γ-secretase-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/-secretase.html -secretaseGamma secretase-Secretase is a multimeric aspartyl protease that cleaves the membrane-spanning region of the -carboxyl terminal fragment(CTF) generated from -amyloid precursor protein. -Secretase defines the generated molecular species

2、 of amyloid -protein (A),a critical molecule in the pathogenesis of Alzheimers disease (AD).-Secretase is composed of four subunits: Aph-1, nicastrin (Nct), Pen-2 and presenilin (PS), which is the catalytic subunit of theenzyme. Endoproteolysis of PS, which results in the formation of PS1-NTF (N-ter

3、minal fragment) and CTF (C-terminal fragment)heterodimer, is required for -secretase activation. -Secretase cleaves amyloid precursor protein (APP), Notch and many othersubstrates. Aberrant cleavage of APP contributes to the pathogenesis of AD and abnormal Notch signaling promotes tumorgrowth. -Secr

4、etase is a highly valued drug target in Alzheimers disease and cancer. Multiple classes of small molecules that target-secretase have been developed, including both inhibitors (GSIs) and modulators (GSMs).www.MedChemE 1 HYPERLINK https:/www.MedChemE/Targets/-secretase.html -secretase HYPERLINK https

5、:/www.MedChemE/Targets/-secretase.html HYPERLINK https:/www.MedChemE/Targets/-secretase.html Inhibitors HYPERLINK https:/www.MedChemE/Targets/-secretase.html HYPERLINK https:/www.MedChemE/Targets/-secretase.html & HYPERLINK https:/www.MedChemE/Targets/-secretase.html HYPERLINK https:/www.MedChemE/Ta

6、rgets/-secretase.html Modulators HYPERLINK https:/www.MedChemE/3-5-bis-4-nitrophenoxy-benzoic-acid.html 3,5-Bis(4-nitrophenoxy)benzoic HYPERLINK https:/www.MedChemE/3-5-bis-4-nitrophenoxy-benzoic-acid.html HYPERLINK https:/www.MedChemE/3-5-bis-4-nitrophenoxy-benzoic-acid.html acidCat. No.: HY-103539

7、 HYPERLINK https:/www.MedChemE/BMS-708163.html Avagacestat(BMS-708163) Cat. No.: HY-508453,5-Bis(4-nitrophenoxy)benzoic acid is aninhibitor of -secretase.3,5-Bis(4-nitrophenoxy)benzoic acid causes adecrease in the released levels of A42 andnotch-1 A-like peptide 25 (N25).Purity: 98%Clinical Data: No

8、 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, with IC of5

9、0Purity: 98.28%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg HYPERLINK https:/www.MedChemE/a-beta-42-in-1.html A42-IN-1 HYPERLINK https:/www.MedChemE/a-beta-42-in-1.html HYPERLINK https:/www.MedChemE/a42-in-1-free-base.html A42-IN-1 HYPERLINK https:/www.MedChemE/a42-in-1-free-base.html

10、HYPERLINK https:/www.MedChemE/a42-in-1-free-base.html free HYPERLINK https:/www.MedChemE/a42-in-1-free-base.html HYPERLINK https:/www.MedChemE/a42-in-1-free-base.html baseCat. No.: HY-130609 Cat. No.: HY-130609AA42-IN-1, compound 1v, is a novel, potent andorally active -secretase modulator (GSM).A42

11、-IN-1 potently reduced A42 levels with anIC value of 0.091M without CYP3A450inhibition. A42-IN-1 shows a sustainedpharmacokinetic profile.A42-IN-1 free base (compound 1v) is an orallyactive, high brain exposure -secretasemodulator. A42-IN-1 free base potently reducesA42 levels with an IC value of 0.

12、091 M, and50significantly reduces brain A42 levels in mice.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/a42-in-2.html A42-IN-2Cat. No.: HY-136866 HYPERLINK https:/www.MedChemE/Begacest

13、at.html Begacestat(GSI-953) Cat. No.: HY-14175A42-IN-2 is a -secretase modulator extractedfrom patent WO2016070107, compound example 36.A42-IN-2 has an IC of 6.5 nM for .50 42A42-IN-2 can be used for the research ofAlzheimers disease.Begacestat (GSI-953) is a selective thiophenesulfonamide inhibitor

14、 of amyloid precursor proteingamma-secretase (IC A =15 nM) for the50 40treatment of Alzheimers disease.Purity: 98.14%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 50 mg, 100 mgPurity: 99.56%Clinical Data: Phase 1Size: 10 mM 1 mL, 1 mg HYPERLINK https:/www.MedChemE/BI-1408.html BI-140

