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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JAK-STAT-IN-1

JAK-STAT-IN-1 (compound 1) is a selective JAK-STAT inhibitor. JAK-STAT-IN-1 can be used for the research of autoimmune disorder[1].

  • CAS Number: 1236666-76-4
  • MF: C21H21N5O2
  • MW: 375.42
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDAC/JAK/BRD4-IN-1

HDAC/JAK/BRD4-IN-1(compound 25ap) is a potent HDAC/JAK/BRD4 triple inhibitor. HDAC/JAK/BRD4-IN-1 inhibit cell growth and induces apoptosis in MDA-MB-231 cells, and shows anticancer activity in vivo[1].

  • CAS Number: 2755325-84-7
  • MF: C24H28N6O3
  • MW: 448.52
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SU 5402

SU 5402 is a potent multi-targeted receptor tyrosine kinase inhibitor with IC50 of 20 nM, 30 nM, and 510 nM for VEGFR2, FGFR1, and PDGFRβ, respectively.

  • CAS Number: 215543-92-3
  • MF: C17H16N2O3
  • MW: 296.320
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 592.6±50.0 °C at 760 mmHg
  • Melting Point: >222ºC (dec.)
  • Flash Point: 312.2±30.1 °C

SB-1317

Zotiraciclib (TG02) is an orally active potent inhibitor of CDK2, JAK2 and FLT3 with IC50 values of 13, 73, and 56 nM, respectively. Zotiraciclib can be used for the research of advanced leukemias and multiple myeloma[1][2].

  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 577.1±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 302.8±32.9 °C

AG 1478 hydrochloride

AG-1478 hydrochloride (Tyrphostin AG-1478 hydrochloride) is a selective EGFR tyrosine kinase inhibitor with IC50 of 3 nM. AG-1478 hydrochloride has antiviral effects against HCV and encephalomyocarditis virus (EMCV)[1][2][3][4].

  • CAS Number: 170449-18-0
  • MF: C16H15Cl2N3O2
  • MW: 352.215
  • Catalog: HCV
  • Density: 1.337g/cm3
  • Boiling Point: 458.5ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 231.1ºC

CK2/PIM1-IN-1

CK2/PIM1-IN-1 is an inhibitor of CK2 and PIM1, with IC50s of 3.787 μM and 4.327 μM for CK2 and PIM1, respectively. CK2/PIM1-IN-1 is developed for the research of proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, vascular disorders, pathogenic infections and certain immunological disorders[1].

  • CAS Number: 292640-28-9
  • MF: C15H9NO4S2
  • MW: 331.37
  • Catalog: Casein Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC PARP/EGFR ligand 1

PROTAC PARP/EGFR ligand 1 is an active compound that can be used for the synthesis of dual PARP EGFR degraders by proteolytic targeting chimera (PROTAC) technology[1].

  • CAS Number: 2661609-57-8
  • MF: C53H56ClF2N9O8
  • MW: 1020.52
  • Catalog: PARP
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JBJ-04-125-02

JBJ-04-125-02 is a potent, mutant-selective, allosteric and orally active EGFR inhibitor with an IC50 of 0.26 nM for EGFRL858R/T790M. JBJ-04-125-02 can inhibit cancer cell proliferation and EGFRL858R/T790M/C797S signaling. JBJ-04-125-02 has anti-tumor activities[1].

  • CAS Number: 2140807-05-0
  • MF: C29H26FN5O3S
  • MW: 543.61
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

15-keto Prostaglandin E2

15-keto-Prostaglandin E2 is an endogenous metabolite. 15-keto-Prostaglandin E2 inhibits STAT3 activation by binding to its Cys259 residue. 15-keto-Prostaglandin E2 can bind and stabilize EP2 and EP4 receptor. 15-keto-Prostaglandin E2 inhibits breast cancer cell growth and progression. 15-keto-Prostaglandin E2 activates PPAR-γ and promotes fungal growth[1][2][3].

