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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Fedratinib(SAR302503,TG101348)

Fedratinib (TG-101348) is a selective inhibitor of JAK2 with an IC50 of 3 nM, showing 35- and 334-fold selectivity over JAK1 and JAK3, respectively.

  • CAS Number: 936091-26-8
  • MF: C27H36N6O3S
  • MW: 524.678
  • Catalog: JAK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 713.7±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 385.5±35.7 °C

EGFR-IN-28

EGFR-IN-28 is a potent EGFR inhibitor. EGFR-IN-28 has antitumor activity[1].

  • CAS Number: 2754392-31-7
  • MF: C31H39BrN10O3S
  • MW: 711.68
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Patritumab

Patritumab (Human Anti-ERBB3 Recombinant Antibody) is a neutralizing monoclonal antibody to ERBB3. Patritumab shows a synergy with Cetuximab (HY-P9905), potently inhibits the phosphorylation of EGFR, HER2, HER3, ERK, and Akt. Patritumab also induces cell apoptosis and suppresses the growth of pancreatic, non-small cell lung cancer, and colorectal cancer xenograft tumors[1].

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

Stattic

Stattic is a potent inhibitor of STAT3 activation and dimerization.

  • CAS Number: 19983-44-9
  • MF: C8H5NO4S
  • MW: 211.195
  • Catalog: STAT
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 461.1±45.0 °C at 760 mmHg
  • Melting Point: 184ºC
  • Flash Point: 232.6±28.7 °C

INCB053914

INCB053914 (INCB-053914) is a novel potent, and selective ATP-competitive, pan-PIM kinase inhibitor with IC50 of 0.24/30.0/0.12 nM for PIM1/2/3, respectively; INCB053914 is highly selective against a panel of more than 50 kinases (>475-fold selectivity) with exception of RSK2 (IC50=7.1 uM); inhibits cellular proliferation in a panel of cell lines derived from hematologic malignancies including AML, MM, DLBCL, MCL, and T-ALL with GI50 of <100 nM, inhibits proliferation in all MM cell lines with GI5050 of 13.2-230.0 nM; inhibits PIM kinase-mediated phosphorylation of BAD in MOLM-16 and KMS-12-BM cells with IC50 of 4 and 27 nM, also increases PIM2 expression in KG-1a (AML), Pfeiffer, and KMS12-PE cells; in vivo, INCB053914 inhibited Bcl-2-associated death promoter protein phosphorylation and dose-dependently inhibited tumor growth in acute myeloid leukemia and multiple myeloma xenografts. Solid Tumors Phase 2 Clinical

  • CAS Number: 1620012-39-6
  • MF: C26H26F3N5O3
  • MW: 513.521
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AS1810722

AS1810722 is an orally active and potent STAT6 inhibitor with an IC50 of 1.9 nM. AS1810722 shows a good profile of CYP3A4 inhibition. AS1810722, a derivative of fused bicyclic pyrimidine, has the potential for allergic diseases such as asthma and atopic diseases research[1].

  • CAS Number: 909561-15-5
  • MF: C25H25F2N7O
  • MW: 477.51
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Afatinib oxalate

Afatinib (BIBW 2992) oxalate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC50 values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively. Afatinib oxalate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer[1][2][3][4].

  • CAS Number: 1398312-64-5
  • MF: C26H27ClFN5O7
  • MW: 575.97
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR mutant-IN-2

EGFR mutant-IN-2 (Compound D51) is an EGFR mutant inhibitor. EGFR mutant-IN-2 inhibits the EGFRL858R/T790M/C797S mutant with an IC50 value of 14 nM. EGFR mutant-IN-2 inhibits the EGFRdel19/T790M/C797S mutant with an IC50 value of 62 nM. EGFR mutant-IN-2 has favorable PK parameters, safety properties, in vivo stability, and antitumor activity[1].

  • CAS Number: 2770009-06-6
  • MF: C27H27F3N6O2S
  • MW: 556.60
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nitidine chloride

Nitidine chloride, a potential anti-malarial lead compound derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through diverse pathways, including inducing apoptosis, inhibiting STAT3 signaling cascade, DNA topoisomerase 1 and 2A, ERK and c-Src/FAK associated signaling pathway. Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kB pathway[1][2][3][4][5][6].

  • CAS Number: 13063-04-2
  • MF: C21H18ClNO4
  • MW: 383.825
  • Catalog: Apoptosis
  • Density: 1.35g/cm3
  • Boiling Point: 619ºC at 760 mmHg
  • Melting Point: 281-282ºC
  • Flash Point: 189.4ºC

UNC-CA359

UNC-CA359 is a potent epidermal growth factor receptor (EGFR) inhibitor, with an IC50 value of 18 nM. UNC-CA359 exhibits strong anti-tumor activity, can be used to Chordoma research[1].