15、8 HYPERLINK https:/www.MedChemE/BI-1408.html HYPERLINK https:/www.MedChemE/BMS-299897.html BMS HYPERLINK https:/www.MedChemE/BMS-299897.html HYPERLINK https:/www.MedChemE/BMS-299897.html 299897Cat. No.: HY-112282 Cat. No.: HY-50883BI-1408 is a potent secretase modulator withan IC50 of 0.04 M for A42

16、.BMS 299897 is a sulfonamide -secretase inhibitorwith an IC of 7 nM for A production inhibition50in HEK293 cells stably overexpressing amyloidprecursor protein (APP).Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.24%Clinical Data: No Development ReportedSize: 10 mM 1 mL,

17、 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/BMS_433796.html BMS HYPERLINK https:/www.MedChemE/BMS_433796.html HYPERLINK https:/www.MedChemE/BMS_433796.html 433796 HYPERLINK https:/www.MedChemE/BMS_433796.html HYPERLINK https:/www.MedChemE/bms-906024.html BMS-906024Cat. No.: HY-5

18、0884 Cat. No.: HY-15670BMS 433796 is a -secretase inhibitor with Alowering activity in a transgenic mouse model ofAlzheimers disease.BMS-906024 is an orally 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

19、 nM,50and 2.9 nM for Notch1, -2, -3, and -4 receptors,respectively.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.07%Clinical Data: Phase 1Size: 5 mg, 10 mg, 25 mg2 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/bpn-15606.html BPN-

20、15606 HYPERLINK https:/www.MedChemE/bpn-15606.html HYPERLINK https:/www.MedChemE/bpn-15606-besylate.html BPN-15606 HYPERLINK https:/www.MedChemE/bpn-15606-besylate.html HYPERLINK https:/www.MedChemE/bpn-15606-besylate.html besylateCat. No.: HY-117482 Cat. No.: HY-117482ABPN-15606 is a highly potent,

21、 orally active-secretase modulator (GSM), attenuates theproduction of A42 and A40 by SHSY5Yneuroblastoma cells with IC values of 7 nM and5017nM, respectively.BPN-15606 besylate is a highly potent, orallyactive -secretase modulator (GSM), attenuatesthe production of A42 and A40 by SHSY5Yneuroblastoma

22、 cells with IC values of 7 nM and5017nM, respectively.Purity: 99.24%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/bt-gsi.html BT-GSICat. No.: HY-145428 HYPERLINK https:

23、/www.MedChemE/Compound_E.html Compound HYPERLINK https:/www.MedChemE/Compound_E.html HYPERLINK https:/www.MedChemE/Compound_E.html E(-Secretase-IN-1) Cat. No.: HY-14176BT-GSI is a -secretase inhibitor (GSI) and abone-targeted Notch inhibitor. BT-GSI has dualanti-myeloma and anti-resorptive propertie

24、s, whichcan be used for the research of multiple myelomaand associated bone disease. BT-GSI inhibits tumorgrowth and osteolytic disease progression.Compound E is a -secretase inhibitor. Compound Ebloks -amyloid(40), -amyloid(42), and Notch-secretase cleavage with IC s of 0.24, 0.37,500.32 nM, respec

25、tively.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.91%Clinical Data: No Development ReportedSize: 1 mg, 5 mg, 10 mg, 25 mg HYPERLINK https:/www.MedChemE/LY3039478.html Crenigacestat(LY3039478) Cat. No.: HY-12449 HYPERLINK https:/www.MedChemE/DAPT.html DAPT(GSI-IX) Cat

26、. No.: HY-13027Crenigacestat (LY3039478) is an orally activeNotch 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 in

27、hibits the activation ofNotch 1 signaling and induces celldifferentiation.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 mg HYPERLINK https:/www.MedChemE/E-2012.html E

28、HYPERLINK https:/www.MedChemE/E-2012.html HYPERLINK https:/www.MedChemE/E-2012.html 2012 HYPERLINK https:/www.MedChemE/E-2012.html HYPERLINK https:/www.MedChemE/eln-318463.html ELN318463Cat. No.: HY-10016 Cat. No.: HY-50882E 2012 is a potent gamma () secretasemodulator without affecting Notch proces