  • CAS Number: 26441-05-4
  • MF: C20H30O5
  • MW: 350.45
  • Catalog: PPAR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 534.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 291.1±26.6 °C

Selatinib

Selatinib is a reversible and orally active dual EGFR and ErbB2 inhibitor with IC50s of 13 nM and 22.5 nM, respectively. Selatinib has anticancer effects[1].

  • CAS Number: 1275595-86-2
  • MF: C29H26ClFN4O3S
  • MW: 565.06
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 740.5±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 401.6±32.9 °C

EMI56

EMI56, the derivative of EMI1, displays greater potency toward mutant EGFR than EMI1. EMI56 inhibits EGFR triple mutants[1].

  • CAS Number: 2414374-41-5
  • MF: C21H20N2O3
  • MW: 348.40
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lapatinib-d4-1

Lapatinib-d4-1 is deuterium labeled Lapatinib. Lapatinib (GW572016) 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: 1184264-15-0
  • MF: C29H22D4ClFN4O4S
  • MW: 585.08
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Butyzamide

Butyzamide is an orally active activator of Mpl, a thrombopoietin (TPO) receptor. Butyzamide increases the phosphorylation level of JAK2, STAT3, STAT5 and MAPK. Butyzamide increases the level of human platelets in mouse xenotransplantation assay[1].

  • CAS Number: 1110767-45-7
  • MF: C29H32Cl2N2O5S
  • MW: 591.55
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HS-10296 hydrochloride

HS-10296 hydrochloride is an orally available and third-Generation inhibitor of epidermal growth factor receptor (EGFR)-activating mutations and T790M-resistant mutation with limited activity against wild-type EGFR.

  • CAS Number: 2134096-03-8
  • MF: C30H36ClN7O2
  • MW: 562.11
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-4

JAK3/BTK-IN-4 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-4 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147953A1, compound 003)[1]

  • CAS Number: 2673196-38-6
  • MF: C21H25ClN8O
  • MW: 440.93
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ginsenoside Rk1

Ginsenoside Rk1 is a unique component created by processing the ginseng plant (mainly Sung Ginseng, SG) at high temperatures[1].Ginsenoside Rk1 has anti-inflammatory effect, suppresses the activation of Jak2/Stat3 signaling pathway and NF-κB[2].Ginsenoside Rk1 has anti-tumor effect, antiplatelet aggregation activities, anti-insulin resistance, nephroprotective effect, antimicrobial effect, cognitive function enhancement, lipid accumulation reduction and prevents osteoporosis[1].Ginsenoside Rk1 induces cell apoptosis by triggering intracellular reactive oxygen species (ROS) generation and blocking PI3K/Akt pathway[3].

  • CAS Number: 494753-69-4
  • MF: C42H70O12
  • MW: 766.998
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 854.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 470.6±34.3 °C

EGFR/HER2/CDK9-IN-1

EGFR/HER2/CDK9-IN-1 (Compound 4) is a potent inhibitor of EGFR/HER2/CDK9 with IC50s of 90.17, 131.39, and 67.04 nM, respectively. EGFR/HER2/CDK9-IN-1 exhibits remarkable antitumor activity[1].

  • CAS Number: 879730-44-6
  • MF: C23H21N3O3S2
  • MW: 451.56
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-4

JAK-IN-4 is a prodrug of a JAK inhibitor, effective in murine collagen induced arthritis model[1].

  • CAS Number: 1400877-37-3
  • MF: C18H19N4Na2O6P
  • MW: 464.32
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Egfr-IN-7(TQB3804 )

EGFR-IN-7 (compound 34) is a selective and potent EGFR kinase inhibitor extracted from patent WO2019015655A1, has IC50s of 7.92 nM and 0.218 nM for EGFR (WT) and EGFR (mutant C797S/T790M/L858R) respectively, and shows anti-tumor activity[1].

  • CAS Number: 2267329-76-8
  • MF: C32H41BrN9O2P
  • MW: 694.60
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FGFR2-IN-3 hydrochloride

FGFR2-IN-3 hydrochloride is an orally active selective inhibitor of FGFR2[1].

  • CAS Number: 2688040-45-9
  • MF: C28H25ClFN7O2
  • MW: 546.00
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lepzacitinib

Lepzacitinib is a Janus kinase inhibitor targeting to JAK 1/3. Lepzacitinib exhibits anti-inflammatory effect and inhibits atopic dermatitis and other skin diseases[1].

