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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EAI001

EAI001 is a potent, selective mutant epidermal growth factor receptor (EGFR) allosteric inhibitor with an IC50 value of 24 nM for EGFRL858R/T790M. EAI001 can be used for research of cancer[1][2].

  • CAS Number: 892772-75-7
  • MF: C19H15N3O2S
  • MW: 349.41
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Afatinib impurity 11

Afatinib impurity 11 is an impurity of Afatinib. Afatinib 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[1].

  • CAS Number: 1402086-20-7
  • MF: C21H18ClFN4O3
  • MW: 428.84
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gefitinib-based PROTAC 3

Gefitinib-based PROTAC 3, conjugating an EGFR binding element to a VHL ligand via a linker, induces EGFR degradation with DC50s of 11.7 nM and 22.3 nM in HCC827(exon 19 del) and H3255 (L858R mutantion) cells, respectively[1].

  • CAS Number: 2230821-27-7
  • MF: C47H57ClFN7O8S
  • MW: 934.51
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(R)-Lisofylline

(R)-Lisofylline ((R)-Lisophylline) is a (R)-enantiomer of the metabolite of Pentoxifylline with anti-inflammatory properties. (R)-Lisofylline is a lysophosphatidic acid acyltransferase inhibitor with an IC50 of 0.6 µM and interrupts IL-12 signaling-mediated STAT4 activation. (R)-Lisofylline has the potential for type 1 diabetes, autoimmune disorders research[1][2].

  • CAS Number: 100324-81-0
  • MF: C13H20N4O3
  • MW: 280.323
  • Catalog: STAT
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 511.2±56.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 263.0±31.8 °C

Gefitinib N-oxide

Gefitinib N-oxide is the N-oxide derivative of Gefitinib. Gefitinib is an EGFR tyrosine kinase inhibitor, with IC50 of 2-37 nM in NR6wtEGFR cells[1][2].

  • CAS Number: 847949-51-3
  • MF: C22H24ClFN4O4
  • MW: 462.90200
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-1

JAK3/BTK-IN-1 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-1 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147952A1, compound 002)[1].

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

EGFR-IN-21

EGFR-IN-21 is a potent EGFR inhibtior with an IC50 of 0.38 nM. EGFR-IN-21 has antitumor activity[1].

  • CAS Number: 2648206-31-7
  • MF: C36H44BrN10O2P
  • MW: 759.68
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Theliatinib (HMPL-309)

Theliatinib (HMPL-309) is a potent, ATP-competitive and highly selective EGFR inhibitor, significantly inhibits phosphorylation of EGFR (p-EGFR) and its downstream targets, AKT and ERK (p-AKT and p-ERK), with anti-tumor activity. Theliatinib (HMPL-309) shows a Ki of 0.05 nM for wild type EGFR, and IC50s of 3 and 22 nM for EGFR and EGFR T790M/L858R mutant, respectively[1].

  • CAS Number: 1353644-70-8
  • MF: C25H26N6O2
  • MW: 442.52
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Tubulin/JAK2-IN-1

Tubulin/JAK2-IN-1 (compound 7g) is a dual inhibitor of Janus kinase 2 (JAK2) and microtubule. Tubulin/JAK2-IN-1 has potent antiproliferative activity against the cancer cells[1].

  • CAS Number: 2933938-46-4
  • MF: C22H20N6O3
  • MW: 416.43
  • Catalog: Microtubule/Tubulin
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Margetuximab

Margetuximab (MGAH22) is a chimeric anti-HER2 monoclonal antibody optimized Fc domain, with an EC50 value of 39.33 ng/mL. Margetuximab can be used for researching metastatic HER2-positive breast cancer[1].

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

CDK6/PIM1-IN-1

CDK6/PIM1-IN-1 is a potent and balanced dual CDK6/PIM1 inhibitor with IC50 values of 39 and 88 nM, respectively. CDK6/PIM1-IN-1 inhibits CDK4 (IC50=3.6 nM). CDK6/PIM1-IN-1 significantly inhibits acute myeloid leukemia (AML) cell proliferation, arrest cell cycle at the G1 phase, and promote cell apoptosis. CDK6/PIM1-IN-1 exhibits potent anti-AML activity[1].