29、sing. E2012 inhibits 3-hydroxysterol 24-reductase(DHCR24) at the final step in the cholesterolbiosynthesis.ELN318463 is an amyloid precursor protein (APP)selective -secretase inhibitor. ELN318463 showsdifferential inhibition of presenilin (PS1)- andPS2-comprised -secretase with EC s of 12 nM50and 65

30、6 nM for PS1 and PS2, respectively.ELN318463 is 51-fold more selective for PS1.Purity: 97.39%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 100 mgPurity: 99.33%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/ELN_318463_(racem

31、ate).html ELN318463 HYPERLINK https:/www.MedChemE/ELN_318463_(racemate).html HYPERLINK https:/www.MedChemE/ELN_318463_(racemate).html racemate HYPERLINK https:/www.MedChemE/ELN_318463_(racemate).html HYPERLINK https:/www.MedChemE/fosciclopirox.html FosciclopiroxCat. No.: HY-50882A(CPX-POM) Cat. No.:

32、 HY-109174ELN318463 racemate is the racemate of ELN318463.ELN318463 is an amyloid precursor protein (APP)selective -secretase inhibitor. ELN318463 showsdifferential inhibition of presenilin (PS1)- andPS2-comprised -secretase with EC s of 12nM and50656 nM for PS1and PS2, respectively.Fosciclopirox su

33、ppresses growth of urothelialcancer by targeting the -secretase complex.Fosciclopirox selectively delivers the activemetabolite, Ciclopirox (CPX), to the entireurinary tract. Ciclopirox has anticancer activityin a number of solid and hematologic malignancies.Purity: 98%Clinical Data: No Development

34、ReportedSize: 1 mg, 5 mgPurity: 99.73%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mgwww.MedChemE 3 HYPERLINK https:/www.MedChemE/frm-024.html FRM-024 HYPERLINK https:/www.MedChemE/frm-024.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1.html gamma-secreta

35、se HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1.html modulator HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1.html 1Cat. No.: HY-115726 Cat. No.: HY-1

36、0043FRM-024 is a potent CNS-penetrant gammasecretase modulator for familial Alzheimersdisease.-secretase inhibitior-1 is a gamma-secretasemodulator, -secretase inhibitior-1 is useful forAlzheimers disease.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98.0%Clinical Data: No

37、 Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1-hydrochloride.html gamma-secretase HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1-hydrochloride.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1-hydrochlori

38、de.html modulator HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1-hydrochloride.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1-hydrochloride.html 1 HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1-hydrochloride.html HYPERLINK https:/www.MedChemE/gamma-secretase-mod

39、ulator-1-hydrochloride.html hydrochloride HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-1-hydrochloride.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-2.html gamma-secretase HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-2.html HYPERLINK https:/www.MedChemE/gamma-sec

40、retase-modulator-2.html modulator HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-2.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-2.html 2Cat. No.: HY-10043A Cat. No.: HY-50754gamma-secretase inhibitior-1 is agamma-secretase modulator, -secretaseinhibitior-1 is useful for Alzh

41、eimers disease.gamma-secretase modulator 2 is a potent andselective -secretase modulator for treatment ofAlzheimers disease.Purity: 98.59%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.59%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10

42、mg, 50 mg HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-3.html gamma-secretase HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-3.html HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-3.html modulator HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-3.html HYPERLINK ht

43、tps:/www.MedChemE/gamma-secretase-modulator-3.html 3 HYPERLINK https:/www.MedChemE/gamma-secretase-modulator-3.html HYPERLINK https:/www.MedChemE/gsm-1.html GSM-1Cat. No.: HY-50889 Cat. No.: HY-119165gamma-secretase modulator 3 is a gamma-secretasemodulator.GSM-1 is a potent -secretase modulator. GS

44、M-1directly targets the transmembrane domain (TMD) 1of presenilin 1 (PS1).Purity: 99.35%Clinical Data: No Development ReportedSize: 10 mg, 100 mgPurity: 98.42%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/CHF5074.html Itanapraced HYPERLIN

45、K https:/www.MedChemE/CHF5074.html HYPERLINK https:/www.MedChemE/L-685458.html L-685458(CHF5074; CSP-1103) Cat. No.: HY-14399 (L-685,458) Cat. No.: HY-19369Itanapraced (CHF5074) is a novel -secretasemodulator, reduces A42 and A40 secretion, withan IC50 of 3.6 and 18.4 M, respectively.L-685458 is a p

