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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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

CEP-1347

CEP-1347 is an inhibitor of the JNK/SAPK pathway with neuroprotective effects.

  • CAS Number: 156177-65-0
  • MF: C33H33N3O5S2
  • MW: 615.76200
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pan-HER-IN-1

pan-HER-IN-1 (Compound C5) is an irreversible, orally active pan-HER inhibitor with IC50 values of 0.38, 1.6, 2.2 and 3.5 nM against EGFR, HER4, EGFRT790M/L858R and HER2, respectively. pan-HER-IN-1 induces apoptosis and shows antitumor activities[1].

  • CAS Number: 1639040-94-0
  • MF: C19H14BrN5O
  • MW: 408.25
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

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

Oritinib

Oritinib (SH-1028), an irreversible third-generation EGFR TKI, overcomes T790M-mediated resistance in non-small cell lung cancer. Oritinib (SH-1028), a mutant-selective inhibitor of EGFR kinase activity, inhibits EGFRWT, EGFRL858R, EGFRL861Q, EGFRL858R/T790M, EGFRd746-750 and EGFRd746-750/T790M kinases, with IC50s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM, respectively[1].

  • CAS Number: 2035089-28-0
  • MF: C31H37N7O2
  • MW: 539.67
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY5

LY5 is a STAT3 inhibitor with an IC50 value of 0.5 μM. LY5 induces Apoptosis and inhibits STAT3 phosphorylation. LY5 shows antitumor activity in vivo, it can be used for the research of cancer[1].

  • CAS Number: 1436382-03-4
  • MF: C15H11N3O4S
  • MW: 329.331
  • Catalog: Apoptosis
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 635.6±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 338.2±34.3 °C

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

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

Povorcitinib phosphate

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

  • CAS Number: 1637677-33-8
  • MF: C23H25F5N7O5P
  • MW: 605.45
  • Catalog: JAK
  • 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

GLPG0634

GLPG0634 is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively.

  • CAS Number: 1206161-97-8
  • MF: C21H23N5O3S
  • MW: 425.504
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • 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

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

Tyrphostin 8

Tyrphostin 8 is a tyrosine kinase, with an IC50 of 560 μM for EGFR kinase. Tyrphostin 8 is also a GTPase inhibitor. Tyrphostin 8 can inhibit the protein serine/threonine phosphatase calcineurin (IC50=21 μM)[1][2][3].

  • CAS Number: 3785-90-8
  • MF: C10H6N2O
  • MW: 170.17
  • Catalog: Ras
  • Density: 1.29 g/cm3
  • Boiling Point: 354.3ºC at 760 mmHg
  • Melting Point: 186-189 °C
  • Flash Point: 168.1ºC

MTP

MTP is a PKM2 inhibitor. MTP induces cancer cell apoptosis by modulating caspase-3 activation. MTP induces autophagy and increases ROS generation. MTP also inhibits JAK2 signaling. MTP can be used for research of oral squamous cell carcinoma[1].

  • CAS Number: 2377372-62-6
  • MF: C29H23F3N4O2
  • MW: 516.51
  • Catalog: Apoptosis
  • 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

O-Desmethyl gefitinib

O-Desmethyl gefitinib is an active metabolite of Gefitinib in human plasma. The formation of O-desmethyl gefitinib is dependent on CYP2D6 activity. O-desmethyl gefitinib inhibits EGFR with an IC50 of 36 nM in subcellular assays[1][2].

  • CAS Number: 847949-49-9
  • MF: C21H22ClFN4O3
  • MW: 432.87600
  • Catalog: EGFR
  • Density: 1.386g/cm3
  • Boiling Point: 606.4ºC at 760 mmHg
  • Melting Point: 117-120ºC
  • Flash Point: 320.5ºC

Laprituximab emtansine

Laprituximab emtansine (IMGN-289) is an immunotoxin targeting HER1. Laprituximab emtansine is an EGFR antibody-drug conjugate (ADC) consisting of the J2898A antibody, DM1 (anti-microtubule agent) and the SMCC thioether linker. Laprituximab emtansine can be used for cancer research[1][2][3].

  • Density: N/A
  • 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

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

TCS PIM-1 1

TCS PIM-1 1(sc-204330) is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s >20,000 nM).IC50 value: 50 nM [1]Target: Pim-1TCS PIM-1 1 bound convincingly within the ATP-binding site of Pim-1 suggesting an ATP-competitive inhibitory mechanism. Preliminary data further suggested that 1 lacked in vitro inhibitory activity toward related serine/threonine kinases Pim-2 and MEK1/2 (IC50 > 20 lM). Hence, small molecules similar to TCS PIM-1 1 may serve as useful starting scaffolds for the development of other improved yet selective Pim-1 inhibitors.

  • CAS Number: 491871-58-0
  • MF: C18H11BrN2O2
  • MW: 367.196
  • Catalog: Pim
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 592.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 312.2±30.1 °C

Yuanhuadin

Yuanhuadin, extracted from Genkwa Flos Daphne genkwa, has antitumor activity through inhibiting Akt/mTOR and EGFR pathways, induce cell-cycle arrest and abortion[1].

  • CAS Number: 76402-66-9
  • MF: C32H42O10
  • MW: 586.67000
  • Catalog: EGFR
  • Density: 1.34g/cm3
  • Boiling Point: 704.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 222.4ºC

Cinrebafusp alfa

Cinrebafusp alfa (PRS 343) is a high affinity CD137/HEr2 bispecfic anticalin-based drug. Cinrebafusp alfa binds to recombinant human HER2 (Kd=0.3 nM) and human monomeric CD137 (4-1BB; Kd=5 nM). Cinrebafusp alfa facilitates T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation, further enhancing T-cell receptor-mediated activity and leading to tumor destruction. Cinrebafusp alfa has the potential for HER2+ solid tumors research[1][2].

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

Lapatinib ditosylate hydrate

Lapatinib ditosylate monohydrate (GW572016 ditosylate monohydrate) is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively[1].

  • CAS Number: 388082-78-8
  • MF: C86H86Cl2F2N8O21S6
  • MW: 943.476
  • Catalog: Autophagy
  • Density: 1.403 g/mL (20.84 °C)
  • Boiling Point: 750.7ºC at 760 mmHg
  • Melting Point: 237 - 239 °C
  • Flash Point: 68 °F