  • CAS Number: 2676156-05-9
  • MF: C18H14ClN3O2
  • MW: 339.78
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PIM447

PIM447 is novel pan-PIM kinase inhibitor, including Moloney Murine Leukemia (PIM) 1, 2, and 3 Kinase.target: pan-PIM inhibitor [2] [3]In vitro: PIM447 is cytotoxic for myeloma cells due to cell cycle disruption and induction of apoptosis mediated by a decrease in phospho-Bad (Ser112) and c-Myc levels and the inhibition of mTORC1 pathway. PIM447 also inhibits in vitro osteoclast formation and resorption, downregulates key molecules involved in these processes and partially disrupts the F-actin ring, while increasing osteoblast activity and mineralization.[1]In vivo: PIM447 significantly reduces the tumor burden and preventes tumor-associated bone loss in a disseminated murine model of human myeloma.[1]

  • CAS Number: 1210608-43-7
  • MF: C24H23F3N4O
  • MW: 440.461
  • Catalog: Pim
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 493.7±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 252.4±28.7 °C

ZT55

ZT55 (JAK inhibitor ZT55) is a novel potent, highly-selective tyrosine kinase JAK2 inhibitor with IC50 of 31 nM; displays no significant activity against JAK1/3 (IC50>10 uM); exhibits potent effects on the cellular JAK-STAT pathway, inhibiting tyrosine phosphorylation in JAK2V617F and downstream STAT3/5 transcription factors; inhibits the proliferation of the JAK2V617F-expressing HEL cell line, leading to cell cycle arrest at the G2/M phase and induction of caspase-dependent apoptosis; significantly suppressed the growth of HEL xenograft tumors in vivo, blocks erythroid colony formation of peripheral blood hematopoietic progenitors from patients carrying the JAK2V617F mutation.

  • CAS Number: 2138488-38-5
  • MF: C17H16N2O3
  • MW: 296.326
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Lapatinib-d5

Lapatinib-d5 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: 2748212-14-6
  • MF: C29H21D5ClFN4O4S
  • MW: 586.09
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TCS 21311

TCS 21311 (NIBR3049) is a potent, highly selective JAK3 inhibitor with an IC50 of 8 nM, it displays >100-fold selectivity over JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ, and GSK3β with IC50s of 13, 68, and 3 nM, respectively[1].

  • CAS Number: 1260181-14-3
  • MF: C27H25F3N4O4
  • MW: 526.50700
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gefitinib dihydrochloride

Gefitinib (ZD 1839) dihydrochloride is a potent, selective and orally active EGFR tyrosine kinase inhibitor with an IC50 of 33 nM. Gefitinib dihydrochloride selectively inhibits EGF-stimulated tumor cell growth (IC50 of 54 nM) and blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Gefitinib dihydrochloride also induces autophagy and cell apoptosis, which can be used for cancer related research, such as Lung cancer and breast cancer [1][2][5].

  • CAS Number: 184475-56-7
  • MF: C22H26Cl3FN4O3
  • MW: 519.824
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: 628.2ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 333.7ºC

Danvatirsen

Danvatirsen is an antisense oligonucleotide targeting STAT3 with potential antitumor activity. Danvatirsen binds to STAT3 mRNA, thereby inhibiting translation of the transcript. Suppression of STAT3 expression induces tumor cell apoptosis and decreases tumor cell growth.

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

EGFR-IN-9

EGFR-IN-9 (Compound 8) is a potent EGFR kinase inhibitor with IC50s of 7 nM, 28 nM for the wild type EGFR kinase and double mutant EGFR kinase (L858R/T790M). EGFR-IN-9 has antitumor activity[1].

  • CAS Number: 1226549-39-8
  • MF: C29H24N4O3
  • MW: 476.53
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Isoprocurcumenol

Isoprocurcumenol is a guaiane type sesquiterpene, that can be isolated from Curcuma comosa. Isoprocurcumenol can activate EGFR signaling. Isoprocurcumenol increases the phosphorylation of ERK and Akt. Isoprocurcumenol promotes the proliferation of keratinocytes[1][2][3].

  • CAS Number: 102130-90-5
  • MF: C15H22O2
  • MW: 234.334
  • Catalog: EGFR
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 360.3±41.0 °C at 760 mmHg
  • Melting Point: 99.5-100.5 ºC (hexane )
  • Flash Point: 153.7±20.2 °C

PF-06263276

PF-06263276 (PF 6263276) is a potent and selective pan-JAK inhibitor, with IC50s of 2.2 nM, 23.1 nM, 59.9 nM and 29.7 nM for JAK1, JAK2, JAK3 and TYK2, respectively[1].