46、otent transition state analog (TSA)-secretase inhibitor (GSI). L-685458 inhibitsamyloid -protein precursor -secretase activitywith IC of 17 nM, shows greater than 50-100-fold50selectivity over other aspartyl proteases tested.Purity: 98.0%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50

47、 mg, 100 mgPurity: 99.33%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg, 5 mg, 10 mg HYPERLINK https:/www.MedChemE/ly-411575.html LY-411575 HYPERLINK https:/www.MedChemE/ly-411575.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-2.html LY-411575 HYPERLINK https:/www.MedChemE/ly-4115

48、75-isomer-2.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-2.html (isomer HYPERLINK https:/www.MedChemE/ly-411575-isomer-2.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-2.html 2)Cat. No.: HY-50752 Cat. No.: HY-50752BLY-411575 is a potent -secretase inhibitor withIC of 0.078 nM/0.082 nM (m

49、embrane/cell-based),50and also inhibits Notch S3 cleavage with IC of500.39 nM.LY-411575 isomer 2 is an isomer of LY411575, whichis a potent -secretase inhibitor.Purity: 98.0%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.84%Clinical Data: No Development

50、ReportedSize: 10 mM 1 mL, 1 mg4 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/ly-411575-isomer-3.html LY-411575 HYPERLINK https:/www.MedChemE/ly-411575-isomer-3.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-3.html (isomer HYPERLINK https:/www.MedChemE/l

51、y-411575-isomer-3.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-3.html 3) HYPERLINK https:/www.MedChemE/ly-411575-isomer-3.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-1.html LY-411575 HYPERLINK https:/www.MedChemE/ly-411575-isomer-1.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-1

52、.html isomer HYPERLINK https:/www.MedChemE/ly-411575-isomer-1.html HYPERLINK https:/www.MedChemE/ly-411575-isomer-1.html 1Cat. No.: HY-50752C Cat. No.: HY-50752ALY-411575 isomer 3 is an isomer of LY411575, whichis a potent -secretase inhibitor.LY-411575 isomer 1 is an isomer of LY411575, whichis a p

53、otent -secretase inhibitor.Purity: 99.27%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mgPurity: 99.51%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mg HYPERLINK https:/www.MedChemE/MK-0752.html MK-0752 HYPERLINK https:/www.MedChemE/MK-0752.html HYPERLINK https:/www.MedChemE/

54、mrk-560.html MRK-560Cat. No.: HY-10974 Cat. No.: HY-14174MK-0752 is a potent, orally active and specific-secretase inhibitor, showing dose-dependentreduction of A40 with an IC of 5 nM in human50SH-SY5Y cells. MK-0752 crosses the blood-brainbarrier. MK-0752 reduces newly generated CNS A invivo.MRK-56

55、0 is a potent, orally bioavailable andbrain-penetrant -secretase inhibitor.Purity: 98.76%Clinical Data: Phase 4Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98.90%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/NGP555.html NGP555

56、Cat. No.: HY-108714 HYPERLINK https:/www.MedChemE/PF-3084014.html Nirogacestat(PF-3084014; PF-03084014) Cat. No.: HY-15185NGP555 is a -secretase modulator.Nirogacestat (PF-3084014) is a reversible, orallybioavailable, noncompetitive, and selective-secretase inhibitor with an IC of 6.2 nM.50Purity: 9

57、8.09%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.76%Clinical Data: Phase 3Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/nirogacestat-dihydrobromide.html Nirogacestat HYPERLINK https:/www.MedChemE/nirogacestat-dihydr

58、obromide.html HYPERLINK https:/www.MedChemE/nirogacestat-dihydrobromide.html dihydrobromide HYPERLINK https:/www.MedChemE/nirogacestat-dihydrobromide.html HYPERLINK https:/www.MedChemE/pf-06648671.html PF-06648671(PF-3084014 dihydrobromide; PF-03084014 dihydrobromide) Cat. No.: HY-15185BCat. No.: HY

59、-120789Nirogacestat dihydrobromide (PF-3084014dihydrobromide) is a reversible, orallybioavailable, noncompetitive, and selective-secretase inhibitor with an IC of 6.2 nM.50PF-06648671 is a novel, brainpenetrable, andorally active secretase modulator (GSM).PF-06648671 reduces A42 and A40, withconcomi

60、tant increases in A37 and A38 in vitro.PF-06648671 is used for the study of Alzheimersdisease.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg, 10 mg HYPERLINK https:/www.MedChemE/RO4929097.html RO4929097 HYPERLINK htt