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.


Anti-infection >
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Neratinib (HKI-272)

Neratinib is an orally available, irreversible tyrosine kinase inhibitor with IC50s of 59 nM and 92 nM for HER2 and EGFR, respectively.

  • CAS Number: 698387-09-6
  • MF: C30H29ClN6O3
  • MW: 557.043
  • Catalog: EGFR
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 757.0±60.0 °C at 760 mmHg
  • Melting Point: 184 °C
  • Flash Point: 411.6±32.9 °C

PD-161570

PD-161570 is a potent and ATP-competitive human FGF-1 receptor inhibitor with an IC50 of 39.9 nM and a Ki of 42 nM. PD-161570 also inhibits the PDGFR, EGFR and c-Src tyrosine kinases with IC50 values of 310 nM, 240 nM, and 44 nM, respectively. PD-161570 inhibits PDGF-stimulated autophosphorylation and FGF-1 receptor phosphorylation with IC50s of 450 nM and 622 nM, respectively[1][2]. PD-161570 is also a bone morphogenetic proteins (BMPs) and TGF-β signaling inhibitor[3].

  • CAS Number: 192705-80-9
  • MF: C26H35Cl2N7O
  • MW: 532.50800
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 157 °C
  • Flash Point: N/A

PP3

PP 3 (Compound 3) is an EGFR tyrosine kinase inhibitor with an IC50 of 2.7 μM[1].

  • CAS Number: 5334-30-5
  • MF: C11H9N5
  • MW: 211.223
  • Catalog: EGFR
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 364.0±35.0 °C at 760 mmHg
  • Melting Point: 214-217 °C
  • Flash Point: 173.9±25.9 °C

WP1066

WP1066 is an inhibitor of JAK2 and STAT3, and also shows effect on STAT5 and ERK1/2, without affecting JAK1 and JAK3.

  • CAS Number: 857064-38-1
  • MF: C17H14BrN3O
  • MW: 356.217
  • Catalog: JAK
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 569.9±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 298.5±30.1 °C

Ponezumab

Ponezumab (PF-04360365) is a humanised anti-amyloid IgG2 monoclonal antibody. Ponezumab reduces Aβ levels in the central nervous system and improves performance in mice in various models of learning and memory. Ponezumab can be used in study of Alzheimer's disease[1].

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

Trastuzumab

Trastuzumab (PBS) is a humanized IgG1 monoclonal antibody for patients with invasive breast cancers that overexpress HER2. Trastuzumab (PBS) has the potential for HER2 Positive Metastatic Breast Cancer and HER2 Positive Gastric Cancer research.

  • CAS Number: 180288-69-1
  • MF: C6470H10012N1726O2013S42
  • MW: 145531.50
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

afatinib

Afatinib (BIBW 2992) is an irreversible EGFR family inhibitor with IC50s of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively.

  • CAS Number: 850140-72-6
  • MF: C24H25ClFN5O3
  • MW: 485.938
  • Catalog: Autophagy
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 676.9±55.0 °C at 760 mmHg
  • Melting Point: 100 - 102 °C
  • Flash Point: 363.2±31.5 °C

EGFR-IN-71

EGFR-IN-71 is a potent narrow spectrum epidermal growth factor receptor (EGFR) inhibitor with IC50 values of 3.7 μM. EGFR-IN-71 can be used for researching chordoma[1].

  • CAS Number: 2676155-98-7
  • MF: C16H9ClIN3
  • MW: 405.62
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Panitumumab

Panitumumab (ABX-EGF) is a fully human IgG2 anti-EGFR monoclonal antibody. Panitumumab has an anti-tumor activity[1].

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

AZD1480

AZD-1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of < 0.4 nM, selectively against JAK3 and Tyk2, and to a smaller extent against JAK1.

  • CAS Number: 935666-88-9
  • MF: C14H14ClFN8
  • MW: 348.766
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: 575.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 301.7±32.9 °C

SC-99

A novel selective STAT3 inhibitor that inhibits JAK2-STAT3 activation but has no effects on other transcription factors such as NF-κB, and kinases such as AKT, ERK, and c-Src; inhibits STAT3 phosphorylation, dimerization and nuclear translocation, downregulates STAT3-modulated gene expression and induces MM cell apoptosis; delays tumor growth in MM xenograft models (30mg/kg); orally active.

