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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Peficitinib hydrochloride

Peficitinib (ASP015K) hydrochloride is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively[1].

  • CAS Number: 1353219-06-3
  • MF: C18H23ClN4O2
  • MW: 362.85
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HOOBT

HODHBt (HOOBt) inhibits STAT5-SUMO interaction by blocking SUMOylation of phosphorylated STAT5. HODHBt enhances the magnitude of IL-15 signaling and significantly increases the natural killer (NK) cell cytotoxicity phenotype and function and the generation of cytokine-induced memory-like (CIML) natural killer (NK) cells. HODHBt can be used for research of HIV-infection and cancer[1].

  • CAS Number: 28230-32-2
  • MF: C7H5N3O2
  • MW: 163.133
  • Catalog: HIV
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 348.7±25.0 °C at 760 mmHg
  • Melting Point: 184-189°C
  • Flash Point: 164.7±23.2 °C

ENMD-119

ENMD-119 is a 2-methoxyestradiol analogue with antiproliferative and antiangiogenic activity, and is suitable for inhibiting HIF-1α and STAT3 in human HCC cells.

  • CAS Number: 864668-87-1
  • MF: C20H25NO2
  • MW: 311.41800
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-5

EGFR-IN-5 is a EGFR inhibitor with IC50s of 10.4, 1.1, 34, 7.2 nM for EGFR, EGFRL858R, EGFRL858R/T790M, and EGFRL858R/T790M/C797S, respectively.

  • CAS Number: 2225887-26-1
  • MF: C31H38FN9O
  • MW: 571.69
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Delphinidin-3-O-glucoside chloride

Delphinidin 3-glucoside chloride (Delphinidin 3-O-glucoside chloride) is an active anthocyanin found in bilberry extract. Delphinidin 3-glucoside chloride induces a pro-apoptotic effect in B cell chronic lymphocytic leukaemia (B CLL)[1]. Delphinidin 3-glucoside chloride exerts phytoestrogen activity by binding to ERβ, with an IC50 of 9.7 μM[2]. Delphinidin-3-O-glucoside chloride inhibits EGFR with an IC50 of 2.37 µM[3].

  • CAS Number: 6906-38-3
  • MF: C21H21ClO12
  • MW: 500.837
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Peficitinib hydrobromide

Peficitinib (ASP015K) hydrobromide is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

  • CAS Number: 1353219-05-2
  • MF: C18H23BrN4O2
  • MW: 407.30
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Mal-VC-PAB-(N-Me-amide-C3)-ADU-S100 triethylamine

Mal-VC-PAB-(N-Me-amide-C3)-ADU-S100 triethylamine is an immune stimulator antibody conjugate (ISAC) comprising an anti-human epidermal growth factor receptor 2 (HER2) antibody, a STING agonist (ADU-S100) and a linker. Mal-VC-PAB-(N-Me-amide-C3)-ADU-S100 triethylamine can be uesd for cancer research (WO2018200812A1; example 5)[1].

  • CAS Number: 2249935-19-9
  • MF: C51H65N17O19P2S2.xC6H15N
  • MW:
  • Catalog: STING
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZ-3

AZ-3 is a potent and selective JAK1 inhibitor with an IC50 of 34 nM.

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

PF-06700841 P-Tosylate

PF-06700841 P-Tosylate is a dual JAK1 and TYK2 inhibitor with IC50s of 17 and 23 nM, respectively. Anti-inflammatory activity[1].

  • CAS Number: 2140301-96-6
  • MF: C25H29F2N7O4S
  • MW: 561.60
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EMI1

EMI1 is an EGFR ex19del/T790M/C797S and EGFR L858R/T790M/C797S inhibitor[1].

  • CAS Number: 35773-42-3
  • MF: C20H18N2O3
  • MW: 334.36900
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Theliatinib tartrate

Theliatinib (Xiliertinib) tartrate is a potent, ATP-competitive, orally active and highly selective EGFR inhibitor with a Ki of 0.05 nM and an IC50 of 3 nM. Theliatinib has an IC50 of 22 nM for EGFR T790M/L858R mutant. Theliatinib shows >50-fold selectivity for EGFR than other kinases[1].

  • CAS Number: 2413487-72-4
  • MF: C29H32N6O8
  • MW: 592.60
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S)-Sunvozertinib

(S)-Sunvozertinib ((S)-DZD9008), the S-enantiomer of Sunvozertinib, shows inhibitory activity against EGFR exon 20 NPH and ASV insertions, EGFR L858R/T790M mutation and Her2 exon20 YVMA insertion (IC50=51.2 nM, 51.9 nM, 1 nM, and 21.2 nM, respectively). (S)-Sunvozertinib also inhibits BTK[1].

