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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AG-825

AG-825 (Tyrphostin AG-825) is a selective and ATP-competitive ErbB2 inhibitor which suppresses tyrosine phosphorylation, with an IC50 of 0.35 μM. AG-825 displays anti-cancer activity[1][2][3]. AG825 significantly accelerates apoptosis of human neutrophils[4]. AG-825 is a potential agent for overcoming Mn-induced neurotoxicity or AD development[5].

  • CAS Number: 149092-50-2
  • MF: C19H15N3O3S2
  • MW: 397.471
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 689.3±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 370.7±34.3 °C

Duligotuzumab

Duligotuzumab (MEHD-7945A; RG 7597) is a humanized IgG-κ monoclonal antibody that specifically targets Her3 (ErbB3)[1].

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

DPPY

DPPY (compound 6) is a potent PTK inhibitor with IC50 values of <10, <10, <10 nM for EGFR, BTK, JAK3, respectively. DPPY shows anti-proliferative activity against B-cell lymphoma cells. DPPY has the potential for the research of idiopathic pulmonary fibrosis (IPF)[1].

  • CAS Number: 2095883-62-6
  • MF: C25H26ClN7O3
  • MW: 507.97
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TK4g

TK4g is a Janus kinase (JAK) inhibitor with the IC50 values of 12.61 nM and 15.80 nM for JAK2 and JAK3, respectively. TK4g can be used in lymphoid-derived diseases and leukemia cancer research[1].

  • CAS Number: 2232890-86-5
  • MF: C19H19N3O4S
  • MW: 385.44
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(Rac)-Ruxolitinib D9

(Rac)-Ruxolitinib D9 ((Rac)-INCB18424 D9) is the deuterium labeled (Rac)-Ruxolitinib. (Rac)-Ruxolitinib is a JAK2 inhibitor[1].

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

HJC0152 free base

HJC0152 (free base) is an orally active and potent inhibitor of STAT3. HJC0152 (free base) inhibits cell cycle progression and induces apoptosis. HJC0152 (free base) significantly suppresses MDA-MB-231 xenograft tumor growth in mice[1].

  • CAS Number: 1420290-88-5
  • MF: C15H13Cl2N3O4
  • MW: 370.19
  • Catalog: Apoptosis
  • Density: 1.491±0.06 g/cm3(Predicted)
  • Boiling Point: 486.2±45.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

Sunvozertinib

Sunvozertinib is a potent ErbBs (EGFR, Her2, especially mutant forms) and BTK inhibitor. Sunvozertinib shows IC50s of 20.4, 20.4, 1.1, 7.5, and 80.4 nM for EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R and T790M mutations, and Her2 Exon20 YVMA, and EGFR WT A431, respectively (patent WO2019149164A1, example 52)[1].

  • CAS Number: 2370013-12-8
  • MF: C29H35ClFN7O3
  • MW: 584.08
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Brevilin A

Brevilin A is a sesquiterpene lactone isolated from Centipeda minima with anti-tumor activity. Brevilin A is a selective inhibitor of JAK-STAT signal pathway by attenuating the JAKs activity and blocking STAT3 signaling (IC50 = 10.6 µM) in Cancer Cells. Brevilin A induces apoptosis and autophagy via mitochondrial pathway and PI3K/AKT/mTOR inactivation in colon adenocarcinoma cell CT26[1][2].

  • CAS Number: 16503-32-5
  • MF: C20H26O5
  • MW: 346.417
  • Catalog: Apoptosis
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 494.0±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 216.0±28.8 °C

Ruxolitinib phosphate

Ruxolitinib phosphate is a potent JAK1/2 inhibitor with IC50s of 3.3 nM/2.8 nM, respectively, showing more than 130-fold selectivity over JAK3.

  • CAS Number: 1092939-17-7
  • MF: C17H21N6O4P
  • MW: 404.360
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-87

EGFR-IN-87 is a EGFR tyrosine kinase inhibitor. EGFR-IN-87 has IC50 value of 3.1 nM, 1.3 nM and 7.1 nM for EGFR_d746-750, EGFR_L858R/T790 and EGFR_WT in A431 cells, respectively. EGFR-IN-87 can be used for cancer diseases research[1].

