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.


Anti-infection >
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BI-1622

BI-1622 is an orally active, potent and highly selective HER2 (ERBB2) inhibitor, with an IC50 of 7 nM. BI-1622 shows greater than 25-fold selectivity over EGFR. BI-1622 shows high antitumor efficacy in vivo in xenograft mouse tumor models with engineered H2170 and PC9 cells and had a favorable drug metabolism and pharmacokinetics profile[1].

  • CAS Number: 2681392-19-6
  • MF: C26H24N10O2
  • MW: 508.53
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK1-IN-4

JAK1-IN-4 is a potent and selective JAK1 inhibitor, with IC50s of 85 nM, 12.8 μM and >30 μM for JAK1, JAK2, and JAK3, respectively. JAK1-IN-4 inhibits STAT3 phosphorylation in NCI-H 1975 cells (IC50, 227 nM)[1].

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

Momelotinib-d2

Momelotinib-d2 (CYT387-d2) 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: 1619927-63-7
  • MF: C23H20D2N6O2
  • MW: 416.47
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-1

JAK-IN-1 is a JAK1/2/3 inhibitor with IC50s of 0.26, 0.8 and 3.2 nM, respectively. JAK-IN-1 shows improved selectivity for JAK3 over JAK1.

  • CAS Number: 1334673-53-8
  • MF: C20H24N6O2
  • MW: 380.44
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Filgotinib maleate

Filgotinib (maleate) is a selective and orally active JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM and 116 nM for JAK1, JAK2, JAK3 and TYK2, respectively. Filgotinib (maleate) can be used for rheumatoid arthritis (RA) and Crohn's disease research[1][2].

  • CAS Number: 1802998-75-9
  • MF: C25H27N5O7S
  • MW: 541.58
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DPP

DPP is a Platinum(IV) complex, bearing pterostilbene-derived axial ligand. DPP inhibit the JAK2-STAT3 pathway in breast cancer (BC) cells with antiproliferative activity, and activates caspase-3 and cleaved poly ADP-ribose polymerase to induces apoptosis. DPP promotes the maturation and antigen presentation of dendritic cells, and exhibits in vivo safety[1].

  • CAS Number: 2668267-47-6
  • MF: C36H40Cl2N2O10Pt
  • MW: 926.70
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Oclacitinib

Oclacitinib is a novel JAK inhibitor. Oclacitinib is most potent at inhibiting JAK1 (IC50=10 nM).

  • CAS Number: 1208319-26-9
  • MF: C15H23N5O2S
  • MW: 337.440
  • Catalog: JAK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Trastuzumab deruxtecan

Trastuzumab deruxtecan (DS-8201a) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC). Trastuzumab deruxtecan is composed of a humanized anti-HER2 antibody, an enzymatically cleavable peptide-linker, and a topoisomerase I inhibitor. Trastuzumab deruxtecan can be used for the research of HER2-positive breast cancer and gastric cancer[1][2].

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

Pim-1 kinase inhibitor 5

Pim-1 kinase inhibitor 5 (Compound 4c) is a Pim-1 kinase inhibitor (IC50: 0.61 μM). Pim-1 kinase inhibitor 5 shows cytotoxicity against cancer cells, with IC50s of 6.95-20.19 μM for HepG2, MCF-7, PC3, and HCT-116 cells[1].

  • CAS Number: 2928606-67-9
  • MF: C22H13Cl2N3O
  • MW: 406.26
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HKI 357

HKI-357 is an irreversible dual inhibitor of EGFR and ERBB2 with IC50s of 34 nM and 33 nM, respectively. HKI-357 suppresses EGFR autophosphorylation (at Y1068), and AKT and MAPK phosphorylation[1].

