Notch-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/Notch.html NotchNotch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notchsignaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on

2、ajuxtaposed cell.Regulation of Notch signaling is critical to development and maintenance of most eukaryotic organisms. The Notch receptors(NOTCH1, 2, 3, and 4) and ligands (DLL1, 3, and 4, JAG1 and 2) are integral membrane proteins and direct cell-cell interactions areneeded to activate signaling.

3、Ligand-expressing cells activate Notch signaling through an unusual mechanism involving Notchproteolysis to release the intracellular domain from the membrane, allowing the Notch receptor to function directly as thedownstream signal transducer.www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/Not

4、ch.html Notch HYPERLINK https:/www.MedChemE/Targets/Notch.html HYPERLINK https:/www.MedChemE/Targets/Notch.html Inhibitors, HYPERLINK https:/www.MedChemE/Targets/Notch.html HYPERLINK https:/www.MedChemE/Targets/Notch.html Activators HYPERLINK https:/www.MedChemE/Targets/Notch.html HYPERLINK https:/w

5、ww.MedChemE/Targets/Notch.html & HYPERLINK https:/www.MedChemE/Targets/Notch.html HYPERLINK https:/www.MedChemE/Targets/Notch.html Modulators HYPERLINK https:/www.MedChemE/asr-490.html ASR-490Cat. No.: HY-144899 HYPERLINK https:/www.MedChemE/BMS-708163.html Avagacestat(BMS-708163) Cat. No.: HY-50845

6、ASR-490 reduces the viability of HCT116 and SW620cells by downregulating Notch1 signaling. ASR-490overcomes Notch1 overexpression and inhibits thegrowth of HCT/Notch1 transfectants. ASR-490inhibits the tumor growth in control (pCMV/HCT116)and Notch1/HCT116 in xenotransplanted mice.Purity: 98%Clinica

7、l Data: No Development ReportedSize: 1 mg, 5 mgAvagacestat (BMS-708163) is a potent inhibitor of-secretase, with IC s of 0.27 nM and 0.30 nM50for A42 and A40 inhibition; Avagacestat(BMS-708163) also inhibits NICD (NotchIntraCellular Domain) with IC of 0.84 nM and50shows weak inhibition of CYP2C19, w

8、ith IC of50Purity: 98.28%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg HYPERLINK https:/www.MedChemE/bms-906024.html BMS-906024 HYPERLINK https:/www.MedChemE/bms-906024.html HYPERLINK https:/www.MedChemE/BMS-983970.html BMS-983970Cat. No.: HY-15670 Cat. No.: HY-12419BMS-906024 is an ora

9、lly active and selective-secretase (gamma secretase) inhibitor.BMS-906024 is a potent pan-Notch receptorsinhibitor with IC s of 1.6 nM, 0.7 nM, 3.4 nM,50and 2.9 nM for Notch1, -2, -3, and -4 receptors,respectively.BMS-983970 is an oral pan-Notch inhibitor for thetreatment of multiplecancers.Purity:

10、98.07%Clinical Data: Phase 1Size: 5 mg, 10 mg, 25 mgPurity: 99.42%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/bruceine-d.html Bruceine HYPERLINK https:/www.MedChemE/bruceine-d.html HYPERLINK https:/www.MedChemE/bruceine-d.html D HY

11、PERLINK https:/www.MedChemE/bruceine-d.html HYPERLINK https:/www.MedChemE/bt-gsi.html BT-GSICat. No.: HY-N3014 Cat. No.: HY-145428Bruceine D is a Notch inhibitor with anti-canceractivity and induces apoptosis in several humancancer cells. Bruceine D is an effective botanicalinsect antifeedant with o

12、utstanding systemicproperties, causing potent pest growth inhibitoryactivity.BT-GSI is a -secretase inhibitor (GSI) and abone-targeted Notch inhibitor. BT-GSI has dualanti-myeloma and anti-resorptive properties, whichcan be used for the research of multiple myelomaand associated bone disease. BT-GSI

13、 inhibits tumorgrowth and osteolytic disease progression.Purity: 95.75%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 20 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/carvacrol.html Carvacrol HYPERLINK https:/www.MedChemE/carv

