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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YS-363

YS-363 is a potent, selective, and orally active EGFR inhibitor, with IC50s of 0.96 nM and 0.67 nM for wild-type and L858R mutant forms of EGFR, respectively. YS-363 can induce G0/G1 cell cycle arrest and apoptosis[1].

  • CAS Number: 2470908-90-6
  • MF: C30H30N4O3
  • MW: 494.58
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neratinib (HKI-272)

Neratinib is an orally available, irreversible tyrosine kinase inhibitor with IC50s of 59 nM and 92 nM for HER2 and EGFR, respectively.

  • CAS Number: 698387-09-6
  • MF: C30H29ClN6O3
  • MW: 557.043
  • Catalog: EGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 757.0±60.0 °C at 760 mmHg
  • Melting Point: 184 °C
  • Flash Point: 411.6±32.9 °C

PD-161570

PD-161570 is a potent and ATP-competitive human FGF-1 receptor inhibitor with an IC50 of 39.9 nM and a Ki of 42 nM. PD-161570 also inhibits the PDGFR, EGFR and c-Src tyrosine kinases with IC50 values of 310 nM, 240 nM, and 44 nM, respectively. PD-161570 inhibits PDGF-stimulated autophosphorylation and FGF-1 receptor phosphorylation with IC50s of 450 nM and 622 nM, respectively[1][2]. PD-161570 is also a bone morphogenetic proteins (BMPs) and TGF-β signaling inhibitor[3].

  • CAS Number: 192705-80-9
  • MF: C26H35Cl2N7O
  • MW: 532.50800
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 157 °C
  • Flash Point: N/A

PP3

PP 3 (Compound 3) is an EGFR tyrosine kinase inhibitor with an IC50 of 2.7 μM[1].

  • CAS Number: 5334-30-5
  • MF: C11H9N5
  • MW: 211.223
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 364.0±35.0 °C at 760 mmHg
  • Melting Point: 214-217 °C
  • Flash Point: 173.9±25.9 °C

Ubiquinone Q0

Coenzyme Q0 (CoQ0) is a potent, oral active ubiquinone compound can be derived from Antrodia cinnamomea. Coenzyme Q0 induces apoptosis and autophagy, suppresses of HER-2/AKT/mTOR signaling to potentiate the apoptosis and autophagy mechanisms. Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of inflammation and redox imbalance. Coenzyme Q0 has anti-angiogenic activity through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling[1][2][3].

  • CAS Number: 605-94-7
  • MF: C9H10O4
  • MW: 182.173
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 331.4±42.0 °C at 760 mmHg
  • Melting Point: 58-60 °C(lit.)
  • Flash Point: 148.6±27.9 °C

Simotinib hydrochloride

Simotinib hydrochloride is a selective, specific, and orally bioavailable EGFR tyrosine kinase inhibitor, with an IC50 of 19.9 nM. Antineoplastic activities[1].

  • CAS Number: 1538617-88-7
  • MF: C25H27Cl2FN4O4
  • MW: 537.41
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4H-Pyran-4-one,2,6-bis(4-methoxyphenyl)-

NSC81111 is a potent and orally active EGFR-TK inhibitor with an IC50 of 0.15 nM. NSC81111 has anticaner effects[1].

  • CAS Number: 1678-14-4
  • MF: C19H16O4
  • MW: 308.32800
  • Catalog: EGFR
  • Density: 1.218g/cm3
  • Boiling Point: 528.3ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 235.1ºC

WP1066

WP1066 is an inhibitor of JAK2 and STAT3, and also shows effect on STAT5 and ERK1/2, without affecting JAK1 and JAK3.

  • CAS Number: 857064-38-1
  • MF: C17H14BrN3O
  • MW: 356.217
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 569.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 298.5±30.1 °C

8α-Tigloyloxyhirsutinolide 13-O-acetate

8α-Tigloyloxyhirsutinolide 13-O-acetate is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and Pyroptosis, and late DNA damage, cell cycle arrest, Apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo[1][2].