  • CAS Number: 848133-17-5
  • MF: C31H29ClFN5O3
  • MW: 574.04500
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR kinase inhibitor 1

EGFR kinase inhibitor 1 is a potent EGFR inhibitor with IC50s of 37, 1.7, >300 nM for WT, l885R/T790M, L858R/T790M/C797S, respectively. EGFR kinase inhibitor 1 induces apoptosis and cell cycle arrest at G0/G1-phase. EGFR kinase inhibitor 1 inhibits the cell motility. EGFR kinase inhibitor 1 shows antiproliferative and anti-tumor activity[1].

  • CAS Number: 2413958-04-8
  • MF: C30H31N7O2
  • MW: 521.61
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Garcinone C

Garcinone C, a xanthone derivative, is a natural compound extracted from Garcinia oblongifolia Champ that is used as an anti-inflammatory, analgesia, astringency and granulation-promoting medicine, and has potential cytotoxic effects on certain cancers. Garcinone C stimulates the expression levels of ATR and 4E-BP1, while efficiently inhibiting the expression levels of cyclin B1, cyclin D1, cyclin E2, cdc2, Stat3 and CDK7. Garcinone C significantly inhibits cell viability of the human Nasopharyngeal carcinoma (NPC) cell lines CNE1, CNE2, HK1 and HONE1 in a time‑ and dose‑dependent manner[1].

  • CAS Number: 76996-27-5
  • MF: C23H26O7
  • MW: 414.448
  • Catalog: ATM/ATR
  • Density: 1.367
  • Boiling Point: 689.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 239.7±25.0 °C

JAK kinase-IN-1

JAK kinase-IN-1 (Example 1) is a JAK inhibitor. JAK kinase-IN-1 inhibits TYK2, JAK1, JAK2 and JAK3 with IC50 values of 4.2 nM, 32 nM, 27 nM, 3473 nM respectively[1].

  • CAS Number: 2698389-43-2
  • MF: C17H19F2N7OS
  • MW: 407.44
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-3

JAK3/BTK-IN-3 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-3 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147952A1, compound 009)[1]

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

LRRK2-IN-8

LRRK2-IN-8 is a LRRK2 inhibitor. LRRK2-IN-8 inhibits LRRK2 (wt) and LRRK2 (G2019) with IC50s lower than 10 nM, and inhibits TYK2 and NUAK1 with IC50s of 10-100 nM[1].

  • CAS Number: 2770269-44-6
  • MF: C16H12F2N6
  • MW: 326.30
  • Catalog: LRRK2
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

cerdulatinib

Cerdulatinib (PRT062070) is a dual JAK and SYK inhibitor with IC50s of 12, 6, 8 and 32 for JAK1, 2, 3 and SYK, respectively.

  • CAS Number: 1198300-79-6
  • MF: C20H27N7O3S
  • MW: 445.539
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 741.9±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 402.5±35.7 °C

Tomuzotuximab

Tomuzotuximab (Anti-Human EGFR Recombinant Antibody) is a fully human glycoengineered IgG1 monoclonal antibody against EGFR. Tomuzotuximab has anticancer effects[1].

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

PF-06700841

PF-06700841 is a dual JAK1 and TYK2 inhibitor with IC50s of 17 and 23 nM, respectively. Anti-inflammatory activity[1].

  • CAS Number: 1883299-62-4
  • MF: C18H21F2N7O
  • MW: 389.40
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FLLL32

FLLL32 is a STAT3 inhibitor derived from the natural product curcumin. FLLL32 retains the cellular response to cytokines with anti-tumor activity[1].

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

SGI-1776 free base

SGI-1776 is an inhibitor of Pim kinases, with IC50s of 7 nM, 363 nM, and 69 nM for Pim-1, -2 and -3, respectively.

  • CAS Number: 1025065-69-3
  • MF: C20H22F3N5O
  • MW: 405.417
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pim-1 kinase inhibitor 6

Pim-1 kinase inhibitor 6 (Compound 4d) is a potent Pim-1 kinase inhibitor with IC50 value of 0.46 μM, and has significant cytotoxic effect on cancer cells[1].

