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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RET-IN-19

RET-IN-19 (compound 59) is a potent RET inhibitor, with IC50 values of 6.8 and 13.51 nM against RET-wt and RET V804M, respectively. RET-IN-19 shows anticancer activity. RET-IN-19 can be used for non-small cell lung cancer (NSCLC) research[1].

  • CAS Number: 2484919-71-1
  • MF: C28H28N6O4S
  • MW: 544.62
  • Catalog: Aurora Kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK1-IN-8

JAK1-IN-8, a potent JAK1 inhibitor (IC50<500 nM), compound 28, extracted from patent WO2016119700A1[1].

  • CAS Number: 1973485-18-5
  • MF: C22H23FN4O3S
  • MW: 442.51
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

FD1024

FD1024 is PIM inhibitor (IC50s: 1.96, 38.9, 4.17 nM for PIM1, 2, 3). FD1024 can be used for research of acute myeloid leukemia. FD1024 has strong antiproliferative activity against the tested AML cell lines, with 0.16 μM, 0.12 μM, 1.05 μM, 1.39μM for EOL-1, MV-4-11, KG-1, MOLM-16 cells. FD1024 also has antitumor efficacy in mice[1].

  • CAS Number: 1422456-47-0
  • MF: C21H20F2N4O2S
  • MW: 430.47
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZ-5104-d2

AZ-5104-d2 is the deuterium labeled AZ-5104. AZ-5104 is an EGFR inhibitor with IC50s of 1 nM, 6 nM, 1 nM, 25 nM and 7 nM for EGFRL858R/T790M, EGFRL858R, EGFRL861Q, EGFR and ErbB4, respectively[1].

  • CAS Number: 2719691-01-5
  • MF: C27H29D2N7O2
  • MW: 487.59
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

peruvoside

Peruvoside is a potent inhibitor of Src, PI3K, JNK, STAT, and EGFR. Peruvoside induces apoptosis and autophagy and possesses a broad spectrum of anticancer activity in breast, lung, liver cancers and leukemia. Peruvoside is a broad-spectrum and potent antiviral activity against positive-sense RNA viruses. Peruvoside sensitizes Gefitinib (HY-50895)-resistant tumour cells (A549, PC9/gef and H1975) to Gefitinib[1][2][3][4].

  • CAS Number: 1182-87-2
  • MF: C30H44O9
  • MW: 548.66
  • Catalog: Apoptosis
  • Density: 1.31g/cm3
  • Boiling Point: 731.6ºC at 760 mmHg
  • Melting Point: 161-164ºC
  • Flash Point: 236.2ºC

JAK3 Inhibitor VI

JI6 is a potent, selective and orally active FLT3 inhibitor, with IC50s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. JI6 also inhibits JAK3 and c-Kit, with IC50s of ∼250 and ∼500 nM, respectively. JI6 can be used for the research of acute myeloid leukemia[1].

  • CAS Number: 856436-16-3
  • MF: C19H17N3O4S
  • MW: 383.42100
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZD1208 hydrochloride

AZD1208 hydrochloride is a novel, orally bioavailable, highly selective PIM kinases inhibitor.

  • CAS Number: 1621866-96-3
  • MF: C21H22ClN3O2S
  • MW: 415.94
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

STAT3-IN-11

STAT3-IN-11 (7a) is a selective STAT3 inhibitor that inhibits the phosphorylation of STAT3 at site pTyr705. STAT3-IN-11 inhibits the phosphorylation of downstream genes (Survivin and Mcl-1) without affecting its upstream tyrosine kinases (Src and JAK2) levels and p-STAT1 expression. STAT3-IN-11 can induce cancer cell apoptosis, which is potential for the discovery of effective STAT3 inhibitors and antitumor agents against cancers[1].