  • CAS Number: 83182-58-5
  • MF: C22H28O8
  • MW: 420.453
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 589.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 201.4±23.6 °C

CHZ868

CHZ868 is a type II JAK2 inhibitor with an IC50 of 0.17 μM in EPOR JAK2 WT Ba/F3 cell.

  • CAS Number: 1895895-38-1
  • MF: C22H19F2N5O2
  • MW: 423.415
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/HER2/CDK9-IN-2

EGFR/HER2/CDK9-IN-2 (Compound 9) is a potent inhibitor of EGFR/HER2/CDK9 with IC50s of 145.35, 129.07, and 117.13 nM, respectively. EGFR/HER2/CDK9-IN-2 exhibits remarkable antitumor activity[1].

  • CAS Number: 1180924-34-8
  • MF: C23H20N4O5S2
  • MW: 496.56
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Khellin

Khellin, a naturally occurring furochromone, is an EGFR inhibitor with an IC50 of 0.15 µM. Khelline has anti-proliferative activity in vitro. Khellin has antispasmodic and coronary vasodilator effects[1][2].

  • CAS Number: 82-02-0
  • MF: C14H12O5
  • MW: 260.242
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 482.1±0.0 °C at 760 mmHg
  • Melting Point: 150-154ºC
  • Flash Point: 218.8±28.7 °C

Ascochlorin

Ascochlorin (Ilicicolin D), an isoprenoid antibiotic, mediates its anti-tumor effects predominantly through the suppression of STAT3 signaling cascade. Ascochlorin induces apoptosis. Anti-inflammatory activity[1][2][3].

  • CAS Number: 26166-39-2
  • MF: C23H29ClO4
  • MW: 404.92700
  • Catalog: Apoptosis
  • Density: 1.199g/cm3
  • Boiling Point: 556.9ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 290.6ºC

Futuximab

Futuximab is a chimeric monoclonal antibody targeting non-overlapping epitopes on EGFR. Futuximab has antineoplastic activity[1].

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

SMI-16a

SMI-16a is a selective Pim kinase inhibitor with IC50 values of 0.15, 0.02 and 48 μM for Pim1, Pim2 and PC3 cells, respectively.

  • CAS Number: 587852-28-6
  • MF: C13H13NO3S
  • MW: 263.312
  • Catalog: Pim
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pimozide

Pimozide is a dopamine receptor antagonist, with Kis of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a Ki of 39 nM; Pimozide also inhibits STAT3 and STAT5.

  • CAS Number: 2062-78-4
  • MF: C28H29F2N3O
  • MW: 461.546
  • Catalog: Adrenergic Receptor
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 649.0±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 346.3±34.3 °C

Ponezumab

Ponezumab (PF-04360365) is a humanised anti-amyloid IgG2 monoclonal antibody. Ponezumab reduces Aβ levels in the central nervous system and improves performance in mice in various models of learning and memory. Ponezumab can be used in study of Alzheimer's disease[1].

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

Trastuzumab

Trastuzumab (PBS) is a humanized IgG1 monoclonal antibody for patients with invasive breast cancers that overexpress HER2. Trastuzumab (PBS) has the potential for HER2 Positive Metastatic Breast Cancer and HER2 Positive Gastric Cancer research.

  • CAS Number: 180288-69-1
  • MF: C6470H10012N1726O2013S42
  • MW: 145531.50
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-46

EGFR-IN-46 is a potent EGFR and FAK dual inhibitor with IC50s of 20.17 nM, 14.25 nM, respectively. EGFR-IN-46 significantly inhibits the growth of cancer cells. EGFR-IN-46 induces cell apoptosis[1].

  • CAS Number: 2764772-88-3
  • MF: C27H32F3N3O3
  • MW: 503.56
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

afatinib

Afatinib (BIBW 2992) is an irreversible EGFR family inhibitor with IC50s of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively.