14、acrol.html HYPERLINK https:/www.MedChemE/notch-in-2.html CB-103Cat. No.: HY-N0711 Cat. No.: HY-135145Carvacrol is a monoterpenoid phenol isolated fromLamiaceae family plants, with antioxidant,anti-inflammatory and anticancer properties.Carvacrol causes cell cycle arrest in G0/G1,downregulates Notch-

15、1, and Jagged-1, and inducesapoptosis.CB-103 is a first-in-class, orally activeprotein-protein interaction (PPI) inhibitor of theNOTCH transcriptional activation complex. CB-103has anti-tumor activity.Purity: 99.96%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 100 mgPurity: 99.77%Clinical

16、Data: Phase 2Size: 10 mM 1 mL, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/LY3039478.html Crenigacestat HYPERLINK https:/www.MedChemE/LY3039478.html HYPERLINK https:/www.MedChemE/DAPT.html DAPT(LY3039478) Cat. No.: HY-12449 (GSI-IX) Cat. No.: HY-13027Crenigacestat (LY3039478) is an orally act

17、iveNotch and -secretase inhibitor, with an IC of501 nM in most of the tumor cell lines tested.DAPT (GSI-IX) is a potent and orally active-secretase inhibitor with IC s of 115 nM and50200 nM for total amyloid- (A) and A ,42respectively. DAPT inhibits the activation ofNotch 1 signaling and induces cel

18、ldifferentiation.Purity: 98.33%Clinical Data: Phase 2Size: 10 mM 1 mL, 2 mg, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.93%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg2 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/FLI-06.html F

19、LI-06 HYPERLINK https:/www.MedChemE/FLI-06.html HYPERLINK https:/www.MedChemE/IMR-1.html IMR-1Cat. No.: HY-15860 Cat. No.: HY-100431FLI-06 is an inhibitor of Notch signaling with anEC of 2.3 M.50IMR-1 is a novel class of Notch inhibitortargeting the transcriptional activation with anIC of 26 M.50Pur

20、ity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.88%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/IMR-1A.html IMR-1A HYPERLINK https:/www.MedChemE/IMR-1A.html HYPERLINK https:/www

21、.MedChemE/jagged-1-188-204.html Jagged-1 HYPERLINK https:/www.MedChemE/jagged-1-188-204.html HYPERLINK https:/www.MedChemE/jagged-1-188-204.html (188-204)Cat. No.: HY-100431A Cat. No.: HY-P1846IMR-1A, a acid metabolite of IMR-1, is a Notchinhibitor with an IC of 0.5 M. IMR-1A has a5050-fold increase

22、 in potency with respect to IMR-1.IMR-1 can metabolize in vivo to IMR-1A.Jagged-1 (188-204) is a fragment of the Jagged-1(JAG-1) protein. JAG-1 is a Notch ligand highlyexpressed in cultured and primary multiple myeloma(MM) cells. JAG-1 induces maturation ofmonocyte-derived human dendritic cells.Puri

23、ty: 98.23%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/jagged-1-188-204-tfa.html Jagged-1 HYPERLINK https:/www.MedChemE/jagged-1-188-204-tfa.html HYPERLINK https:/www.MedChemE/jag

24、ged-1-188-204-tfa.html (188-204) HYPERLINK https:/www.MedChemE/jagged-1-188-204-tfa.html HYPERLINK https:/www.MedChemE/jagged-1-188-204-tfa.html (TFA) HYPERLINK https:/www.MedChemE/jagged-1-188-204-tfa.html HYPERLINK https:/www.MedChemE/JI051.html JI051Cat. No.: HY-P1846A Cat. No.: HY-117113Jagged-1

25、 (188-204) TFA is a fragment of theJagged-1 (JAG-1) protein. JAG-1 is a Notch ligandhighly expressed in cultured and primary multiplemyeloma (MM) cells. JAG-1 induces maturation ofmonocyte-derived human dendritic cells.JI051 is a stabilizer for the Hes1-PHB2interaction. JI051 interacts with acancer-

