-8
  • MF: C19H24O5
  • MW: 332.39100
  • Catalog: Caspase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Homoharringtonine

Homoharringtonine (Omacetaxine mepesuccinate;HHT) is a cytotoxic alkaloid with antitumor properties which acts by inhibiting translation elongation.

  • CAS Number: 26833-87-4
  • MF: C29H39NO9
  • MW: 545.621
  • Catalog: STAT
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 713.1±60.0 °C at 760 mmHg
  • Melting Point: 144-146ºC
  • Flash Point: 385.1±32.9 °C

Itacitinib

Itacitinib is a potent and selective inhibitor of JAK1, with >20-fold selectivity for JAK1 over JAK2 and >100-fold over JAK3 and TYK2; Itacitinib is used in the research of myelofibrosis.

  • CAS Number: 1334298-90-6
  • MF: C26H23F4N9O
  • MW: 553.51400
  • Catalog: JAK
  • Density: 1.57±0.1 g/cm3(Predicted)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momelotinib-3,3,5,5-d6

Momelotinib-3,3,5,5-d6 (CYT387-3,3,5,5-d6) is the deuterium labeled Momelotinib (HY-10961). Momelotinib has inhibitory activity for JAK1/JAK2[1][2].

  • CAS Number: 1619927-67-1
  • MF: C23H16D6N6O2
  • MW: 420.50
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-89

EGFR-IN-89 (compound 13k) is a potent, fourth-generation EGFR mutation inhibitor with an IC50 of 10.1 nM against Del19/T790M/C797S mutations. EGFR-IN-89 shows higher selectivity over wild type[1].

  • CAS Number: 2413029-40-8
  • MF: C26H31FN8O2S
  • MW: 538.64
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tofacitinib (CP-690550)

Tofacitinib is a JAK1/2/3 inhibitor with IC50s of 1, 20, and 112 nM, respectively.

  • CAS Number: 477600-75-2
  • MF: C16H20N6O
  • MW: 312.370
  • Catalog: JAK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 585.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 308.1±30.1 °C

TX-1123

TX-1123 is a potent protein tyrosine kinase (PTK) inhibitor for Src, eEF2-K, and PKA, and EGFR-K/PKC. TX-1123 is a cyclo-oxygenase (COX) inhibitor with IC50 values of 1.16 μM and 15.7 μM for COX2 and COX1, respectively. TX-1123 has low mitochondrial toxicity. TX-1123 can be used in research of cancer[1][2].

  • CAS Number: 157397-06-3
  • MF: C20H24O3
  • MW: 312.40300
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fidasimtamab

Fidasimtamab (IBI-315; BH2950) is a recombinant human IgG1 bispecific antibody that targets, binds and inhibits both HER2 and PD-1 and their downstream signalling pathways, and links PD-1 expressing T cells to HER2 expressing tumour cells. Fidasimtamab has potential immunosuppressive and antitumor activity[1].

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

PIM1-IN-1

PIM1-IN-1 is a potent and highly selective PIM1/3 inhibitor, with IC50s of 7, 5530 and 70 nM for PIM1, PIM2, and PIM3, respectively, inhibits the phosphorylation of BAD, a downstream target of PIM, with an EC50 of 262 nM. PIM1-IN-1 shows no obvious effect on FLT3 or hERG binding. Antiproliferative and anti-cancer activity[1].

  • CAS Number: 1417630-95-5
  • MF: C25H30N8O2
  • MW: 474.56
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mobocertinib(TAK-788)

Mobocertinib is a potent epidermal growth factor receptor (EGFR) inhibitor and an antineoplastic agent, extracted from patent WO2019222093A1, compound A[1][2].

  • CAS Number: 1847461-43-1
  • MF: C32H39N7O4
  • MW: 585.70
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momelotinib-3,3,5,5-d4

Momelotinib-3,3,5,5-d4 (CYT387-3,3,5,5-d4) is the deuterium labeled Momelotinib (HY-10961). Momelotinib has inhibitory activity for JAK1/JAK2[1][2].

  • CAS Number: 1619927-66-0
  • MF: C23H18D4N6O2
  • MW: 418.48
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Elgemtumab

Elgemtumab(LJM716) is a fully human IgG monoclonal antibody. Elgemtumab can specifically bind to HER3, block ligand-dependent and independent HER3 signal transduction and cell proliferation, and has good anti-tumor potential[1].

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

Momelotinib-2,2,6,6-d6

Momelotinib-2,2,6,6-d6 (CYT387-2,2,6,6-d6) is the deuterium labeled Momelotinib (HY-10961). Momelotinib has inhibitory activity for JAK1/JAK2[1][2].

  • CAS Number: 1619927-65-9
  • MF: C23H16D6N6O2
  • MW: 420.50
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

1,2,3,4,5,6-HEXABROMOCYCLOHEXANE

Benzene hexabromide, a bromohydrocarbon, is a potent inhibitor of JAK2 tyrosine kinase autophosphorylation.

  • CAS Number: 1837-91-8
  • MF: C6H6Br6
  • MW: 557.536
  • Catalog: JAK
  • Density: 2.9±0.1 g/cm3
  • Boiling Point: 388.9±42.0 °C at 760 mmHg
  • Melting Point: 82-85°C
  • Flash Point: 183.4±22.6 °C

Rovadicitinib hydrochloride

Rovadicitinib hydrochloride is a JAK inhibitor with an IC50 value <20 nM. Rovadicitinib hydrochloride also exhibits anti-inflammatory activity[1][2].

  • CAS Number: 1948242-60-1
  • MF: C17H20ClN7
  • MW: 357.84
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fraxinellone

Fraxinellone is isolated from the root bark of the Rutaceae plant, Dictamnus dasycarpus. Fraxinellone is a PD-L1 inhibitor and inhibits HIF-1α protein synthesis without affecting HIF-1α protein degradation. Fraxinellone has the potential to be a valuable candidate for cancer treatment by targeting PD-L1[1].

  • CAS Number: 28808-62-0
  • MF: C14H16O3
  • MW: 232.275
  • Catalog: PD-1/PD-L1
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 372.9±30.0 °C at 760 mmHg
  • Melting Point: 116ºC
  • Flash Point: 179.3±24.6 °C

HO-3867

HO-3867 is a selective and potent STAT3 inhibitor and shows good antitumor activity.

  • CAS Number: 1172133-28-6
  • MF: C28H30F2N2O2
  • MW: 464.54700
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pim-1 kinase inhibitor 1

Pim-1 kinase inhibitor 1 is a Pim-1 kinase inhibitor with an IC50 of 0.11 μM for Pim-1 kinase. Pim-1 kinase inhibitor 1 shows anticancer activity to several cancer cell lines by promotes cell apoptosis. Pim-1 kinase inhibitor 1 can be used for the research of cancer[1].

  • CAS Number: 2803505-57-7
  • MF: C19H13N3O3
  • MW: 331.32
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Momelotinib-2,2,6,6-d4

Momelotinib-2,2,6,6-d4 (CYT387-2,2,6,6-d4) is the deuterium labeled Momelotinib (HY-10961). Momelotinib (CYT387) is an orally acitve and ATP-competitive JAK1/JAK2 inhibitor with IC50s of 11 nM and 18 nM, respectively[1][2].

  • CAS Number: 1619927-64-8
  • MF: C23H18D4N6O2
  • MW: 418.48
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A