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 >
Arenavirus Bacterial CMV Enterovirus Filovirus Fungal HBV HCV HIV HSV Influenza Virus Parasite Reverse Transcriptase RSV SARS-CoV
Antibody-drug Conjugate >
ADC Cytotoxin ADC Linker Drug-Linker Conjugates for ADC PROTAC-linker Conjugate for PAC
Apoptosis >
Apoptosis Bcl-2 Family c-Myc Caspase DAPK Ferroptosis IAP MDM-2/p53 PKD RIP kinase Survivin Thymidylate Synthase TNF Receptor
Autophagy >
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Antifolate APC ATM/ATR Aurora Kinase Casein Kinase CDK Checkpoint Kinase (Chk) CRISPR/Cas9 Deubiquitinase DNA Alkylator/Crosslinker DNA-PK DNA/RNA Synthesis Eukaryotic Initiation Factor (eIF) G-quadruplex Haspin Kinase HDAC HSP IRE1 Kinesin LIM Kinase (LIMK) Microtubule/Tubulin Mps1 Nucleoside Antimetabolite/Analog p97 PAK PARP PERK Polo-like Kinase (PLK) PPAR RAD51 ROCK Sirtuin SRPK Telomerase TOPK Topoisomerase Wee1
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Immunology/Inflammation >
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JAK/STAT Signaling >
EGFR JAK Pim STAT
MAPK/ERK Pathway >
ERK JNK KLF MAP3K MAP4K MAPKAPK2 (MK2) MEK Mixed Lineage Kinase MNK p38 MAPK Raf Ribosomal S6 Kinase (RSK)
Membrane Transporter/Ion Channel >
ATP Synthase BCRP Calcium Channel CFTR Chloride Channel CRAC Channel CRM1 EAAT2 GABA Receptor GlyT HCN Channel iGluR Monoamine Transporter Monocarboxylate Transporter Na+/Ca2+ Exchanger Na+/HCO3- Cotransporter Na+/K+ ATPase nAChR NKCC P-glycoprotein P2X Receptor Potassium Channel Proton Pump SGLT Sodium Channel TRP Channel URAT1
Metabolic Enzyme/Protease >
15-PGDH 5 alpha Reductase 5-Lipoxygenase Acetyl-CoA Carboxylase Acyltransferase Adenosine Deaminase Adenosine Kinase Aldehyde Dehydrogenase (ALDH) Aldose Reductase Aminopeptidase Angiotensin-converting Enzyme (ACE) ATGL ATP Citrate Lyase Carbonic Anhydrase Carboxypeptidase Cathepsin CETP COMT Cytochrome P450 Dipeptidyl Peptidase Dopamine β-hydroxylase E1/E2/E3 Enzyme Elastase Enolase FAAH FABP Factor Xa Farnesyl Transferase Fatty Acid Synthase (FAS) FXR Glucokinase GSNOR Gutathione S-transferase HCV Protease Hexokinase HIF/HIF Prolyl-Hydroxylase HIV Integrase HIV Protease HMG-CoA Reductase (HMGCR) HSP Indoleamine 2,3-Dioxygenase (IDO) Isocitrate Dehydrogenase (IDH) Lactate Dehydrogenase LXR MAGL Mineralocorticoid Receptor Mitochondrial Metabolism MMP Nampt NEDD8-activating Enzyme Neprilysin PAI-1 PDHK PGC-1α Phosphatase Phosphodiesterase (PDE) Phospholipase Procollagen C Proteinase Proteasome Pyruvate Kinase RAR/RXR Renin ROR Ser/Thr Protease SGK Stearoyl-CoA Desaturase (SCD) Thrombin Tryptophan Hydroxylase Tyrosinase Xanthine Oxidase
Neuronal Signaling >
5-HT Receptor AChE Adenosine Kinase Amyloid-β Beta-secretase CaMK CGRP Receptor COMT Dopamine Receptor Dopamine Transporter FAAH GABA Receptor GlyT iGluR Imidazoline Receptor mAChR Melatonin Receptor Monoamine Oxidase nAChR Neurokinin Receptor Opioid Receptor Serotonin Transporter γ-secretase
NF-κB >
NF-κB IKK Keap1-Nrf2 MALT1
PI3K/Akt/mTOR >
Akt AMPK ATM/ATR DNA-PK GSK-3 MELK mTOR PDK-1 PI3K PI4K PIKfyve PTEN
PROTAC >
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Protein Tyrosine Kinase/RTK >
Ack1 ALK Bcr-Abl BMX Kinase Btk c-Fms c-Kit c-Met/HGFR Discoidin Domain Receptor DYRK EGFR Ephrin Receptor FAK FGFR FLT3 IGF-1R Insulin Receptor IRAK Itk PDGFR PKA Pyk2 ROS Src Syk TAM Receptor Trk Receptor VEGFR
Stem Cell/Wnt >
Casein Kinase ERK Gli GSK-3 Hedgehog Hippo (MST) JAK Notch Oct3/4 PKA Porcupine ROCK sFRP-1 Smo STAT TGF-beta/Smad Wnt YAP β-catenin γ-secretase
TGF-beta/Smad >
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Vitamin D Related >
VD/VDR
Others >
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EGFR-IN-76

