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-447 dihydrochloride

PIM447 is a pan-PIM kinase ihibitor with Kis of 6, 18, 9 nM for PIM1, PIM2 and PIM3, respectively.

  • CAS Number: 1820565-69-2
  • MF: C24H25Cl2F3N4O
  • MW: 513.383
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NT219

NT219 is a potent and dual inhibitor of insulin receptor substrates 1/2 (IRS1/2) and STAT3. IRS1/2 and STAT3 are major signaling junctions regulated by various oncogenes. NT219 affects IRS1/2 degradation and inhibits STAT3 phosphorylation. NT219 has the potential for the research of cancer diseases[1].

  • CAS Number: 1198078-60-2
  • MF: C16H14BrNO5S
  • MW: 412.26
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Erlotinib-13C6 hydrochloride

Erlotinib-13C6 (hydrochloride) is the 13C labeled Erlotinib Hydrochloride[1]. Erlotinib Hydrochloride (CP-358774 Hydrochloride) inhibits purified EGFR kinase with an IC50 of 2 nM[2].

  • CAS Number: 1210610-07-3
  • MF: C22H24ClN3O4
  • MW: 435.85300
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

UC-514321

UC-514321 is a more effective analog of NSC-370284 that directly binds to STAT3/5, significantly and selectively suppresses the viability of AML cells with high level of TET1 expression both in vitro and in vivo; shows no inhibitory effect on the viability of TET1-low AML (i.e., NB4) cells, function as TET1-transcription inhibitor in TET1-high AMLs and the anti-leukemic effects are TET1-dependent.

  • CAS Number: 299420-83-0
  • MF: C26H35NO5
  • MW: 441.568
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrosine kinase-IN-7

Tyrosine kinase-IN-7 (compound 13h) is an inhibitor of the tyrosine kinase EGFR. The IC50s for inhibiting EGFR(WT) and EGFR(T790M) are 0.630 μM and 0.956 μM respectively. Tyrosine kinase-IN-7 has antitumor activity against four cancer cell lines (HepG2, HCT-116, MCF-7, and A431) with IC50s of 13.02 μM, 10.14 μM, 12.68 μM, and 47.05 μM, respectively[1].

  • CAS Number: 345615-74-9
  • MF: C16H15N3OS
  • MW: 297.375
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 525.2±45.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 271.5±28.7 °C

MNK/PIM-IN-1

MNK/PIM-IN-1 represents an innovative dual MNK/PIM inhibitor with a good pharmacokinetic profile.

  • CAS Number: 2430792-91-7
  • MF: C27H27FN6O2
  • MW: 486.54
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HDS 029

EGFR/ErbB-2/ErbB-4 inhibitor-3 (compound 29) is a potent tyrosine kinase inhibitor with IC50s of 0.3, 1.1, 0.5, 2.5, 24 nM for erbB1, erbB2, erbB4, EGF, HER, respectively[1].

  • CAS Number: 881001-19-0
  • MF: C17H11ClFN5O
  • MW: 355.75400
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Becotatug

Becotatug (JMT-101) is an IgG1 antibody targeting EGFR that can also be conjugated to Afatinib (HY-10261) and Osimertinib (HY-15772) as a synthetic ADC[1].

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

FGFR2-IN-3

FGFR2-IN-3 is an orally active selective inhibitor of FGFR2[1].

  • CAS Number: 2549174-42-5
  • MF: C28H24FN7O2
  • MW: 509.53
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Erlotinib-d6

Erlotinib D6 (CP-358774 D6) is a deuterium labeled Erlotinib (CP-358774). Erlotinib is a directly acting inhibitor EGFR tyrosine kinase inhibitor with an IC50 of 2 nM for human EGFR[1].

  • CAS Number: 1034651-23-4
  • MF: C22H17D6N3O4
  • MW: 399.47
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

L002

L002 is a novel potent, specific acetyltransferase p300 (KAT3B) inhibitor with an IC50 of 1.98 uM. L002 has weak inhibitory effects against PCAF and GCN5 (IC50s =35 and 34 µM, respectively) and is specific for p300 over a panel of additional acetyltransferases, deacetylases, and methyltransferases[1]. L002 blocks histone acetylation and p53 acetylation, and inhibits STAT3 activation[2].