  • CAS Number: 1421502-62-6
  • MF: C31H31FN8O2
  • MW: 566.638
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

niclosamide sodium salt

Niclosamide (BAY2353) sodium is an orally active antihelminthic agent used in parasitic infection research[1]. Niclosamide sodium is a STAT3 inhibitor with an IC50 of 0.25 μM in HeLa cells[4]. Niclosamide sodium has biological activities against cancer, and inhibits DNA replication in Vero E6 cells[2][3][5].

  • CAS Number: 40321-86-6
  • MF: C13H7Cl2N2NaO4
  • MW: 349.10100
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/C797S-IN-1

EGFR/C797S-IN-1 is a potent EGFR-C797S inhibitor with an IC50 value of 0.128 µM. EGFR/C797S-IN-1 shows anti-proliferative activity and anti-tumor activity. EGFR/C797S-IN-1 inhibits the expression of p-EGFR in a dose-dependent manner[1].

  • CAS Number: 2378188-21-5
  • MF: C28H30N4O3
  • MW: 470.56
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Petosemtamab

Petosemtamab (MCLA 158) is an anti- EGFR (Kd: 0.22 nM) and anti-LGR5 (Kd: 0.86 nM) monoclonal antibody (mAb). Petosemtamab leads to EGFR signaling blockade and receptor degradation in LGR5+ cancer cells. Petosemtamab can be used in the research of solid tumors, such as head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer (CRC)[1][2].

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

Upadacitinib tartrate

Upadacitinib (ABT-494) tartrate tetrahydrate is a potent, orally active and selective Janus kinase 1 (JAK1) inhibitor (IC50=43 nM). Upadacitinib tartrate tetrahydrate displays approximately 74 fold selective for JAK1 over JAK2 (200 nM) in cellular assays dependent on specific, relevant cytokines. Upadacitinib tartrate tetrahydrate can be used for several autoimmune disorders research[1][2].

  • CAS Number: 1607431-21-9
  • MF: C21H33F3N6O11
  • MW: 602.516
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Eupalinolide K

Eupalinolide K, a sesquiterpene lactones compound from Eupatorium lindleyanum, is a STAT3 inhibitor. Eupalinolide K is a Michael reaction acceptor (MRA) [1].

  • CAS Number: 108657-10-9
  • MF: C20H26O6
  • MW: 362.417
  • Catalog: STAT
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 574.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 201.5±23.6 °C

JAK-2/3-IN-2

JAK-2/3-IN-2 (Compound 3h) is a JAK2 and JAK3 inhibitor with IC50s of 23.85 nM and 18.9 nM, respectively[1].

  • CAS Number: 2170398-48-6
  • MF: C19H19ClN2OS
  • MW: 358.88
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Itacnosertib

Itacnosertib (TP-0184) is both inhibitor to JAK2, ACVR1 (ALK2) and ALK5 as described in WO2014151871[1].

  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 675.4±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 362.2±34.3 °C

Daphnetin

Daphnetin (7,8-dihydroxycoumarin), one coumarin derivative isolated from plants of the Genus Daphne, is a protein kinase inhibitor, with IC50s of 7.67 μM, 9.33 μM and 25.01 μM for EGFR, PKA and PKC in vitro, respectively[1][2]. Daphnetin (7,8-dihydroxycoumarin) is a secondary metabolite of plants used in folk medicine to counter inflammatory and allergic diseases, also has been clinically used in the treatment of coagulation disorders, rheumatoid arthritis with anti-malarian and anti-pyretic properties[3].

  • CAS Number: 486-35-1
  • MF: C9H6O4
  • MW: 178.14
  • Catalog: PKC
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 430.4±45.0 °C at 760 mmHg
  • Melting Point: 265-268°C (dec.)
  • Flash Point: 184.5±22.2 °C

Tyk2-IN-4(BMS986165)

Tyk2-IN-4 is a selective, potent, allosteric inhibitor of tyrosine kinase 2 (Tyk2).

  • CAS Number: 1609392-27-9
  • MF: C20H19D3N8O3
  • MW: 425.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rovadicitinib

Rovadicitinib is a Janus kinase (JAK) inhibitor with an IC50 value <20 nM. Rovadicitinib also exhibits anti-inflammatory activity[1][2].

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

JAK-IN-30

JAK-IN-30 (compound 31) is a water-soluble JAK inhibitor with IC50 values of 2, 15, 18 and 2 nM for JAK2, JAK1, JAK3 and TYK2, respectively. JAK-IN-30 has research potential for dry eye disease (DED)[1].

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