EGFR-IN-76 (compound 37A) is a potent inhibitor of EGFR[1].

  • CAS Number: 2607829-38-7
  • MF: C30H30ClFN6O2
  • MW: 561.05
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

GSK2646264

GSK2646264 (Compound 44) is a potent and selective spleen tyrosine kinase (SYK) inhibitor with a pIC50 of 7.1. GSK2646264 also inhibits other kinases with pIC50 values of 5.4, 5.4, 5.3, 5, 4.5, <4.6 and <4.3 against LCK, LRRK2, GSK3β, JAK2, VEGFR2, Aurora B and Aurora A, respectively. GSK2646264 is penetrable into the epidermis and dermis of the skin[1].

  • CAS Number: 1398695-47-0
  • MF: C24H26N2O2
  • MW: 374.48
  • Catalog: LRRK2
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 517.4±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 266.7±30.1 °C

JCN037

JCN037 (JGK037) is non-covalent and BBB-penetrant EGFR tyrosine kinase inhibitor, with IC50 values of 2.49 nM, 3.95 nM, 4.48 nM for EGFR, p-wtEGFR and pEGFRvⅢ, respectively[1].

  • CAS Number: 2305154-31-6
  • MF: C16H11BrFN3O2
  • MW: 376.18
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-16

EGFR-IN-16 (compound 3) is a potent EGFR inhibitor with pIC50 of 4.85 and 4.74 for EGFR and HER-2, respectively[1].

  • CAS Number: 133550-22-8
  • MF: C16H11NO3
  • MW: 265.26
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY 456236

LY456236 is a selective, non-competitive and orally active mGlu1 receptor antagonist that inhibits phosphoinositide hydrolysis with an IC50 of 0.145 μM. LY456236 also inhibits EGFR with an IC50 of 0.91 μM[1][3].

  • CAS Number: 338736-46-2
  • MF: C16H16ClN3O2
  • MW: 317.770
  • Catalog: mGluR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

pp60 (v-SRC) Autophosphorylation Site, Phosphorylated

pp60 (v-SRC) Autophosphorylation Site, Phosphorylated is the phosphorylated peptide of an EGFR substrate. pp60 (v-SRC) Autophosphorylation Site, Phosphorylated can be used for the screening of EGFR Kinase inhibitors via phosphorylated-substrate quantification[1].

  • CAS Number: 176042-83-4
  • MF: C66H110N23O26P
  • MW: 1672.70
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TUL01101

TUL01101 is a potent, selective and orally active JAK1 inhibitor, with an IC50s of 3, 37, 1517 and 36 nM for JAK1, JAK2, JAK3, and TYK2, respectively. TUL01101 can be used for the research of rheumatoid arthritis[1].

  • CAS Number: 2411222-97-2
  • MF: C22H25F2N5O2
  • MW: 429.46
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-9 dihydrochloride

H-9 Dihydrochloride is a PKA (protein kinase) inhibitor. H-9 Dihydrochloride (10 μM) significantly reduces the excitatory response to 5-HT. H-9 Dihydrochloride also has a direct effect on pharyngeal activity. H-9 Dihydrochloride inhibits signal-transduction and cell growth in EGF (epidermal growth factor)-dependent epithelial cell lines[1][2][3].

  • CAS Number: 116700-36-8
  • MF: C11H15Cl2N3O2S
  • MW: 324.227
  • Catalog: 5-HT Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: 250-255ºC dec.
  • Flash Point: N/A

Barecetamab

Barecetamab (ISU-104) is a fully human anti-ErbB3 monoclonal antibody. Barecetamab can be used for the research of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)[1].