  • CAS Number: 2503096-50-0
  • MF: C20H17NO4
  • MW: 335.35
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(4-CHLOROPHENYL)-2-[(PYRIDIN-4-YLMETHYL)AMINO]BENZAMIDE

VEGFR-IN-1 (compound 3) is a potent angiogenesis inhibitor with IC50s of 0.02, 0.18, 0.24 7.3, and 7 µM for KDR, Flt-1, c-Kit, EGF-R, and c-Src, respectively[1].

  • CAS Number: 269390-69-4
  • MF: C19H16ClN3O
  • MW: 337.80300
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Cenisertib

Cenisertib (AS-703569) is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3. Cenisertib induces major growth-inhibitory effects by blocking the activity of several different molecular targets in neoplastic mast cells (MC)[1]. Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia[2].

  • CAS Number: 871357-89-0
  • MF: C24H30FN7O
  • MW: 451.540
  • Catalog: Aurora Kinase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 708.3±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 382.2±35.7 °C

Lapatinib (GW572016)

Lapatinib (GW572016) is a potent EGFR and ErbB2 inhibitor with IC50s of 10.2 and 9.8 nM, respectively.

  • CAS Number: 231277-92-2
  • MF: C29H26ClFN4O4S
  • MW: 581.057
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 750.7±60.0 °C at 760 mmHg
  • Melting Point: 147 °C
  • Flash Point: 407.8±32.9 °C

BPIQ-I

BPIQ-I (PD 159121) is a potent and ATP-competitive EGFR tyrosine kinase inhibitor.. BPIQ-I shows anti-proliferative actively[1][2].

  • CAS Number: 174709-30-9
  • MF: C16H12BrN5
  • MW: 354.20400
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TC JL 37

TCJL37 is a potent, selective, and orally bioavailable TYK2 inhibitor with a Ki of 1.6 nM. TCJL37 can be used for the research of inflammatory bowel diseases (IBD)[1].

  • CAS Number: 1258294-34-6
  • MF: C17H11ClF2N4O2
  • MW: 376.74
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Istiratumab

Istiratumab (M-6495) is bispecific monoclonal antibody targeting IGF-1R and ErbB3. Istiratumab induces IGF-1R and ErbB3 receptor degradation through the proteasome pathway Istiratumab can be used for research of cancers[1][2][3].

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

W1131

W1131 is a potent STAT3 inhibitor, triggering ferroptosis. W1131 suppresses cancer progression in gastric cancer cell subcutaneous xenograft model, organoids model, and PDX model. W1131 effectively alleviates chemical resistance of cancer cells to 5-FU (HY-90006). W1131 regulates cell cycle, DNA damage response, and oxidative phosphorylation, including IL6-JAK-STAT3 pathway and ferroptosis pathway[1].

  • CAS Number: 2740522-79-4
  • MF: C23H19N5O4
  • MW: 429.43
  • Catalog: Ferroptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-54

EGFR-IN-54 (Compound 3c) is a potent EGFR inhibitor with an IC50 of 1.623 µM. EGFR-IN-54 shows cytotoxic activity against cancer cell lines[1].

  • CAS Number: 2418549-30-9
  • MF: C17H14N4O4S3
  • MW: 434.51
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HKI272 maleate

Neratinib (HKI-272) maleate is an orally available, irreversible, highly selective HER2 and EGFR inhibitor with IC50s of 59 nM and 92 nM, respectively[1].

  • CAS Number: 915942-22-2
  • MF: C34H33ClN6O7
  • MW: 673.115
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Erlotinib HCl (OSI-744)

Erlotinib hydrochloride inhibits purified EGFR kinase with an IC50 of 2 nM.

  • CAS Number: 183319-69-9
  • MF: C22H24ClN3O4
  • MW: 429.897
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: 553.6ºC at 760 mmHg
  • Melting Point: 223-225ºC
  • Flash Point: 288.6ºC

Nezutatug

Nezutatug is an anti-HER3 antibody, and used for cancer research[1].

