1、 HYPERLINK https:/www.MedChemE/Targets/IRE1.html IRE1Inositol requiring enzyme 1Inositol-requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of theunfolded protein response (UPR) during endoplasmic reticulum (ER) stress. It represents a p

2、otential therapeutic target for a numberof diseases associated with endoplasmic reticulum stress.IRE1 is the only identified ER stress sensor in yeast and essential for UPR in animals and plants. As an ER transmembrane protein,IRE1 monitors ER homeostasis through an ER luminal stress-sensing domain

3、and triggers UPR through a cytoplasmic kinase domainand an RNase domain. Upon ER stress, IRE1 RNase is activated through conformational change, autophosphorylation, and higherorder oligomerization. Mammalian IRE1 initiates diverse downstream signaling of the UPR either through unconventional splicin

4、gof the transcription factor Xbp-1 or and through posttranscriptional modifications via Regulated IRE1-Dependent Decay (RIDD) ofmultiple substrates.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/IRE1.html IRE1 HYPERLINK https:/www.MedChemE/Targets/IRE1.html HYPERLINK https:/www.MedChemE/Target

5、s/IRE1.html Inhibitors HYPERLINK https:/www.MedChemE/Targets/IRE1.html HYPERLINK https:/www.MedChemE/Targets/IRE1.html & HYPERLINK https:/www.MedChemE/Targets/IRE1.html HYPERLINK https:/www.MedChemE/Targets/IRE1.html Antagonists HYPERLINK https:/www.MedChemE/3,6-DMAD_hydrochloride.html 3,6-DMAD HYPE

6、RLINK https:/www.MedChemE/3,6-DMAD_hydrochloride.html HYPERLINK https:/www.MedChemE/3,6-DMAD_hydrochloride.html hydrochlorideCat. No.: HY-U00460 HYPERLINK https:/www.MedChemE/4_mu_8C.html 48C(IRE1 Inhibitor III) Cat. No.: HY-197073,6-DMAD hydrochloride is a inhibitor of theIRE1-XBP1 pathway of the u

7、nfolded proteinresponse.48C (IRE1 Inhibitor III) is a small-moleculeinhibitor of IRE1.Purity: 98.88%Clinical Data: No Development ReportedSize: 5 mgPurity: 98.78%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/NSC95682.html 6-Br

8、omo-2-hydroxy-3-methoxybenzaldehyde(NSC95682) Cat. No.: HY-107371 HYPERLINK https:/www.MedChemE/APY29.html APY29Cat. No.: HY-175376-Bromo-2-hydroxy-3-methoxybenzaldehyde (NSC95682)is an IRE-1 inhibitor with an IC of 0.08 M,50extracted from patent WO 2008154484 A1, IRE-linhibitor compound 3-5.APY29,

9、an ATP-competitive inhibitor, is anallosteric modulator of IRE1 which inhibits IRE1autophosphorylation by binding to the ATP-bindingpocket with IC of 280 nM. APY29 acts as a ligand50that allosterically activates IRE1 adjacent RNasedomain.Purity: 99.55%Clinical Data: No Development ReportedSize: 10 m

10、M 1 mL, 50 mgPurity: 99.90%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10 mg, 50 mg HYPERLINK https:/www.MedChemE/B_I09.html B HYPERLINK https:/www.MedChemE/B_I09.html HYPERLINK https:/www.MedChemE/B_I09.html I09 HYPERLINK https:/www.MedChemE/B_I09.html HYPERLINK https:/www.MedChemE/GSK2

11、850163.html GSK2850163Cat. No.: HY-107400 Cat. No.: HY-U00459B I09 is an IRE-1 RNase inhibitor, with an IC of501230 nM.GSK2850163 is a novel inhibitor ofinositol-requiring enzyme-1 alpha (IRE1) which caninhibit IRE1 kinase activity and RNase activitywith IC s of 20 and 200 nM, respectively.50Purity:

12、 99.60%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.48%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg HYPERLINK https:/www.MedChemE/GSK2850163_hydrochloride.html GSK2850163 HYPERLINK https:/www.MedChemE/GSK2850163_hydrochlor

13、ide.html HYPERLINK https:/www.MedChemE/GSK2850163_hydrochloride.html hydrochloride HYPERLINK https:/www.MedChemE/GSK2850163_hydrochloride.html HYPERLINK https:/www.MedChemE/ire1-kinase-in-1.html IRE1 HYPERLINK https:/www.MedChemE/ire1-kinase-in-1.html HYPERLINK https:/www.MedChemE/ire1-kinase-in-1.h

14、tml kinase-IN-1Cat. No.: HY-U00459B Cat. No.: HY-136735GSK2850163 hydrochloride is a novel inhibitor ofinositol-requiring enzyme-1 alpha (IRE1) which caninhibit IRE1 kinase activity and RNase activitywith IC s of 20 and 200 nM, respectively.50IRE1 kinase-IN-1 is a highly selective IRE1(ERN1) inhibit

15、or, with an IC of 77 nM. IRE150kinase-IN-1 displays 100-fold selectivity forIRE1 over the IRE1 isoform.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.44%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/ire1-kinas

16、e-in-2.html IRE1 HYPERLINK https:/www.MedChemE/ire1-kinase-in-2.html HYPERLINK https:/www.MedChemE/ire1-kinase-in-2.html kinase-IN-2 HYPERLINK https:/www.MedChemE/ire1-kinase-in-2.html HYPERLINK https:/www.MedChemE/ire1-kinase-in-6.html IRE1 HYPERLINK https:/www.MedChemE/ire1-kinase-in-6.html HYPERL