26、associated protein chaperone prohibitin 2(PHB2), induces cell-cycle arrest by inhibitingthe Notch downstream effector gene Hes1.Anti-cancer activity.Purity: 99.68%Clinical Data: No Development ReportedSize: 1 mg, 5 mg, 10 mgPurity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 1

27、0 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/ly-411575.html LY-411575 HYPERLINK https:/www.MedChemE/ly-411575.html HYPERLINK https:/www.MedChemE/notch-1-tfa.html Notch HYPERLINK https:/www.MedChemE/notch-1-tfa.html HYPERLINK https:/www.MedChemE/notch-1-tfa.html 1 HYPERLINK https:/www.MedChemE/n

28、otch-1-tfa.html HYPERLINK https:/www.MedChemE/notch-1-tfa.html TFACat. No.: HY-50752 Cat. No.: HY-P1985ALY-411575 is a potent -secretase inhibitor withIC of 0.078 nM/0.082 nM (membrane/cell-based),50and also inhibits Notch S3 cleavage with IC of500.39 nM.Notch 1 TFA (Notch homolog 1,translocation-as

29、sociated) can encode a member ofthe NOTCH family of proteins.Purity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/notch-inhibitor-1.html Notch HYPERLINK https:/ww

30、w.MedChemE/notch-inhibitor-1.html HYPERLINK https:/www.MedChemE/notch-inhibitor-1.html inhibitor HYPERLINK https:/www.MedChemE/notch-inhibitor-1.html HYPERLINK https:/www.MedChemE/notch-inhibitor-1.html 1 HYPERLINK https:/www.MedChemE/notch-inhibitor-1.html HYPERLINK https:/www.MedChemE/Psoralidin.h

31、tml PsoralidinCat. No.: HY-12860 Cat. No.: HY-N0232Notch inhibitor 1 is a potent Notch inhibitor,with IC s of 7.8 and 8.5 nM for Notch 1 and Notch503, respectively. Used in the research of cancer.Psoralidin is a dual inhibitor of COX-2 and5-LOX, regulates ionizing radiation (IR)-inducedpulmonary inf

32、lammation.Anti-cancer,anti-bacterial, and anti-inflammatory properties.Psoralidin significantly downregulates NOTCH1signaling.Purity: 99.81%Clinical Data: No Development ReportedSize: 5 mg, 10 mgPurity: 99.90%Clinical Data: No Development ReportedSize: 5 mg, 10 mgwww.MedChemE 3 HYPERLINK https:/www.

33、MedChemE/rbpj-inhibitor-1.html RBPJ HYPERLINK https:/www.MedChemE/rbpj-inhibitor-1.html HYPERLINK https:/www.MedChemE/rbpj-inhibitor-1.html Inhibitor-1(RIN1) Cat. No.: HY-137471 HYPERLINK https:/www.MedChemE/RO4929097.html RO4929097(RG-4733) Cat. No.: HY-11102RBPJ Inhibitor-1 (RIN1), the first RBPJi

34、nhibitor, blocks the functional interaction ofRBPJ with SHARP. RBPJ Inhibitor-1 (RIN1) inhibitsNOTCH-dependent tumor cell proliferation.RO4929097 (RG-4733) is a secretase inhibitorwith IC of 4 nM, inhibiting cellular processing50of A40 and Notch with EC of 14 nM and 5 nM,50respectively.Purity: 99.11

35、%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.11%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/rovalpituzumab.html Rovalpituzumab HYPERLINK https:/www.MedChemE/rovalpituzumab.html HYPERLINK http

36、s:/www.MedChemE/sahm1.html SAHM1Cat. No.: HY-P99043 Cat. No.: HY-P2203Rovalpituzumab is a humanized monoclonal antibodyagainst delta-like protein 3 (DLL3).Rovalpituzumab can be used in the synthesis ofantibody-drug conjugate (ADC), RovalpituzumabTesirine. Rovalpituzumab has activity againstsmall cel

37、l lung cancer (SCLC).SAHM1, a peptide mimetic of a dominant negativeform of mastermind-like (MAML), inhibits canonicalNotch transcription complex formation. SAHM1 canbe used for the research of allergic airwayinflammation in mice.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurit

38、y: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/sahm1-tfa.html SAHM1 HYPERLINK https:/www.MedChemE/sahm1-tfa.html HYPERLINK https:/www.MedChemE/sahm1-tfa.html TFACat. No.: HY-P2203A HYPERLINK https:/www.MedChemE/Semagacestat.html Semagacestat(LY450139) Cat.