  • CAS Number: 321695-57-2
  • MF: C15H15NO5S
  • MW: 321.348
  • Catalog: Histone Acetyltransferase
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 459.8±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 231.9±31.5 °C

HJ-PI01

HJ-PI01 (10-Acetylphenoxazine) is an orally active Pim-2 inhibitor. HJ-PI01 induces apoptosis and autophagic cell death of cancer cells. HJ-PI01 inhibits tumor growth in MDA-MB-231 xenograft mice. HJ-PI01 can be used for cancer research[1].

  • CAS Number: 6192-43-4
  • MF: C14H11NO2
  • MW: 225.24300
  • Catalog: Pim
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-27

EGFR-IN-27 is a potent EGFR inhibitor with IC50s of <50 nM for EGFR Del, L858R, Del/T790M, L858R/T790M, Del/T790M/C797S, and L858R/T790M/C797S, respectively (WO2021249324A1, compound 511)[1].

  • CAS Number: 2752328-62-2
  • MF: C35H46N9O2P
  • MW: 655.77
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Artesunate-d4

Artesunate-d4 is deuterium labeled Artesunate. Artesunate is an inhibitor of both STAT-3 and exported protein 1 (EXP1).

  • CAS Number: 1316753-15-7
  • MF: C19H24D4O8
  • MW: 388.45
  • Catalog: Ferroptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 507.1±50.0 °C at 760 mmHg
  • Melting Point: 130-132°C
  • Flash Point: 175.6±23.6 °C

Beta-Hydroxyisovalerylshikonin

Beta-hydroxyisovalerylshikonin is a natural product isolated from Lithospermium radix, acts as a potent inhibitor of protein tyrosine kinases (PTK), with IC50s of 0.7μM and 1μM for EGFR and v-Src receptor, respectively. Beta-hydroxyisovalerylshikonin is effective against a wide variety of tumor cell lines, and most efficiently induces cell-death in NCI-H522 and DMS114 cells[1].

  • CAS Number: 7415-78-3
  • MF: C21H24O7
  • MW: 388.41100
  • Catalog: EGFR
  • Density: 1.312g/cm3
  • Boiling Point: 616.9ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 215.8ºC

HS-10296

HS-10296 is an orally available inhibitor of the epidermal growth factor receptor (EGFR) mutant form T790M, with potential antineoplastic activity.

  • CAS Number: 1899921-05-1
  • MF: C30H36ClN7O2
  • MW: 562.11
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK2-IN-9

JAK2-IN-9 (Compound A8) is a selective JAK2 inhibitor (IC50: 5 nM). JAK2-IN-9 inhibits the phosphorylation of JAK2, STAT3, and STAT5. JAK2-IN-9 has metabolic stabilities. JAK2-IN-9 induces apoptosis. JAK2-IN-9 can be used for research of myeloproliferative neoplasms (MPNs)[1].

  • CAS Number: 2568842-26-0
  • MF: C20H24N6O2S
  • MW: 412.51
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WSD0922

WSD-0922 is a potent, selective, orally active, and BBB penetrable EGFR/EGFRVIII inhibitor. WSD-0922 is against EGFRm+ (EGFRvIII/Del19/L858R) with an IC50 of <10 nM. WSD0922 shows good safety profile and preclinical anti-tumor efficacy[1].

  • CAS Number: 2226552-64-1
  • MF: C23H21F3N4O2
  • MW: 442.43
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrphostin AG 835

(+)-Tyrphostin B44 (Tyrphostin AG 835) (Compound B50) is an EGRF inhibitor with antitumor activities[1].

  • CAS Number: 133550-37-5
  • MF: C18H16N2O3
  • MW: 308.33100
  • Catalog: EGFR
  • Density: 1.299g/cm3
  • Boiling Point: 603ºC at 760mmHg
  • Melting Point: 146 °C
  • Flash Point: 318.5ºC

RTC-5

RTC-5 is an optimized phenothiazine with anti-cancer potency. RTC-5 demonstrates efficacy against a xenograft model of an EGFR driven cancer, its effects is attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling[1].