17、INK https:/www.MedChemE/ire1-kinase-in-6.html kinase-IN-6Cat. No.: HY-18509 Cat. No.: HY-142659IRE1 kinase-IN-2 is a potent IRE1 kinaseinhibitor, with an EC of 0.82 M. IRE150kinase-IN-2 inhibits IRE1 kinaseautophosphorylation (IC =3.12 M). IRE150kinase-IN-2 inhibits XBP1 mRNA splicing in the WTcell

18、lines.IRE1 kinase-IN-6 is a potent IRE1 inhibitor withan IC value of 4.4 nM.50Purity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg2 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK

19、https:/www.MedChemE/ixa4.html IXA4 HYPERLINK https:/www.MedChemE/ixa4.html HYPERLINK https:/www.MedChemE/kira-7.html KIRA-7Cat. No.: HY-139214 Cat. No.: HY-124646IXA4 is a highly selective, non-toxic IRE1/XBP1sactivator. IXA4 activates IRE1/XBP1s signalingwithout globally activating the unfolded pro

20、teinresponse (UPR) or other stress-responsivesignaling pathways (e.g., the heat shock responseor oxidative stress response).KIRA-7, an imidazopyrazine compound, binds theIRE1 kinase (IC of 110 nM) to allosterically50inhibit its RNase activity. KIRA-7 has ananti-fibrotic effect.Purity: 99.16%Clinical

21、 Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/KIRA6.html KIRA6Cat. No.: HY-19708 HYPERLINK https:/www.MedChemE/Kira8.html Kira8(AMG-18) Cat. No.: HY-114368KIR

22、A6 is an advanced small-molecule IRE1 RNasekinase inhibitor with an IC of 0.6 M. KIRA6 can50trigger an apoptotic response.Kira8 (AMG-18) is a mono-selective IRE1 inhibitorthat allosterically attenuates IRE1 RNase activitywith an IC of 5.9 nM.50Purity: 99.86%Clinical Data: No Development ReportedSize

23、: 5 mg, 10 mg, 25 mg, 50 mgPurity: 99.74%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/kira8-hydrochloride.html Kira8 HYPERLINK https:/www.MedChemE/kira8-hydrochloride.html HYPERLINK https:/www.MedChemE/kira8-hydrochloride.html Hydro

24、chloride(AMG-18 Hydrochloride) Cat. No.: HY-114368A HYPERLINK https:/www.MedChemE/kira9.html KIRA9Cat. No.: HY-145422Kira8 Hydrochloride (AMG-18 Hydrochloride) is amono-selective IRE1 inhibitor that allostericallyattenuates IRE1 RNase activity with an IC of 5.950nM.KIRA9 is a potent IRE1 inhibitor (

25、IC =4.8 M in50INS-1 cells). KIRA9 is able to fully engage theATP-binding site of IRE1. KIRA9 can blockER-localized mRNA decay and apoptosis.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE

26、/MKC3946.html MKC3946 HYPERLINK https:/www.MedChemE/MKC3946.html HYPERLINK https:/www.MedChemE/IRE-1_alpha_inhibitor_1.html MKC8866Cat. No.: HY-19710 Cat. No.: HY-104040MKC3946 is a potent IRE1 inhibitor, used forcancer research.MKC8866, a salicylaldehyde analog, is a potent,selective IRE1 RNase inh

27、ibitor with an IC of500.29M in human vitro.Purity: 99.68%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.87%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/MKC9989.html MKC9989

28、HYPERLINK https:/www.MedChemE/MKC9989.html HYPERLINK https:/www.MedChemE/pair2.html PAIR2Cat. No.: HY-12399 Cat. No.: HY-145425MKC9989 is a Hydroxy aryl aldehydes (HAA)inhibitor and also inhibits IRE1 with an IC of500.23 to 44 M.PAIR2 is a potent and selective partial antagonistof IRE1 RNase. PAIR2

29、can completely occupyIRE1s ATP-binding site in cells and block theability of a potent KIRA to inhibit XBP1 splicing.Purity: 98.36%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgwww.MedChemE 3 HY

30、PERLINK https:/www.MedChemE/STF-083010.html STF-083010Cat. No.: HY-15845 HYPERLINK https:/www.MedChemE/Sunitinib.html Sunitinib(SU 11248) Cat. No.: HY-10255ASTF-083010 is a specific IRE1 inhibitor.STF-083010 inhibits Ire1 endonuclease activity,without affecting its kinase activity, afterendoplasmic

31、reticulum stress.Sunitinib (SU 11248) is a multi-targeted receptortyrosine kinase inhibitor with IC s of 80 nM and502 nM for VEGFR2 and PDGFR, respectively.Purity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg, 200 mgPurity: 98.96%Clinical Data: LaunchedSize

32、: 10 mM 1 mL, 100 mg, 200 mg, 500 mg HYPERLINK https:/www.MedChemE/Sunitinib-Malate.html Sunitinib HYPERLINK https:/www.MedChemE/Sunitinib-Malate.html HYPERLINK https:/www.MedChemE/Sunitinib-Malate.html Malate(SU 11248 Malate) Cat. No.: HY-10255 HYPERLINK https:/www.MedChemE/sunitinib-d10.html Sunitinib-d10(SU 11248-d10) Cat. No.: HY-10255ASSunitinib Malate (SU 11248 Malate) is amulti-targeted receptor tyrosine kinase inhibitorwith IC50s of 80 nM and 2 nM for VEGFR2 andPDGFR, respectively.Sunitinib D10 (SU 11248 D10) is a