39、 No.: HY-10009SAHM1 TFA is a Notch pathway inhibitor. SAHM1 TFAstabilizes hydrocarbon-stapled alpha helicalpeptide. SAHM1 TFA targets the protein-proteininterface and prevents Notch complex assembly.Semagacestat is a -secretase inhibitor, inhibits-amyloid (A42), A38 and A40 with IC s50of 10.9, 12 an

40、d 12.1 nM, respectively; alsoinhibits Notch signaling with IC of 14.1 nM.50Semagacestat can be used for the research ofalzheimers disease.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.56%Clinical Data: Phase 3Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:

41、/www.MedChemE/Tangeretin.html Tangeretin HYPERLINK https:/www.MedChemE/Tangeretin.html HYPERLINK https:/www.MedChemE/tCFA15.html tCFA15(Tangeritin; NSC53909; NSC618905) Cat. No.: HY-N0133Cat. No.: HY-104031Tangeretin (Tangeritin), a flavonoid from citrusfruit peels, has been proven to play an import

42、antrole in anti-inflammatory responses andneuroprotective effects in several disease models,and is a Notch-1 inhibitor.tCFA15 is a trimethyl cyclohexenonic long chainfatty alcohol containing 15 carbon atoms on theside chain, promotes the differentiation ofneurons, and may regulates Notch signaling.P

43、urity: 99.51%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.37%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/valproic-acid.html Valproic HYPERLINK https:/www.MedChemE/valproic-acid.html H

44、YPERLINK https:/www.MedChemE/valproic-acid.html acid HYPERLINK https:/www.MedChemE/valproic-acid.html HYPERLINK https:/www.MedChemE/Valproic-acid-sodium-salt.html Valproic HYPERLINK https:/www.MedChemE/Valproic-acid-sodium-salt.html HYPERLINK https:/www.MedChemE/Valproic-acid-sodium-salt.html acid H

45、YPERLINK https:/www.MedChemE/Valproic-acid-sodium-salt.html HYPERLINK https:/www.MedChemE/Valproic-acid-sodium-salt.html sodium(VPA; 2-Propylpentanoic Acid) Cat. No.: HY-10585 (Sodium Valproate sodium) Cat. No.: HY-10585AValproic acid (VPA; 2-Propylpentanoic Acid) is anHDAC inhibitor, with IC in the

46、 range of 0.5 and502 mM, also inhibits HDAC1 (IC , 400 M), and50induces proteasomal degradation of HDAC2.Valproic acid sodium salt (Sodium Valproate) is anHDAC inhibitor, with IC in the range of 0.5 and502 mM, also inhibits HDAC1 (IC , 400 M), and50induces proteasomal degradation of HDAC2.Purity: 98

47、.0%Clinical Data: LaunchedSize: 500 mg, 1 g, 5 g, 25 gPurity: 98.0%Clinical Data: LaunchedSize: 500 mg, 1 g, 5 g, 25 g4 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/valproic-acid-d14-sodium.html Valproic HYPERLINK https:/www.MedChemE/valproic-acid-d14-sodium

48、.html HYPERLINK https:/www.MedChemE/valproic-acid-d14-sodium.html acid-d14 HYPERLINK https:/www.MedChemE/valproic-acid-d14-sodium.html HYPERLINK https:/www.MedChemE/valproic-acid-d14-sodium.html sodium(Sodium Valproate-d14 sodium) Cat. No.: HY-10585AS1 HYPERLINK https:/www.MedChemE/valproic-acid-d15

49、.html Valproic HYPERLINK https:/www.MedChemE/valproic-acid-d15.html HYPERLINK https:/www.MedChemE/valproic-acid-d15.html acid-d15(VPA-d15; 2-Propylpentanoic Acid-d15) Cat. No.: HY-10585S2Valproic acid-d14 (sodium) is deuterium labeledValproic acid (sodium). Valproic acid sodium salt(Sodium Valproate