  • CAS Number: 1423077-49-9
  • MF: C24H22ClF3N2O3S
  • MW: 510.96
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Izalontamab

Izalontamab (SI-B001) is a bispecific anti-EGFR/HER3 monoclonal antibody with high selectivity for EGFR/HER3 heterodimer. Izalontamab can be used for the research of cancer[1].

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

STAT3-IN-20

STAT3-IN-20 (Compound 40) is a selective STAT3 inhibitor (IC50: 0.65 μM). STAT3-IN-20 binds the SH2 domain to inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. STAT3-IN-20 exhibits antiproliferative activities against STAT3-overactivated DU145 and MDA-MB-231 cancer cells (IC50: 2.97 μM and 3.26 μM respectively). STAT3-IN-20 induces cell cycle arrest and apoptosis[1].

  • CAS Number: 2768427-54-7
  • MF: C30H27F4N7S
  • MW: 593.64
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ertumaxomab

Ertumaxomab (Anti-Human CD22 Recombinant Antibody) is a bispecific antibody targeting HER2/neu and CD3. Ertumaxomab activates Fcγ type I/III-receptors, forming a tri-cell complex among tumour cell, T cell and accessory cell. Ertumaxomab has been used to research breast cancer[1].

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

Tyk2-IN-9

Tyk2-IN-9 (Compound 26) is a selective Tyk-2 inhibitor with IC50s of 0.076 and 1.8 nM for TYK2-JH2 and JAK1-JH2, respectively. Tyk2-IN-9 can be used for the research of inflammatory or autoimmune disease[1].

  • CAS Number: 2694816-85-6
  • MF: C21H25N9O3
  • MW: 451.48
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PF-06747775

Mavelertinib is a selective, orally available and irreversible EGFR tyrosine kinase inhibitor (EGFR TKI), with IC50s of 5, 4, 12 and 3 nM for Del, L858R, and double mutants T790M/L858R and T790M/Del, respectively. Mavelertinib can be used for the research of non-small-cell lung cancer (NSCLC)[1][2][3][4].

  • CAS Number: 1776112-90-3
  • MF: C18H22FN9O2
  • MW: 415.425
  • Catalog: EGFR
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AG-494

AG-494 (Tyrphostin AG 494) is a potent and selective EGFR tyrosine kinase inhibitor (IC50=0.7 μM). AG-494 inhibits the autophosphorylation of EGFR, ErbB2, HER1-2 and PDGF-R with IC50s 1.1, 39, 45 and 6 μM, respectively. AG-494 blocks Cdk2 activation and inhibits EGF-dependent DNA synthesis[1][2][3].

  • CAS Number: 133550-35-3
  • MF: C16H12N2O3
  • MW: 280.278
  • Catalog: CDK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 586.9±50.0 °C at 760 mmHg
  • Melting Point: 249 °C(dec.)
  • Flash Point: 308.8±30.1 °C

SU5204

SU5204, a tyrosine kinase inhibitor extracted from patent US5792783A, has IC50s of 4 and 51.5 μM for FLK-1 (VEGFR-2) and HER2, respectively[1].

  • CAS Number: 186611-11-0
  • MF: C17H15NO2
  • MW: 265.30700
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

C188-9

C188-9 is a Stat3 inhibitor, with a Kd of 4.7 nM.

  • CAS Number: 432001-19-9
  • MF: C27H21NO5S
  • MW: 471.524
  • Catalog: STAT
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 680.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 365.6±34.3 °C

STAT3-IN-23

STAT3-IN-23 (PY*LKTK) is a potent STAT3 inhibitor[1].

  • CAS Number: 286465-26-7
  • MF: C36H61N8O12P
  • MW: 828.89
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BEBT-109 is a potent pan-mutant-selective EGFR inhibitor. BEBT-109 has improved pharmacokinetic properties. BEBT-109 can be used for multiple mutant-EGFR-driven non-small cell lung cancer (NSCLC) research[1].

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