  • CAS Number: 2321488-47-3
  • MF: C18H21N5O3
  • MW: 355.39
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-8

Tyk2-IN-8 (compound 10) is a selective TYK2 inhibitor, which binds to TYK2 catalytically active JH1 domain with an IC50 of 17 nM, used in the treatment of psoriasis[1].

  • Density: 1.46±0.1 g/cm3(Predicted)
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fosifidancitinib

Fosifidancitinib is a potent and selective inhibitor of JAK kinases 1/3. Fociatinib is used in studies of allergies, asthma and autoimmune diseases[1].

  • CAS Number: 1237168-58-9
  • MF: C21H21FN5O7P
  • MW: 505.39
  • Catalog: JAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 723.1±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 391.1±35.7 °C

H-D-Glu(Trp-OH)-OH

Golotimod (SCV-07), an immunomodulating peptide with antimicrobial activity, significantly increases the efficacy of antituberculosis therapy, stimulates thymic and splenic cell proliferation, and improves macrophage function. Golotimod (SCV-07) inhibits STAT3 signaling and modulates the duration and severity of oral mucositis in animal models that received radiation or a combination of radiation and Cisplatin. Golotimod (SCV-07) is a potential therapeutic for recurrent genital herpes simplex virus type 2 (HSV-2)[1][2][3].

  • CAS Number: 229305-39-9
  • MF: C16H19N3O5
  • MW: 333.33900
  • Catalog: Bacterial
  • Density: 1.428g/cm3
  • Boiling Point: 737.3ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 399.7ºC

JAK3-IN-9

JAK3-IN-9 is an orally active JAK3 inhibitor with IC50 value of 1.7 nM. JAK3-IN-9 is highly selective to the JAK3 signal path. JAK3-IN-9 is lowly toxic with high oral bioavailability, shows good anti-arthritis activity. JAK3-IN-9 can be used in autoimmune disease research[1].

  • CAS Number: 1430095-30-9
  • MF: C17H23N5O4S
  • MW: 393.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyk2-IN-9

Tyk2-IN-9 is a potent,selective and specific inhibitor of JAK kinases, inhibits Tyk2, JAK1 and JAK2 with IC50 values of 6 nM, 21nM and 6nM, respectively. Tyk2-IN-9, example 19, is extracted from patent US2017240552A1[1].

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

Cryptotanshinone

Cryptotanshinone is a natural compound extracted from the root of Salvia miltiorrhiza Bunge that shows antitumor activities. Cryptotanshinone inhibits STAT3 with an IC50 of 4.6 μM.

  • CAS Number: 35825-57-1
  • MF: C19H20O3
  • MW: 296.360
  • Catalog: Autophagy
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 459.0±45.0 °C at 760 mmHg
  • Melting Point: 184-185ºC
  • Flash Point: 203.4±28.8 °C

PIM1-IN-6

PIM1-IN-6 (compound 5h) is a potent PIM-1 inhibitor, with an IC50 of 0.60 μM. PIM1-IN-6 shows the high cytotoxicity activity against HCT-116 and MCF-7 cells, with IC50 values of 1.51 and 15.2 μM, respectively[1].

  • CAS Number: 2439168-69-9
  • MF: C21H18N6O4
  • MW: 418.41
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GDC-046

GDC-046 is a potent, selective, and orally bioavailable TYK2 inhibitor with Kis of 4.8, 0.7, 0.7, and 0.4 nM for TYK2, JAK1, JAK2, and JAK3, respectively[1].

  • CAS Number: 1258292-64-6
  • MF: C16H13Cl2N3O2
  • MW: 350.199
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 518.0±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.1±30.1 °C

AG-1557

AG-1557, compound 22 (T), is a ATP competitive inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase with a pIC50 value of 8.194[1].

  • CAS Number: 189290-58-2
  • MF: C16H14IN3O2
  • MW: 407.206
  • Catalog: EGFR
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 492.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 251.9±28.7 °C