  • CAS Number: 1835666-87-9
  • MF: C28H33N7O2
  • MW: 499.61
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SH-4-54

SH-4-54 is a most potent, small molecule, nonphosphorylated STAT inhibitor, with KDs of 300, 464 nM for STAT3 and STAT5, respectively.

  • CAS Number: 1456632-40-8
  • MF: C29H27F5N2O5S
  • MW: 610.592
  • Catalog: STAT
  • Density: 1.431±0.06 g/cm3
  • Boiling Point: 717.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 387.5±35.7 °C

Epitinib succinate

Epitinib succinate is an orally active and selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) designed for optimal brain penetration. Epitinib succinate can be used for the research of cancer[1][2].

  • CAS Number: 2252334-12-4
  • MF: C28H32N6O6
  • MW: 548.59
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tucatinib hemiethanolate

Tucatinib (Irbinitinib) hemiethanolate is a potent, orally active and selective HER2 inhibitor with an IC50 of 8 nM.

  • CAS Number: 1429755-56-5
  • MF: C26H24N8O2.1/2C2H6O
  • MW: 503.57
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-23

EGFR-IN-23 is a potent EGFR TKI (tyrosine kinase inhibitor) with an IC50 of 8.05 nM for BaF3/EGFR-DEL19/T790M/C797S cell (WO2021244502A1, compound 8)[1].

  • CAS Number: 2747133-37-3
  • MF: C36H44BrN10O3P
  • MW: 775.68
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SH-1028 mesylate

SH-1028 (mesylate) is a selective and oral active inhibitor of EGFR with an IC50 of 18 nM. SH-1028 (mesylate) exhibits potent activity against EGFR sensitive and resistant (T790 M) mutations. SH-1028 (mesylate) significantly inhibits proliferation of tumor cells with EGFR sensitive and resistant mutation[1].

  • CAS Number: 2180164-79-6
  • MF: C32H41N7O5S
  • MW: 635.78
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC 370284

NSC-370284 is a selective inhibitor of ten-eleven translocation 1 (TET1). NSC-370284 significantly inhibits the level of TET1 expression via targets STAT3/5. NSC-370284 has low cytotoxicity[1].

  • CAS Number: 116409-29-1
  • MF: C21H25NO6
  • MW: 387.42600
  • Catalog: STAT
  • Density: 1.276g/cm3
  • Boiling Point: 515.2ºC at 760mmHg
  • Melting Point: N/A
  • Flash Point: 265.4ºC

Pim1/AKK1-IN-1

Pim1/AKK1-IN-1 is a potent multi-kinase inhibitor with Kd values of 35 nM/53 nM/75 nM/380 nM for Pim1/AKK1/MST2/LKB1 respectively, and also inhibits MPSK1 and TNIK.

  • CAS Number: 1093222-27-5
  • MF: C20H13N5O
  • MW: 339.35000
  • Catalog: Pim
  • Density: 1.42
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Napabucasin

Napabucasin is a STAT3 inhibitor which blocks stem cell activity in cancer cells.

  • CAS Number: 83280-65-3
  • MF: C14H8O4
  • MW: 240.211
  • Catalog: STAT
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 444.4±45.0 °C at 760 mmHg
  • Melting Point: 226 °C
  • Flash Point: 216.4±21.4 °C

Epitinib

Epitinib is an orally active and selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) designed for optimal brain penetration. Epitinib can be used for the research of cancer[1][2].

  • CAS Number: 1203902-67-3
  • MF: C24H26N6O2
  • MW: 430.50
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Colivelin trifluoroacetate salt

Colivelin is a neuroprotective peptide and activator of STAT3.

  • CAS Number: 867021-83-8
  • MF: C119H206N32O35
  • MW: 2645.10000
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrphostin 47

Tyrphostin AG213 (AG213) is an inhibitor of epidermal growth factor receptor (EGFR) protein tyrosine kinase (IC50=0.85 μM). Tyrphostin AG213 inhibits tyrosine kinase activity IC50=2.4 μM) and topoisomerase II (IC100=50 μM). Tyrphostin AG213 can induce nonapoptotic cell programmed death in tumor cells[1][2][3].

