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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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

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

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

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

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

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

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

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

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

EGFR/ErbB-2 inhibitor-1

EGFR/ErbB-2 inhibitor-1 is a ErbB2/HER2 inhibitor[1].

  • CAS Number: 1135150-79-6
  • MF: C23H15ClFN3OS2
  • MW: 467.97
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Epertinib hydrochloride

Epertinib hydrochloride is a potent, orally active, reversible, and selective tyrosine kinase inhibitor of EGFR, HER2 and HER4, with IC50s of 1.48 nM, 7.15 nM and 2.49 nM, respectively. Epertinib shows potent antitumor activity[1].

  • CAS Number: 2071195-74-7
  • MF: C30H28Cl2FN5O3
  • MW: 596.48
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

5-[4-(1,1-dioxothiomorpholin-4-ylmethyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine

GS-829845 is a major, active metabolite of Filgotinib (HY-18300). GS-829845 is a JAK1 preferential inhibitor but is approximately 10-fold less potent than the parent and with a longer half-life[1][2].

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

AZD-9291 Mesylate

Osimertinib mesylate (AZD-9291 mesylate) is an irreversible and mutant selective EGFR inhibitor with IC50s of 12 and 1 nM against EGFRL858R and EGFRL858R/T790M, respectively.

  • CAS Number: 1421373-66-1
  • MF: C29H37N7O5S
  • MW: 595.713
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TG-46

JAK-IN-35 (compound TG46) is a JAK2 inhibitor that canb be used in cancer research[1].

  • CAS Number: 936091-15-5
  • MF: C26H34N6O3S
  • MW: 510.652
  • Catalog: JAK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 687.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 369.6±34.3 °C

Akt Inhibitor X

10-DEBC is a selective Akt inhibitor. 10-DEBC shows strong inhibitory activity against Moloney murine leukemia virus (Pim) kinase-1 (IC50=1.28 μM)[1].

  • CAS Number: 201788-90-1
  • MF: C20H26Cl2N2O
  • MW: 381.33900
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: 490.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 250.7ºC

QL-1200186

QL-1200186 is anorally activeand selective inhibitor ofTYK2. Oral administration of QL-1200186, dose-dependently inhibitsinterferon-γ(IFNγ) production afterinterleukin-12(IL-12) challenge and significantly ameliorates skin lesions in psoriatic mice[1].

  • CAS Number: 2848664-42-4
  • MF: C26H27N7O3
  • MW: 485.54
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Osimertinib (AZD9291)

Osimertinib (AZD-9291) is an irreversible and mutant selective EGFR inhibitor with IC50s of 12 and 1 nM against EGFRL858R and EGFRL858R/T790M, respectively.

  • CAS Number: 1421373-65-0
  • MF: C28H33N7O2
  • MW: 499.607
  • Catalog: EGFR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

vanicoside B

Vanicoside B is a phenylpropanoyl sucrose derivative, can be isolated from the herb Persicaria dissitiflora. Vanicoside B targets cyclin-dependent kinase 8 (CDK8) and exhibits anti-tumor activity. The potential mechanism is Vanicoside B blocks CDK8-mediated signaling pathways and decreases the expression of epithelial-mesenchymal transition proteins, so that it leads to cell cycle arrest and apoptosis[1][2].

  • CAS Number: 155179-21-8
  • MF: C49H48O20
  • MW: 956.893
  • Catalog: CDK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 1165.0±65.0 °C at 760 mmHg
  • Melting Point: 157-159 °C
  • Flash Point: 339.6±27.8 °C

RO495

RO495 is a potent inhibitor of non-receptor tyrosine-protein kinase 2 (TYK2 kinase)[1].

  • CAS Number: 1258296-60-4
  • MF: C17H14Cl2N6O
  • MW: 389.24
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

OSM-SMI-10B

OSM-SMI-10B a derivative of OSM-SMI-10. OSM-SMI-10B significantly reduces OSM-induced STAT3 phosphorylation in cancer cells upon co-incubation with OSM (Oncostatin M)[1].

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

lavendustin A

Lavendustin A (RG-14355), isolated from Streptomyces Griseolavendus, is a potent, specific and ATP-competitive inhibitor of tyrosine kinase, with an IC50 of 11 ng/mL for EGFR-associated tyrosine kinase[1]. It suppresses VEGF-induced angiogenesis and blocks the induction of LTPGABA-A[2][3].

  • CAS Number: 125697-92-9
  • MF: C21H19NO6
  • MW: 381.37900
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: 741.7ºC at 760 mmHg
  • Melting Point: 205-215 °C
  • Flash Point: 402.4ºC

CX-6258

CX-6258 is a potent, orally efficacious Pim 1/2/3 kinase(IC50=5 nM/25 nM/16 nM) inhibitor with excellent biochemical potency and kinase selectivity.IC50 Value: 5 nM/25 nM/16 nM (Pim 1/2/3) [1]Target: pan-Pimin vitro: CX-6258 inhibited Flt-3 and Pim-3 (IC50=0.134 and 0.016 uM). At 0.5 uM of CX-6258, only Pim-1, Pim-2, Pim-3, and Flt-3 of the 107 kinases tested were inhibited by more than 80%, showing excellent selectivity. CX-6258 was also shown to be a reversible inhibitor of Pim-1 (Ki=0.005 uM). CX-6258 showed robust antiproliferative potencies against all cell lines tested derived from human solid tumors and hematological malignancies. In mechanistic cellular assays with MV-4-11 human AML cells, (13) caused dose-dependent inhibition of the phosphorylation of 2 pro-survival proteins, Bad and 4E-BP1, at the Pim kinase specific sites S112 and S65 and T37/46, respectively[1]. Pim-1 inhibition using the small molecule inhibitor CX-6258 (12 mM, 3 h) diminishes endogenous NKX3.1 steady state levels in 22RV1 and LNCaP cells. CX-6258 treatment (12 mM, 3 h) treatment diminished steady-state levels of ectopic NKX3.1 in PC3 cells. CX-6258 treatment resulted in a significant reduction in NKX3.1 half-life. While ectopically expressed NKX3.1 in control cells had a half-life of _90 min, Pim-1 inhibition reduced the half-life to _52 min [2].in vivo: CX-6258 showed dose-dependent efficacy in mice bearing MV-4-11 xenografts, with 45% and 75% TGI at 50 and 100 mg/kg/day, respectively. Treatment of mice bearing PC3 xenografts with CX-6258 p.o. 50 mg/kg was also well tolerated and produced 51% TGI.

  • CAS Number: 1202916-90-2
  • MF: C26H24ClN3O3
  • MW: 461.940
  • Catalog: Pim
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 697.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 375.8±31.5 °C

STAT5-IN-2

STAT5-IN-2 is a STAT5 inhibitor with EC50s of 9 μM and 5 μM in K562 and KU812 cells, respectively. Potent antileukemic effect[1].

  • CAS Number: 2111834-61-6
  • MF: C26H27N3O
  • MW: 397.51
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A