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

Pacritinib hydrochloride

Pacritinib hydrochloride is a potent inhibitor of both wild-type JAK2 (IC50=23 nM) and JAK2V617F mutant (IC50=19 nM). Pacritinib hydrochloride also inhibits FLT3 (IC50=22 nM) and its mutant FLT3D835Y (IC50=6 nM). Pacritinib hydrochloride can be used for the research of acute myeloid leukemia (AML) and myelofibrosis (MF)[1][2][3].

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

Gefitinib

Gefitinib (ZD1839) is a EGFR tyrosine kinase inhibitor, with IC50 of 2-37 nM in NR6wtEGFR cells.

  • CAS Number: 184475-35-2
  • MF: C22H24ClFN4O3
  • MW: 446.902
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 586.8±50.0 °C at 760 mmHg
  • Melting Point: 119-1200C
  • Flash Point: 308.7±30.1 °C

BP-1-102

BP-1-102 is an orally available, small-molecule inhibitor of transcription factor Stat3, with an IC50 of 6.8 μM.

  • CAS Number: 1334493-07-0
  • MF: C29H27F5N2O6S
  • MW: 626.591
  • Catalog: STAT
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 749.2±70.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 406.9±35.7 °C

PKI 166 hydrochloride

PKI-166 hydrochloride is a potent, selective and orally bioavailable EGFR tyrosine kinase inhibitor, with an IC50 of 0.7 nM[1].

  • CAS Number: 2230253-82-2
  • MF: C20H19ClN4O
  • MW: 366.84
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

MNK8

MNK8 is a potent STAT3 (signal transducer and activator of transcription 3) inhibitor. MNK8 inhibits STAT3 activation and reduced its DNA binding ability. MNK8 shows good growth inhibition against hepatocellular carcinoma (HCC) cells. MNK8 induces apoptosis in HCC cells. MNK8 reduces prosurvival proteins expression and migration/invasion of HCC cells[1].

  • CAS Number: 2055078-49-2
  • MF: C15H12N2O2
  • MW: 252.27
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Deuruxolitinib

Deuruxolitinib (CTP-543), a deuterated Ruxolitinib, modulates the activity of JAK1/JAK2. Deuruxolitinib can be used for the research hair loss disorders (from patent WO2017192905A1, compound I)[1].

  • CAS Number: 1513883-39-0
  • MF: C17H10D8N6
  • MW: 314.41
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(3,4,5-Trihydroxybenzylidene)malononitrile

Tyrphostin 25 (AG82) is a specific inhibitor of the EGFR tyrosine kinase. Tyrphostin 25 is also a GPR35 agonist with an IC50 of 0.94 µM and an EC50 of 5.3 µM[1][2].

  • CAS Number: 118409-58-8
  • MF: C10H6N2O3
  • MW: 202.17
  • Catalog: EGFR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 500.8±50.0 °C at 760 mmHg
  • Melting Point: -220ºC dec.
  • Flash Point: 256.7±30.1 °C

Disitamab

Disitamab (RC48-0) is a humanized monoclonal antibody targeting HER2. Disitamab can be used in the synthesis of antibody-drug conjugates (ADCs), Disitamab vedotin (Disitamab vedotin (HY-P9985))[1].

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

Bafisontamab

Bafisontamab (EMB-01) is a bispecific antibody targeting EGFR and cMET with antitumor activity[1].

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

ROCK2-IN-7

ROCK2-IN-7 is a kinase inhibitor targeting to ROCK2. ROCK2-IN-7 inhibits ROCK2/pSTAT3 Signaling. ROCK2-IN-7 suppresses systemic immunity activation and attenuates inflammation in psoriasis model[1].

  • CAS Number: 3000541-95-4
  • MF: C26H28FN5O
  • MW: 445.53
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-53

EGFR-IN-53 (Compound 7) is a potent EGFR inhibitor with an IC50 of 8.264 µM. EGFR-IN-53 shows cytotoxic activity against cancer cell lines[1].

  • CAS Number: 2418549-33-2
  • MF: C14H13N3O2S
  • MW: 287.34
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A