  • CAS Number: 122520-86-9
  • MF: C10H8N2O2S
  • MW: 220.248
  • Catalog: Topoisomerase
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 474.5±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 240.8±31.5 °C

Picroside I

Picroside I is the major ingredient of Picrorhiza kurroa. Picrorhiza kurroa is a high value medicinal herb due to rich source of hepatoprotective metabolites, Picroside-I and Picroside-II[1]. Picroside I is a promising agent for the management of asthma. Picroside I reduces the inflammation significantly at its higher dose. Picroside I also downregulates pSTAT6 and GATA3 expressions. Picroside I dose-dependently increases the serum levels of IFN-γ[2].

  • CAS Number: 27409-30-9
  • MF: C24H28O11
  • MW: 492.473
  • Catalog: STAT
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 739.1±60.0 °C at 760 mmHg
  • Melting Point: 130 °C
  • Flash Point: 253.2±26.4 °C

Lestaurtinib

Lestaurtinib (CEP-701;KT-5555) is a multi-kinase inhibitor with potent activity against the Trk family of receptor tyrosine kinases. Lestaurtinib inhibits JAK2, FLT3 and TrkA with IC50s of 0.9, 3 and less than 25 nM, respectively.

  • CAS Number: 111358-88-4
  • MF: C26H21N3O4
  • MW: 439.463
  • Catalog: JAK
  • Density: 1.7±0.1 g/cm3
  • Boiling Point: 723.0±60.0 °C at 760 mmHg
  • Melting Point: 215-220ºC
  • Flash Point: 391.0±32.9 °C

PF 6274484

PF-6274484 is an inhibitor of the EGF receptor (EGFR; IC50s = 0.18 and 0.14 nM for wild-type EGFR and inhibitor-resistant EGFRL858R/T790M, respectively).

  • CAS Number: 1035638-91-5
  • MF: C18H14ClFN4O2
  • MW: 372.781
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 578.3±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 303.5±30.1 °C

MM-206

A novel small molecule STAT3 inhibitor that inhibits STAT3 DNA binding activity with IC50 of 1.16 uM, binds to the STAT3 coiled-coil domain (CCD); also inhibits G-CSF-induced STAT3 phosphorylation in AML cell lines with IC50 of 0.8-1.9 uM,

  • CAS Number: 1809581-87-0
  • MF: C22H12F5NO3S2
  • MW: 497.458
  • Catalog: STAT
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 601.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 317.8±34.3 °C

TMCB

CK2/ERK8-IN-1 is a dual casein kinase 2 (CK2) (Ki of 0.25 µM) and ERK8 inhibitor with IC50s of 0.50 μM. CK2/ERK8-IN-1 also binds to PIM1, HIPK2 (homeodomain-interacting protein kinase 2), and DYRK1A with Kis of 8.65 µM, 15.25 µM, and 11.9 µM, respectively. CK2/ERK8-IN-1 has pro-apoptotic efficacy[1].

  • CAS Number: 1085822-09-8
  • MF: C11H9Br4N3O2
  • MW: 534.82
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AS2863619 free base

AS2863619 free base enables conversion of antigen-specific effector/memory T cells into Foxp3+ regulatory T (Treg) cells for the treatment of various immunological diseases. AS2863619 free base is a potent, orally active cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor with IC50s of 0.61 nM and 4.28 nM, respectively. STAT5 activation enhanced by AS2863619 free base inhibition of CDK8/19, which consequently activates the Foxp3 gene[1].

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

Genistein

Genistein, a soy isoflavone, is a multiple tyrosine kinases inhibitor which acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis.

  • CAS Number: 446-72-0
  • MF: C15H10O5
  • MW: 270.237
  • Catalog: Apoptosis
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 555.5±50.0 °C at 760 mmHg
  • Melting Point: 297-298 °C
  • Flash Point: 217.1±23.6 °C

AG 99

(E)-AG 99 ((E)-Tyrphostin 46; (E)-Tyrphostin AG 99) is a potent EGFR inhibitor[1].

  • CAS Number: 122520-85-8
  • MF: C10H8N2O3
  • MW: 204.182
  • Catalog: EGFR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 544.4±50.0 °C at 760 mmHg
  • Melting Point: 231 °C
  • Flash Point: 283.0±30.1 °C

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