  • CAS Number: 2928606-69-1
  • MF: C21H10BrCl2N3
  • MW: 455.13
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK/HDAC-IN-1

JAK/HDAC-IN-1 is a potent JAK2/HDAC dual inhibitor, exhibits antiproliferative and proapoptotic activities in several hematological cell lines. JAK/HDAC-IN-1 shows IC50s of 4 and 2 nM for JAK2 and HDAC, respectively[1].

  • CAS Number: 2284621-75-4
  • MF: C19H21Cl2N7O2
  • MW: 450.32
  • Catalog: HDAC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PM-81I

PM-81I is a potent STAT6 inhibitor (targeting the SH2 structural domain) that effectively reduces STAT6 phosphorylation levels. PM-81I can be used in studies of allergic lung disease, allergic rhinitis, chronic obstructive pulmonary disease or cancer[1].

  • CAS Number: 1637532-83-2
  • MF: C43H58F2N3O10P
  • MW: 845.91
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Derazantinib dihydrochloride

Derazantinib (ARQ-087) dihydrochloride is an ATP competitive and orally activeFGFR inhibitor (IC50s: 1.8 nM for FGFR2, 4.5 nM for FGFR1 and 3). Derazantinib dihydrochloride inhibits FGFR phosphorylation. Derazantinib dihydrochloride inhibits tumor growth in multiple xenograft models[1][2].

  • CAS Number: 1821329-75-2
  • MF: C29H31Cl2FN4O
  • MW: 541.487
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Imgatuzumab

Imgatuzumab (RG 7160) is a humanized monoclonal antibody against the EGFR. Imgatuzumab acts as an immunomodulator. Imgatuzumab can be used in research of cancer[1].

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

Unecritinib

Unecritinib (TQ-B3101) is a potent EGFR tyrosine kinase inhibitor. Unecritinib shows anticancer activity. Unecritinib inhibits ALK, ROS1, and MET. Unecritinib has the potential for the research of solid tumor and relapsed or refractory ALK-positive anaplastic large cell lymphoma[1][2].

  • CAS Number: 1418026-92-2
  • MF: C23H24Cl2FN5O2
  • MW: 492.37
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-50

EGFR-IN-50 (Compound 9h) is a potent EGFR inhibitor against L858R resistance mutation (TEL-EGFR-L858R-BaF3: GI50=8 nM, TEL-EGFR-T790M-L858R-BaF3: GI50=6.03 μM). EGFR-IN-50 shows anti-proliferative activity to cancer cells[1].

  • CAS Number: 2044508-48-5
  • MF: C24H26BrN3O4S2
  • MW: 564.51
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Larotinib mesylate hydrate

Larotinib mesylate hydrate is a potent broad-spectrum and orally active tyrosine kinase inhibitor (TKI) with EGFR as the main target with an IC50 of 0.6 nM[1].

  • CAS Number: 2097129-93-4
  • MF: C26H36ClFN4O11S2
  • MW: 699.17
  • Catalog: IRAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Salviolone

Salviolone is a natural diterpenoid derivative that can against melanoma cells. Salviolone exhibits a pleiotropic effect against melanoma by hampering cell cycle progression, STAT3 signaling, and malignant phenotype of A375 melanoma cells[1].

  • CAS Number: 119400-86-1
  • MF: C18H20O2
  • MW: 268.35000
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(2E)-3-(2-hydroxyphenyl)prop-2-enal

2-Hydroxycinnamaldehyde is a phenylpropanoid that can be isolated from the bark of Cinnamomum cassia. 2-Hydroxycinnamaldehyde inhibits Wnt/β-catenin, STAT3 signaling. 2-Hydroxycinnamaldehyde induces cell apoptosis 2-Hydroxycinnamaldehyde has antitumor and anti-inflammation activities[1][2][3].

  • CAS Number: 3541-42-2
  • MF: C9H8O2
  • MW: 148.16
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 311.3±17.0 °C at 760 mmHg
  • Melting Point: 126ºC
  • Flash Point: 131.8±13.5 °C