  • CAS Number: 850140-72-6
  • MF: C24H25ClFN5O3
  • MW: 485.938
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 676.9±55.0 °C at 760 mmHg
  • Melting Point: 100 - 102 °C
  • Flash Point: 363.2±31.5 °C

TAS0728

TAS0728 is a potent, selective, oral active, irreversible and covalent-binding HER2 inhibitor, binds to HER2 at C805, inhibits its kinase activity, with an IC50 of 13 nM. TAS0728 shows IC50s of 4.9, 8.5, 31, 65, 33, 25, 86 and 36 nM for BMX, HER4, BLK, EGFR, JAK3, SLK, LOK and human HER2, respectively. TAS0728 also inhibits the phosphorylation of HER2, HER3, and downstream effectors, shows no obvious effect on EGFR. Antitumor activity[1].

  • CAS Number: 2088323-16-2
  • MF: C26H32N8O3
  • MW: 504.58
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-71

EGFR-IN-71 is a potent narrow spectrum epidermal growth factor receptor (EGFR) inhibitor with IC50 values of 3.7 μM. EGFR-IN-71 can be used for researching chordoma[1].

  • CAS Number: 2676155-98-7
  • MF: C16H9ClIN3
  • MW: 405.62
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Thi-DPPY

Thi-DPPY (compound 8e) is a potent and orally active JAK3 inhibitor with IC50 values of 62.4, 1.38 nM for BTK, JAK, respectively. Thi-DPPY shows anti-proliferative activity against HBE cells. Thi-DPPY shows anti-inflammatory activity in vivo. Thi-DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].

  • CAS Number: 2307699-34-7
  • MF: C28H28ClN5O4S
  • MW: 566.07
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Panitumumab

Panitumumab (ABX-EGF) is a fully human IgG2 anti-EGFR monoclonal antibody. Panitumumab has an anti-tumor activity[1].

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

JAK1/TYK2-IN-1

JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 (IC50 = 29 and 41 nM respectively).

  • CAS Number: 1883300-48-8
  • MF: C18H20F3N7O
  • MW: 407.39
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD1480

AZD-1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of < 0.4 nM, selectively against JAK3 and Tyk2, and to a smaller extent against JAK1.

  • CAS Number: 935666-88-9
  • MF: C14H14ClFN8
  • MW: 348.766
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 575.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 301.7±32.9 °C

LFM-A13

LFM-A13 is a potent BTK, JAK2, PLK inhibitor, inhibits recombinant BTK, Plx1 and PLK3 with IC50s of 2.5 μM, 10 μM and 61 μM. LFM-A13 has antiproliferative activity and anticancer activity. LFM-A13 can be used in cancer-related research[1][3][4]

  • CAS Number: 62004-35-7
  • MF: C11H8Br2N2O2
  • MW: 360.00
  • Catalog: Polo-like Kinase (PLK)
  • Density: 1.9±0.1 g/cm3
  • Boiling Point: 487.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 248.9±28.7 °C

SC-99

A novel selective STAT3 inhibitor that inhibits JAK2-STAT3 activation but has no effects on other transcription factors such as NF-κB, and kinases such as AKT, ERK, and c-Src; inhibits STAT3 phosphorylation, dimerization and nuclear translocation, downregulates STAT3-modulated gene expression and induces MM cell apoptosis; delays tumor growth in MM xenograft models (30mg/kg); orally active.

  • CAS Number: 882290-02-0
  • MF: C15H8Cl2FN3O
  • MW: 336.147
  • Catalog: Apoptosis
  • Density: 1.38±0.1 g/cm3(Predicted)
  • Boiling Point: 459.4±55.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-6

JAK3/BTK-IN-6 (compound 14h) is a potent BTK and JAK3 dual inhibitor, with IC50 values of 0.6 and 0.4 nM, respectively. JAK3/BTK-IN-6 shows good metabolic stability in human liver microsome. JAK3/BTK-IN-6 can be used for hematological and immune diseases research[1].

  • CAS Number: 2243136-03-8
  • MF: C21H17BF3N5O3
  • MW: 455.20
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desmethyl dosimertinib-d5

N-Desmethyl dosimertinib-d5 is the deuterium labeled Dosimertinib (HY-142283). Dosimertinib is a highly potent, selective, and orally active deuterated EGFR inhibiotor. Dosimertinib can be used for the research of non-small-cell lung cancer[1][2].

  • CAS Number: 2719691-00-4
  • MF: C27H26D5N7O2
  • MW: 490.61
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A