  • CAS Number: 2370013-49-1
  • MF: C29H35ClFN7O3
  • MW: 584.08
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cucurbitacin I

Cucurbitacin I is a natural selective inhibitor of JAK2/STAT3, with potent anti-cancer activity.

  • CAS Number: 2222-07-3
  • MF: C30H42O7
  • MW: 514.650
  • Catalog: STAT
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 716.9±60.0 °C at 760 mmHg
  • Melting Point: 148-150ºC
  • Flash Point: 401.3±29.4 °C

EGFR/HER2-IN-5

EGFR/HER2-IN-5 (compound 6h) is an orally active irreversible dual inhibitor. EGFR/HER2-IN-5 inhibits EGFR with an IC50 value of 1.01 nM and demonstrates potent EGFR kinase inhibitory activities on L858R and T790M mutations. EGFR/HER2-IN-5 has potent antitumor efficacy in vivo and can be used for lung cancer research[1].

  • CAS Number: 1879071-97-2
  • MF: C30H33ClN6O4
  • MW: 577.07
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GW2974

GW2974 is a potent dual inhibitor of EGFR and HER2 with IC50 value of 0.007 μM and 0.016 μM, respectively. GW2974 demonstrates in vitro inhibition of the EGFR and HER2 and inhibits the growth of tumor cell. GW2974 can be used for glioblastoma multiforme (GBM) disease research[1][2].

  • CAS Number: 202272-68-2
  • MF: C23H21N7
  • MW: 395.46
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: 645.6ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 344.3ºC

EGFR/CDK2-IN-1

EGFR/CDK2-IN-1 (Compound 3b) is an EGFR/CDK2 inhibitor. EGFR/CDK2-IN-1 shows good cytotoxicity against MCF7 and HepG2 cells. EGFR/CDK2-IN-1 can be used in cancer research[1].

  • CAS Number: 2841405-96-5
  • MF: C19H12BrClO2
  • MW: 387.65
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Neratinib-d6

Neratinib-d6 (HKI-272-d6) is the deuterium labeled Neratinib. Neratinib (HKI-272) is an orally available, irreversible tyrosine kinase inhibitor with IC50s of 59 nM and 92 nM for HER2 and EGFR, respectively.

  • CAS Number: 1259519-18-0
  • MF: C30H23D6ClN6O3
  • MW: 563.08
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tofacitinib (CP-690550) Citrate

Tofacitinib citrate is a JAK1/2/3 inhibitor with IC50s of 1, 20, and 112 nM, respectively.

  • CAS Number: 540737-29-9
  • MF: C22H28N6O8
  • MW: 504.493
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Nelipepimut-S

Nelipepimut-S is a peptide vaccine which targets HER2. Nelipepimut-S has immune activity against HER2 positive breast cancer[1].

  • CAS Number: 160212-35-1
  • MF: C50H78N10O11
  • MW: 995.215
  • Catalog: EGFR
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 1354.5±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 773.0±34.3 °C

Timigutuzumab

Timigutuzumab (GEXMab73) is a humanized monoclonal antibody that targets ErbB2. Timigutuzumab can be used for the research of cancer[1].

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

EGFR/HER2/TS-IN-2

EGFR/HER2/TS-IN-2 (compound 17) is a potent EGFR/HER2 and TS (Thymidylate synthase) inhibitor, with IC50 values of 0.173, 0.125, and 1.12 μM, respectively. EGFR/HER2/TS-IN-2 shows cytotoxic activity against MDA-MB-231 cancer cell lines, with an IC50 of 1.69 µM[1].

  • CAS Number: 2444364-04-7
  • MF: C26H21N7OS2
  • MW: 511.62
  • Catalog: Thymidylate Synthase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

IBL-302

IBL-302 (AMU302) is an orally available dual-signaling inhibitor of PIM and PI3K/AKT/mTOR with activity against breast cancer and neuroblastoma. IBL-302 demonstrated in vivo efficacy in a nude mouse xenograft model, inhibiting trastuzumab (HY-P9907) resistance challenges. IBL-302 also enhances the effects of common cytotoxic chemotherapy drugs cisplatin (HY-17394), doxorubicin (HY-15142A), and etoposide (HY-13629)[1][2][3].

  • CAS Number: 1414455-21-2
  • MF: C25H18FN5O4S3
  • MW: 567.63
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A