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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PIM-IN-1

PIM-IN-1 is a pan-PIM kinase inhibitor (KG-1, EC50 = 61 nM; pS6, EC50 = 71 nM).

  • CAS Number: 2698319-19-4
  • MF: C15H18ClFN4O
  • MW: 324.78
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-20

JAK-IN-20 is a potent, pan and orally active JAK inhibitor with an IC50s of 7 nM, 5 nM, 14 nM for JAK1, JAK2, JAK3, respectively. JAK-IN-20 shows excellent pharmacokinetics and displays anti-inflammatory efficacy in vivo[1].

  • CAS Number: 1654776-91-6
  • MF: C28H30FN7O2
  • MW: 515.58
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cetuximab sarotalocan

Cetuximab sarotalocan (Cetuximab-IRDye-700DX) is an IRdye700DX (near-infrared photosensitizing dye) conjugate of Cetuximab (anti-EGFR monoclonal antibody). Cetuximab sarotalocan can be used for head and neck cancers research[1][2].

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

JAK-IN-31

JAK-IN-31 (Example 75) is a JAK inhibitor with IC50 ranges of ≤0.01µM, ≤0.01µM, 0.01-0.1 µM and ≤0.01µM for JAK1, JAK2, JAK3 and Tyk2 respectively. JAK-IN-31 can be used in cancer research[1].

  • CAS Number: 2597016-88-9
  • MF: C21H19N7O2S2
  • MW: 465.55
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lavendustin C

Lavendustin C is a potent Ca2+ calmodulin-dependent kinase II (CaMK II) inhibitor with an IC50 of 0.2 µM. Lavendustin C inhibits EGFR-associated tyrosine kinase (IC50=0.012 µM) and pp60c-src(+) kinase (IC50=0.5 µM) [1][2].

  • CAS Number: 125697-93-0
  • MF: C14H13NO5
  • MW: 275.257
  • Catalog: EGFR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 597.5±50.0 °C at 760 mmHg
  • Melting Point: 193-195ºC dec.
  • Flash Point: 315.2±30.1 °C

JAK-IN-34

JAK-IN-34 (compound 11n) is a potent against of JAKs with IC50 values of 0.40, 0.83, 2.10, 1.95 nM target JAK1, JAK2, JAK3, TYK2, respectively. JAK-IN-34 reduces joint swelling with good safety[1].

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

PD 174265

PD 174265 is a potent, cell-permeable, reversible, and selective inhibitor of EGFR with an IC50 of 450 pM[1].

  • CAS Number: 216163-53-0
  • MF: C17H15BrN4O
  • MW: 371.23100
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3 covalent inhibitor-1

JAK3 covalent inhibitor-1 is a potent and selective janus kinase 3 (JAK3) covalent inhibitor with an IC50 of 11 nM and shows 246-fold selectivity vs other JAKs[1].

  • CAS Number: 2300106-50-5
  • MF: C22H17FN6O2S
  • MW: 448.47
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Sacibertinib

Sacibertinib is a tyrosine kinase (Trk) inhibitor with EC50 value of 110 nM and 244 nM for EGFR-TK phosphorylation and HER2, respectively. Antineoplastic activity[1].

  • CAS Number: 1351941-69-9
  • MF: C32H31ClN6O4
  • MW: 599.08
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ML115

ML115 is a molecular probe of the signal transducer and activator of transcription (STAT3). ML115 is a STAT3 agonist[1].

  • CAS Number: 912798-42-6
  • MF: C15H15ClN2O4
  • MW: 322.74
  • Catalog: STAT
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 422.9±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 209.6±28.7 °C

STAT3-IN-17

STAT3-IN-17 is a moderate STAT3 inhibitor (IC50=0.7 μM; HEK-Blue IL-6), with antiproliferative activity in HeLa cells. STAT3-IN-17 has good pharmacokinetic characteristics. STAT3-IN-17 also inhibits pyruvate-ferredoxin oxidoreductase (PFOR), and inhibits Helicobacter pylori[1][2].

  • CAS Number: 1245814-52-1
  • MF: C11H6F3N3O3S
  • MW: 317.24
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

S3I-201

NSC 74859 is a selective Stat3 inhibitor with an IC50 of 86±33 μM.

  • CAS Number: 501919-59-1
  • MF: C16H15NO7S
  • MW: 365.358
  • Catalog: STAT
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 654.7±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 349.8±31.5 °C

Artesunate

Artesunate is an inhibitor of both STAT-3 and exported protein 1 (EXP1).

  • CAS Number: 88495-63-0
  • MF: C19H28O8
  • MW: 384.421
  • Catalog: STAT
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 507.1±50.0 °C at 760 mmHg
  • Melting Point: 132-135ºC
  • Flash Point: 175.6±23.6 °C

Upadacitinib

Upadacitinib (ABT-494) is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM, being developed for the treatment of several autoimmune disorders.

  • CAS Number: 1310726-60-3
  • MF: C17H19F3N6O
  • MW: 380.368
  • Catalog: JAK
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Coprelotamab

Coprelotamab (GB-221) is an IgG-κ monoclonal antibody targeting EGFR2. The commonly used expression system for Coprelotamab is CHO DG44 (Chinese Hamster Ovary) cells[1].