  • CAS Number: 882290-02-0
  • MF: C15H8Cl2FN3O
  • MW: 336.147
  • Catalog: Apoptosis
  • Density: 1.38±0.1 g/cm3(Predicted)
  • Boiling Point: 459.4±55.0 °C(Predicted)
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-6

JAK3/BTK-IN-6 (compound 14h) is a potent BTK and JAK3 dual inhibitor, with IC50 values of 0.6 and 0.4 nM, respectively. JAK3/BTK-IN-6 shows good metabolic stability in human liver microsome. JAK3/BTK-IN-6 can be used for hematological and immune diseases research[1].

  • CAS Number: 2243136-03-8
  • MF: C21H17BF3N5O3
  • MW: 455.20
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Desmethyl dosimertinib-d5

N-Desmethyl dosimertinib-d5 is the deuterium labeled Dosimertinib (HY-142283). Dosimertinib is a highly potent, selective, and orally active deuterated EGFR inhibiotor. Dosimertinib can be used for the research of non-small-cell lung cancer[1][2].

  • CAS Number: 2719691-00-4
  • MF: C27H26D5N7O2
  • MW: 490.61
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-64

EGFR-IN-64 (Compound 3c) is a potent EGFR inhibitor with an IC50 of 0.33 μM. EGFR-IN-64 shows anticancer activity[1].

  • CAS Number: 2416924-93-9
  • MF: C20H21N3O3
  • MW: 351.40
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

XZH-5

XZH-5 is a small moelcule that inhibits constitutive and interleukin-6-induced STAT3 phosphorylation, inhibits STAT3 DNA binding ability and downregulation of STAT3 downstream genes; inhibits downregulation of STAT3 downstream genes, such as Bcl-2, Bcl-xL, Cyclin D1 and Survivin, demonstrates blockade of STAT3 phosphorylation in human rhabdomyosarcoma cells with apoptosis and suppresses colony-forming ability and cell migration; blocks IL-6-induced STAT3 phosphorylation and nuclear translocation but not the stimulation of STAT1 phosphorylation by IFN-γ.

  • CAS Number: 1360562-98-6
  • MF: C22H25F6N5O4
  • MW: 537.463
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PROTAC STAT3 degrader-2

PROTAC STAT3 degrader-2 is a selective and efficacious PROTAC degrader of STAT3 protein with a DC50 of 3.54 μM in Molm-16 Cell. PROTAC STAT3 degrader-2 has the potential for cancer research[1].

  • CAS Number: 2429877-78-9
  • MF: C59H60F2N9O13P
  • MW: 1172.13
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SYK/JAK-IN-1

SYK/JAK-IN-1 is dual SYK/JAK inhibitor with IC50s of <5 nM for SYK and JAK2, respectively[1].

  • CAS Number: 2737326-28-0
  • MF: C24H26N8O3
  • MW: 474.52
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AS2863619

AS2863619 enables conversion of antigen-specific effector/memory T cells into Foxp3+ regulatory T (Treg) cells for the treatment of various immunological diseases. AS2863619 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 inhibition of CDK8/19, which consequently activates the Foxp3 gene[1].

  • CAS Number: 2241300-51-4
  • MF: C16H14Cl2N8O
  • MW: 405.24
  • Catalog: CDK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pan-HER-IN-2

pan-HER-IN-2 (Compound C6) is a reversible, orally active pan-HER inhibitor with IC50 values of 0.72, 2.0, 8.2 and 75.1 nM against EGFR, HER4, EGFRT790M/L858R and HER2, respectively. pan-HER-IN-2 induces apoptosis and shows antitumor activities[1].

  • CAS Number: 1639040-95-1
  • MF: C19H15BrClN5O
  • MW: 444.71
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

HER2-IN-7

HER2-IN-7 is a potent inhibitor of HER2. Deregulation of ErbB family signalling modulates proliferation, invasion, metastasis, angiogenesis, and tumour cell survival. HER2-IN-7 has the potential for the research of diseases associated ErbBs (especially HER2), including cancer (extracted from patent WO2019214634A1, compound 23)[1].

  • CAS Number: 2387574-01-6
  • MF: C28H26F3N7O3
  • MW: 565.55
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

CEP-1347

CEP-1347 is an inhibitor of the JNK/SAPK pathway with neuroprotective effects.