50、) is an HDAC inhibitor, with IC50in the range of 0.5 and 2 mM, also inhibits HDAC1(IC50, 400 M), and induces proteasomaldegradation of HDAC2.Valproic acid-d15 is the deuterium labeledValproic acid. Valproic acid (VPA;2-Propylpentanoic Acid) is an HDAC inhibitor,with IC in the range of 0.5 and 2 mM,

51、also50inhibits HDAC1 (IC , 400 M), and induces50proteasomal degradation of HDAC2.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/valproic-acid-d4.html Valproic HYPERLINK https:/www.MedChe

52、mE/valproic-acid-d4.html HYPERLINK https:/www.MedChemE/valproic-acid-d4.html acid-d4(VPA-d4; 2-Propylpentanoic Acid-d4) Cat. No.: HY-10585S HYPERLINK https:/www.MedChemE/valproic-acid-d4-sodium.html Valproic HYPERLINK https:/www.MedChemE/valproic-acid-d4-sodium.html HYPERLINK https:/www.MedChemE/val

53、proic-acid-d4-sodium.html acid-d4 HYPERLINK https:/www.MedChemE/valproic-acid-d4-sodium.html HYPERLINK https:/www.MedChemE/valproic-acid-d4-sodium.html sodium(VPA-d4 sodium; 2-Propylpentanoic Acid-d4 sodium) Cat. No.: HY-10585S3Valproic acid-d4 (VPA-d4) is the deuterium labeledValproic acid. Valproi

54、c acid (VPA;2-Propylpentanoic Acid) is an HDAC inhibitor,with IC in the range of 0.5 and 2 mM, also50inhibits HDAC1 (IC , 400 M), and induces50proteasomal degradation of HDAC2.Valproic acid-d4 (VPA-d4) sodium is the deuteriumlabeled Valproic acid. Valproic acid (VPA;2-Propylpentanoic Acid) is an HDA

55、C inhibitor,with IC in the range of 0.5 and 2 mM, also50inhibits HDAC1 (IC , 400 M), and induces50proteasomal degradation of HDAC2.Purity: 98%Clinical Data: No Development ReportedSize: 1 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/2-propyl-2-2-d

56、2-pentanoic-4-4-d2-acid.html Valproic HYPERLINK https:/www.MedChemE/2-propyl-2-2-d2-pentanoic-4-4-d2-acid.html HYPERLINK https:/www.MedChemE/2-propyl-2-2-d2-pentanoic-4-4-d2-acid.html acid-d4-1(VPA-d4-1; 2-Propylpentanoic Acid-d4-1) Cat. No.: HY-10585S4 HYPERLINK https:/www.MedChemE/valproic-acid-d6

57、.html Valproic HYPERLINK https:/www.MedChemE/valproic-acid-d6.html HYPERLINK https:/www.MedChemE/valproic-acid-d6.html acid-d6(VPA-d6; 2-Propylpentanoic Acid-d6) Cat. No.: HY-10585S1Valproic acid-d4-1 (VPA-d4-1) is the deuteriumlabeled Valproic acid. Valproic acid (VPA;2-Propylpentanoic Acid) is an

58、HDAC inhibitor,with IC in the range of 0.5 and 2 mM, also50inhibits HDAC1 (IC , 400 M), and induces50proteasomal degradation of HDAC2.Valproic acid-d6 (VPA-d6) is the deuterium labeledValproic acid. Valproic acid (VPA;2-Propylpentanoic Acid) is an HDAC inhibitor,with IC in the range of 0.5 and 2 mM,

59、 also50inhibits HDAC1 (IC , 400 M), and induces50proteasomal degradation of HDAC2.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.71%Clinical Data: No Development ReportedSize: 5 mg, 10 mg HYPERLINK https:/www.MedChemE/5-hydroxy-valproic-acid-d7-sodium-salt.html Valproic HYPERLINK https:/www.MedChemE/5-hydroxy-valproic-acid-d7-sodium-salt.html HYPE