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

Angoline hydrochloride

Angoline hydrochloride is a potent and selective IL6/STAT3 signaling pathway inhibitor with an IC50 of 11.56 μM. Angoline hydrochloride inhibits STAT3 phosphorylation and its target gene expression, and inhibits cancer cell proliferation[1].

  • CAS Number: 1071676-04-4
  • MF: C22H22ClNO5
  • MW: 415.87
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lazertinib

Lazertinib is a potent, highly mutant-selective, blood-brain barrier permeable, orally available and irreversible third-generation EGFR tyrosine kinase inhibitor, and can be used in the research of non-small cell lung cancer.

  • CAS Number: 1903008-80-9
  • MF: C30H34N8O3
  • MW: 554.643
  • Catalog: EGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4-(3-bromoanilino)-6,7-diethoxyquinazoline

EGFR-IN-80 (compound 30) is an EGFR inhibitor with a pIC50 of 10.6[1].

  • CAS Number: 171745-13-4
  • MF: C18H18BrN3O2
  • MW: 388.26
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 492.6±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 251.7±28.7 °C

EGFR/ErbB-2/ErbB-4 inhibitor-2

EGFR/ErbB-2/ErbB-4 inhibitor-2 (Compound 5) is a EGFR and ErbB inhibitor with IC50s of 0.017 μM, 0.08 μM, 1.91 μM[1].

  • CAS Number: 179248-61-4
  • MF: C23H21N3O3
  • MW: 387.43100
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lapatinib (4-Methylbenzenesulfonate)

Lapatinib (GW572016) tosylate is a potent, orally active 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: 1187538-35-7
  • MF: C36H34ClFN4O7S2
  • MW: 753.259
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-63

EGFR-IN-63 is an EGFR inhibition (IC50: 0.096 μM) and it has anticancer activity in MCF-7 cells (IC50: 2.49 μM).

  • CAS Number: 2414635-72-4
  • MF: C20H12BrN5S
  • MW: 434.31
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-59

EGFR-IN-59 (Compound 8c) is a EGFR inhibitor (IC50=190 nM) and apoptosis inducer. EGFR-IN-59 exhibits cytotoxicity against non-small lung cancer cell lines (A549) and normal lung fibroblasts (WI38) with IC50s of 8.62 and 52.6 µM, respectively. EGFR-IN-59 can be used for the research of various cancers such as non-small cell lung cancer (NSCLC), head and neck cancer, breast cancer and colorectal cancer[1].

  • CAS Number: 2529891-44-7
  • MF: C27H23N5O4S
  • MW: 513.57
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ABBV-712

ABBV-712 is a selective inhibitor of Tyrosine kinase 2 (TYK2), with IC50 of 0.195 μM, that play important role in autoimmune diseases[1].

  • CAS Number: 2368945-27-9
  • MF: C24H28N4O5
  • MW: 452.50
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Hispidulin

Hispidulin is a natural flavone with a broad spectrum of biological activities. Hispidulin is a Pim-1 inhibitor with an IC50 of 2.71 μM.

  • CAS Number: 1447-88-7
  • MF: C16H12O6
  • MW: 300.263
  • Catalog: Pim
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 601.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 230.1±25.0 °C

AG 1406

AG 1406 (compound M19) is a HER2 inhibitor, with an IC50 of 10.57 μM for HER2 in BT474 cell and >50 μM for EGFR in EGF-3T3 cell[1].

  • CAS Number: 71308-34-4
  • MF: C16H18N2O
  • MW: 254.32700
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-1 hydrochloride

EGFR-IN-1 hydrochloride is an orally active and irreversible L858R/T790M mutant selective EGFR inhibitor. EGFR-IN-1 hydrochloride potently inhibits Gefitinib-resistant EGFR L858R, T790M with 100-fold selectivity over wild-type EGFR. EGFR-IN-1 hydrochloride displays strong antiproliferative activity against the H1975 cells and the first line mutant HCC827 cells. Antitumor activity[1].

  • CAS Number: 2227455-78-7
  • MF: C28H31ClN6O4
  • MW: 551.04
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT3-IN-13

STAT3-IN-13 (compound 6f) is a potent STAT3 inhibitor. STAT3-IN-13 has anti-proliferative effects and binds to the STAT3 SH2 domain with a KD of 0.46 μM. STAT3-IN-13 inhibits the phosphorylation of STAT3 Y705 and downstream target gene expression. STAT3-IN-13 induces apoptosis in vitro and suppresses the growth and metastasis of tumor in vivo. STAT3-IN-13 can be used for cancer research[1].

  • CAS Number: 2248552-86-3
  • MF: C21H20N6O3S
  • MW: 436.49
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Zanidatamab

Zanidatamab (ZW25) is a humanised, bispecific monoclonal antibody targeting 2 distinct HER2 epitopes (ECD2 and ECD4). Zanidatamab has anti-tumour activity[1].

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

Pumecitinib

Pumecitinib is a Janus kinase (JAK) inhibitor with anti-inflammatory activity[1].

  • CAS Number: 2401057-12-1
  • MF: C17H20N8O2S
  • MW: 400.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

7-epi-Isogarcinol

7-epi-Isogarcinol is a polycyclic polyprenylated acylphloroglucinol (PPAP), with moderate antiproliferative activity. 7-epi-Isogarcinol blocks STAT3 signaling pathway, to induce apoptosis and inhibit cell migration[1].

  • CAS Number: 1141378-40-6
  • MF: C38H50O6
  • MW: 602.80
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A