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

PIM1-IN-7

PIM1-IN-7 (compound 6c) is a potent PIM-1 inhibitor, with an IC50 of 0.67 μM. PIM1-IN-7 shows the high cytotoxicity activity against HCT-116 and MCF-7 cells, with IC50 values of 42.9 and 7.68 μM, respectively[1].

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

Abrocitinib

Abrocitinib (PF-04965842) is a potent, oral active and selective JAK1 inhibitor, with IC50s of 29 and 803 nM for JAK1 and JAK2, respectively. Abrocitinib (PF-04965842) exhibits less active effect on TYK2 (IC50, 1.253 μM), and inhibits phosphorylation of STAT1,STAT3 and STAT5 after stimulation. Effective in autoimmune disease[1].

  • CAS Number: 1622902-68-4
  • MF: C14H21N5O2S
  • MW: 323.415
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-28

JAK-IN-28 (Compound 111) is a JAK inhibitor. JAK-IN-28 can be used for research of cancer or inflammatory diseases[1].

  • CAS Number: 2445500-22-9
  • MF: C20H18ClN7O
  • MW: 407.86
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Befotertinib

Befotertinib (D-0316) is the third-generation EGFR tyrosine kinase inhibitor. Befotertinib can be used for the research of EGFR T790M-positive non-small cell lung cancer (NSCLC)[1].

  • CAS Number: 1835667-63-4
  • MF: C29H32F3N7O2
  • MW: 567.61
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Intetumumab

Intetumumab (CNTO 95) is a potent anti-EGFR monoclonal antibody that is glycoengineered for enhanced antibody-dependent cellular cytotoxicity (ADCC). Intetumumab can be used in research of cancer[1][2].

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

JAK-IN-21

JAK-IN-21 (Example 4) is a selective and potent JAK inhibitor with IC50s of 1.73, 2.04, 109 and 62.9 nM against JAK1, JAK2, J2V617F and TYK2, respectively[1].

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

EGFR-IN-85

EGFR-IN-85 (Compound 1) is an EGFR inhibitor. EGFR-IN-85 has IC50 value of 0.19 μM for EGFRvⅢ phosphorylation. EGFR-IN-85 can suppress EGFR signaling within tumors. EGFR-IN-85 can be used for Glioblastoma (GBM) research[1].

  • CAS Number: 1956378-29-2
  • MF: C26H30N8O2
  • MW: 486.57
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TX2-121-1

TX2-121-1 is a bivalent hydrophobically tagged adamantane derivative of TX1-85-1, a potent, selective, ATP-competitive Her3 (ErbB3) inhibitor; induces degradation and interferences with Her2/Her3 and c-Met/Her3 interactions, prevents Her3 heterodimerization, induces preferential death of Her3-dependent cell lines with an EC50 in the range of 0.8-1.4 uM.

  • CAS Number: 1603845-42-6
  • MF: C42H52N8O3
  • MW: 716.931
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

4,8-Dimethoxy-1-vinyl-9H-β-carboline

Dehydrocrenatidine, a natural alkaloid, is a specific JAK inhibitor. Dehydrocrenatidine inhibits voltage-gated sodium channels and ameliorates mechanic allodia in a rat model of neuropathic pain[1][2].

  • CAS Number: 65236-62-6
  • MF: C15H14N2O2
  • MW: 254.284
  • Catalog: Apoptosis
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 491.8±40.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 174.9±17.6 °C

HTH-01-091

HTH-01-091 is a potent and selective, cell-permeable, ATP-competitive MELK inhibitor with biochemical IC50 of 10.5 nM; displays no significant activity for PIK3CA, mTOR, GSK3A and CDK7 (IC50>600 nM); exhibits substantially improved kinome selectivity in comparison with OTSSP167; induces MELK degradation, but demonstrates poor antiproliferative effects in basal-like breast cancer cell lines.

  • CAS Number: 2000209-42-5
  • MF: C26H28Cl2N4O2
  • MW: 499.436
  • Catalog: RIP kinase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SJ988497

SJ988497 is a PROTAC JAK2 degrader. SJ988497 potently inhibits CRLF2-rearranged (CRLF2r) cell proliferation and degrades the CRBN neosubstrate GSPT1. SJ988497 consists of a Ruxolitinib (HY-50856) derivative, linker, and CRBN ligand Pomalidomide. SJ988497 can be used in the research of acute lymphoblastic leukemia (ALL)[1].