  • CAS Number: 156177-65-0
  • MF: C33H33N3O5S2
  • MW: 615.76200
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pan-HER-IN-1

pan-HER-IN-1 (Compound C5) is an irreversible, orally active pan-HER inhibitor with IC50 values of 0.38, 1.6, 2.2 and 3.5 nM against EGFR, HER4, EGFRT790M/L858R and HER2, respectively. pan-HER-IN-1 induces apoptosis and shows antitumor activities[1].

  • CAS Number: 1639040-94-0
  • MF: C19H14BrN5O
  • MW: 408.25
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Povorcitinib phosphate

Povorcitinib phosphate is a potent and selective inhibitor of JAK1. Povorcitinib phosphate has the potential for the research of disease selected from cutaneous lupus erythematosus (CLE) and Lichen planus (LP)[1].

  • CAS Number: 1637677-33-8
  • MF: C23H25F5N7O5P
  • MW: 605.45
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GLPG0634

GLPG0634 is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively.

  • CAS Number: 1206161-97-8
  • MF: C21H23N5O3S
  • MW: 425.504
  • Catalog: JAK
  • Density: 1.5±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Laprituximab emtansine

Laprituximab emtansine (IMGN-289) is an immunotoxin targeting HER1. Laprituximab emtansine is an EGFR antibody-drug conjugate (ADC) consisting of the J2898A antibody, DM1 (anti-microtubule agent) and the SMCC thioether linker. Laprituximab emtansine can be used for cancer research[1][2][3].

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

TCS PIM-1 1

TCS PIM-1 1(sc-204330) is a potent and selective ATP-competitive Pim-1 kianse inhibitor with IC50 of 50 nM, displays good selectivity over Pim-2 and MEK1/MEK2(IC50s >20,000 nM).IC50 value: 50 nM [1]Target: Pim-1TCS PIM-1 1 bound convincingly within the ATP-binding site of Pim-1 suggesting an ATP-competitive inhibitory mechanism. Preliminary data further suggested that 1 lacked in vitro inhibitory activity toward related serine/threonine kinases Pim-2 and MEK1/2 (IC50 > 20 lM). Hence, small molecules similar to TCS PIM-1 1 may serve as useful starting scaffolds for the development of other improved yet selective Pim-1 inhibitors.

  • CAS Number: 491871-58-0
  • MF: C18H11BrN2O2
  • MW: 367.196
  • Catalog: Pim
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 592.6±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 312.2±30.1 °C

Yuanhuadin

Yuanhuadin, extracted from Genkwa Flos Daphne genkwa, has antitumor activity through inhibiting Akt/mTOR and EGFR pathways, induce cell-cycle arrest and abortion[1].

  • CAS Number: 76402-66-9
  • MF: C32H42O10
  • MW: 586.67000
  • Catalog: EGFR
  • Density: 1.34g/cm3
  • Boiling Point: 704.4ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 222.4ºC

Lapatinib ditosylate hydrate

Lapatinib ditosylate monohydrate (GW572016 ditosylate monohydrate) 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: 388082-78-8
  • MF: C86H86Cl2F2N8O21S6
  • MW: 943.476
  • Catalog: Autophagy
  • Density: 1.403 g/mL (20.84 °C)
  • Boiling Point: 750.7ºC at 760 mmHg
  • Melting Point: 237 - 239 °C
  • Flash Point: 68 °F

AC-4-130

AC-4-130 is a novel, potent STAT5 SH2 domain inhibitor, binds to and efficiently blocks STAT5 activation and subsequent transcriptional activity, shows high selectivity for STAT5 over STAT1 and STAT3; disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription; substantially impairs the proliferation and clonogenic growth of human AML cell lines and primary FLT3-ITD+ AML patient cells in vitro and in vivo; synergistically increases the cytotoxicity of the JAK1/2 inhibitor Ruxolitinib and the p300/pCAF inhibitor Garcinol in vivo.

  • CAS Number: 1834571-82-2
  • MF: C37H36ClF5N2O5S
  • MW: 751.206
  • Catalog: STAT
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Laprituximab

Laprituximab (J2898A) is a humanized IgG1 anti-EGFR antibody that can be used for the synthesis of ADC IMGN289[1].

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