  • CAS Number: 2677026-14-9
  • MF: C25H28FN9
  • MW: 473.55
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TK4b

TK4b is a Janus kinase (JAK) inhibitor with the IC50 values of 19.40 nM and 18.42 nM for JAK2 and JAK3, respectively. TK4b can be used in lymphoid-derived diseases and leukemia cancer research[1].

  • CAS Number: 2232890-81-0
  • MF: C21H22N2O2
  • MW: 334.41
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DBPR112

DBPR112 (compound 78) is an orally active Furanopyrimidine-Based Epidermal Growth Factor Receptor inhibitor with IC50s of 15 nM and 48 nM for EGFRWT and EGFRL858R/T790M, respectively. DBPR112 has significant antitumor efficacy[1].

  • CAS Number: 1226549-49-0
  • MF: C32H31N5O3
  • MW: 533.62
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR-IN-82

EGFR-IN-82 (Cmpound 8a) is a potent and orally active EGFR inhibitor with IC50 values of 0.09 and 0.06 nM for EGFRL858R/T790M/C797S and EGFRDel19/T790M/C797S, respectively. EGFR-IN-82 has no significant effect on EGFRWT. EGFR-IN-82 has anti-proliferative activity and inhibits tumor formation in nude mice. EGFR-IN-82 can be used in non-small cell lung cancer research [1].

  • CAS Number: 2568086-81-5
  • MF: C32H41BrN9O2P
  • MW: 694.60
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Erlotinib-d6 (hydrochloride)

Erlotinib D6 hydrochloride (CP-358774 D6 hydrochloride) a deuterium labeled Erlotinib Hydrochloride. Erlotinib Hydrochloride inhibits purified EGFR kinase with an 50 of 2 nM[1].

  • CAS Number: 1189953-78-3
  • MF: C22H18D6ClN3O4
  • MW: 435.93400
  • Catalog: Autophagy
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pelitinib-d6

Pelitinib-d6 (EKB-569-d6) is the deuterium labeled Pelitinib. Pelitinib (EKB-569) is an irreversible inhibitor of EGFR with an IC50 of 38.5 nM; also slightly inhibits Src, MEK/ERK and ErbB2 with IC50s of 282, 800, and 1255 nM, respectively[1][2].

  • CAS Number: 1325223-34-4
  • MF: C24H17D6ClFN5O2
  • MW: 473.96
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Varlitinib tosylate

Varlitinib (ASLAN001) tosylate is a potent, reversible, small molecule pan-EGFR inhibitor with IC50s of 7, 2, 4 nM for HER1, HER2 and HER4, respectively[1].

  • CAS Number: 1146629-86-8
  • MF: C36H35ClN6O8S3
  • MW: 811.35
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

EGFR/HER2/TS-IN-1

EGFR/HER2/TS-IN-1 (Compound 4d) is an EGFR, HER2 and TS (Thymidylate synthase) inhibitor with IC50 values of 0.203, 0.088 and 0.168 μM against EGFR, HER2 and TS, respectively. EGFR/HER2/TS-IN-1 induces MCF7 cell apoptosis[1].

  • CAS Number: 2444363-11-3
  • MF: C24H15N5O4S2
  • MW: 501.54
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

JAK3/BTK-IN-2

JAK3/BTK-IN-2 is a potent inhibitor of JAK3/BTK. BTK and JAK3 are two important targets for autoimmune diseases. Simultaneous inhibition of the BTK/JAK3 signalling pathway exhibits synergistic effects. JAK3/BTK-IN-2 has the potential for the research of JAK3 kinase and/or BTK-related diseases (extracted from patent WO2021147952A1, compound 004)[1]

  • CAS Number: 2674036-93-0
  • MF: C25H32N8O2
  • MW: 476.57
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-Methyl-dosimertinib-d5

N-Methyl-dosimertinib-d5 is the deuterium labeled of 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: 2719690-98-7
  • MF: C24H19D5N6O2
  • MW: 433.52
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Fedratinib hydrochloride hydrate

Fedratinib hydrochloride hydrate (TG-101348 hydrochloride hydrate) is a potent, selective, ATP-competitive and orally active JAK2 inhibitor with IC50s of 3 nM for both JAK2 and JAK2V617F kinase. Fedratinib hydrochloride hydrate shows 35- and 334-fold selectivity over JAK1 and JAK3, respectively. Fedratinib hydrochloride hydrate induces cancer cell apoptosis and has the potential for myeloproliferative disorders research[1][2].