  • CAS Number: 2595365-41-4
  • MF: C36H36N10O5
  • MW: 688.74
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3-IN-12

JAK3-IN-12 (compound 15k) is a highly potent JAK3 inhibitor with an IC50 value of 9.5 nM. JAK3-IN-12 can be used for researching rheumatoid arthritis[1].

  • CAS Number: 1430095-86-5
  • MF: C19H19N5O4S
  • MW: 413.45
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

BD750

BD750, an effective immunosuppressant and a JAK3/STAT5 inhibitor, inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation, with IC50 values of 1.5 μM and 1.1 μM in mouse and human T cells, respectively[1][2].

  • CAS Number: 892686-59-8
  • MF: C14H13N3OS
  • MW: 271.34
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK-IN-24

JAK-IN-24 is a JAK inhibitor, with IC50s of 0.534 and 24 nM at the presence of 4 μM or 1mM ATP, respectively. JAK-IN-24 also inhibits PBMC IL-15 induced STAT5 phosphorylation with an IC50 of 86.171 nM[1].

  • CAS Number: 2042629-43-4
  • MF: C20H25N5O2
  • MW: 367.44
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gefitinib-d3

Gefitinib-d3 (ZD1839-d3) is the deuterium labeled Gefitinib. Gefitinib (ZD1839) is a potent, selective and orally active EGFR tyrosine kinase inhibitor with an IC50 of 33 nM. Gefitinib selectively inhibits EGF-stimulated tumor cell growth (IC50 of 54 nM) and that blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Gefitinib also induces autophagy. Gefitinib has antitumour activity[1][2].

  • CAS Number: 1173976-40-3
  • MF: C22H21ClD3FN4O3
  • MW: 449.92100
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tyrphostin 51

Tyrphostin A51 is a potent protein tyrosine kinase (PTK) inhibitor. Tyrphostin A51 inhibits the volume-dependent release of [3H]taurine in a dose-dependent manner. Tyrphostin A51 markedly reduces cellular tyrosyl phosphorylation level. Tyrphostin A51 inhibits both basal and EGF-induced human bone cell proliferation[1][2].

  • CAS Number: 126433-07-6
  • MF: C13H8N4O3
  • MW: 268.228
  • Catalog: EGFR
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 788.2±60.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 430.5±32.9 °C

Afatinib (BIBW2992)

(E/Z)-Afatinib ((E/Z)-BIBW 2992) is the mixture of (E)-Afatinib and (Z)-Afatinib. Afatinib (HY-10261) is an irreversible inhibitor of EGFR, by irreversibly binding to their ATP binding site to block activation of EGFR, HER2, HER4, and EGFRvIII. Afatinib used in co-administration with Temozolomide (HY-17364), potently targeting to EGFRvIII-cMet signaling in glioblastoma cells[1].

  • CAS Number: 439081-18-2
  • MF: C24H25ClFN5O3
  • MW: 485.94
  • Catalog: Apoptosis
  • 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

SIAIS164018

SIAIS164018 is a PROTAC-based ALK and EGFR degrader, which is designed from Brigatinib, with IC50 value of 2.5 nM and 6.6 nM for ALK and ALK G1202R, respectively. SIAIS164018 strongly inhibits cancer cells migration and invasion, causes G1 cell cycle arrest and induces apoptosis. SIAIS164018 exhibits better property than Brigatinib[1].

  • CAS Number: 2353492-68-7
  • MF: C43H48ClN10O7P
  • MW: 883.33
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ruxolitinib (INCB018424)

Ruxolitinib is a potent and selective JAK1/2 inhibitor with IC50s of 3.3 nM and 2.8 nM in cell-free assays, and has 130-fold selectivity for JAK1/2 over JAK3.

  • CAS Number: 941678-49-5
  • MF: C17H18N6
  • MW: 306.365
  • Catalog: Autophagy
  • Density: 1.4±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

(R)-Afatinib

(R)-Afatinib ((R)-BIBW 2992) is the Afatinib isomer. Afatinib (HY-10261) 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 can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer[1].

  • CAS Number: 439081-17-1
  • MF: C24H25ClFN5O3
  • MW: 485.9384032
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Losatuxizumab

Losatuxizumab (ABT-806) is an anti-EGFR monoclonal antibody. Losatuxizumab binds to EGFR with EC50s of 0.96 nM for EGFR wild-type, 0.09 nM for EGFRC271A,C283A, 0.12 nM for EGFRvIII, 0.66 nM for EGFR1-501. Losatuxizumab can be used for research of EGFR-expressing cancers[1][2].

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