  • CAS Number: 1374744-69-0
  • MF: C27H40Cl2N6O4S
  • MW: 615.615
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

N-(1,1-Dimethylethyl)-3-[[5-methyl-2-[[3-(4-morpholinylmethy-l)phenyl]amino]-4-pyrimidinyl]amino]benz

JAK-IN-32 (XC) is a bi-aryl meta-pyrimidine inhibitor of JAK kinase[1].

  • CAS Number: 936091-56-4
  • MF: C26H34N6O3S
  • MW: 510.65
  • Catalog: JAK
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 686.9±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 369.3±34.3 °C

Pimozide-d4

Pimozide D4 (R6238 D4) is a deuterium labeled Pimozide. Pimozide is a dopamine receptor antagonist, with Kis of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a Ki of 39 nM; Pimozide also inhibits STAT3 and STAT5[1][2][3].

  • CAS Number: 1803193-57-8
  • MF: C28H25D4F2N3O
  • MW: 465.57
  • Catalog: Adrenergic Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TYK2 JH2-IN-1-d3

TYK2?JH2-IN-1-d3 is the a deuterated, orally active and selective TYK2 inhibitor (compound 4h), targeting to JH2 domain (IC50=0.1 nM)[1].

  • CAS Number: 2376999-19-6
  • MF: C24H21D3FN9O3
  • MW: 508.52
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AZ7550-d5

AZ7550-d5 is the deuterium labeled AZ7550 (HY-B0794). AZ7550, an active metabolite of AZD9291 (HY-15772), inhibits the activity of IGF1R with an IC50 of 1.6 μM[1][2].

  • CAS Number: 2719690-99-8
  • MF: C27H26D5N7O2
  • MW: 490.61
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Osimertinib-13C,d3

Osimertinib-13C,d3 is the deuterium and 13C labeled Osimertinib. Osimertinib (AZD9291) is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M, respectively.

  • CAS Number: 2254100-49-5
  • MF: C2713CH30D3N7O2
  • MW: 503.62
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

NSC689857

NSC689857 is a potent EGFR and SCFSKP2 inhibitor with an IC50 value of 36 μM for Skp2-Cks1. NSC689857 can inhibit p27 ubiquitylation (IC50=30 μM). NSC689857 has varied activity across cancer types, with more activity against leukemia cell lines than others[1][2].

  • CAS Number: 241127-79-7
  • MF: C25H29NO4
  • MW: 407.50
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

DZD1516

DZD1516 is a potent and selective HER2 inhibitor (IC50=0.56 nM) with good blood-brain permeability. DZD1516 exhibits antitumor activity in CNS and subcutaneous xenograft mouse models[1].

  • CAS Number: 2387570-00-3
  • MF: C28H27F2N7O3
  • MW: 547.56
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

PDE5-IN-3

PDE5-IN-3 (compound 11j) is a potent PDE5 inhibitor with an IC50 of 1.57 nM. PDE5-IN-3 shows moderate EGFR inhibition with IC50 of 5.827 µM. PDE5-IN-3 significantly inhibits the Wnt/β-catenin pathway (IC50=1286.96 ng/mL). PDE5-IN-3 induces the intrinsic apoptotic mitochondrial pathway in HepG2 cells. PDE5-IN-3 has strong antitumor activity[1].

  • CAS Number: 2538149-57-2
  • MF: C21H14BrN5O2
  • MW: 448.27
  • Catalog: Apoptosis
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TX1-85-1

TX1-85-1 is a Her3 (ErbB3) inhibitor with an IC50 of 23 nM. TX1-85-1 induces partial degradation of Her3 protein and attenuates Her3-dependent signaling[1].

  • CAS Number: 1603845-32-4
  • MF: C32H36N8O3
  • MW: 580.679999999999
  • Catalog: EGFR
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A