Compounds > begacestat
Page last updated: 2024-08-02 19:08:05

begacestat

Description

Cross-References

ID SourceID
PubMed CID11269353
CHEMBL ID463981
SCHEMBL ID3314371
MeSH IDM0534279

Synonyms (35)

Synonym
bdbm28922
(2s)-n-(5-chlorothiophen-2-yl)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butane-2-sulfonamido
gsi-953
begacestat
D08869
begacestat (usan/inn)
769169-27-9
CHEMBL463981
2-thiophenesulfonamide, 5-chloro-n-((1s)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl)-
begacestat [usan:inn]
unii-3666c56bbu
3666c56bbu ,
5-chloro-n-((1s)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl)thiophene-2-sulfonamide
5-chloro-n-[(1s)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]thiophene-2-sulfonamide
begacestat [usan]
begacestat [inn]
gsi 953
5-chloro-n-[(1s)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]-2-thiophenesulfonamide
gtpl6979
5-chloro-n-[(2s)-4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl]thiophene-2-sulfonamide
DTXSID00227710
SCHEMBL3314371
5-chloro-n-[(1s)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoro-methyl)propyl]thiophene-2-sulfonamide
(s)-5-chloro-n-(4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl)thiophene-2-sulfonamide
AKOS024458073
begacestat, >=98% (hplc)
DB12263
Q27074993
CS-0003249
HY-14175
MS-26542
EN300-6745868
2-thiophenesulfonamide, 5-chloro-n-[(1s)-3,3,3-trifluoro-1-(hydroxymethyl)-2-(trifluoromethyl)propyl]-
E98924
Z2036684829

Protein Targets (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Presenilin-1Homo sapiens (human)IC500.0821AID1628299; AID1628300; AID1872649; AID475526; AID475551; AID731029; AID731030; AID754316; AID754317; AID755855; AID755856
Presenilin-2Homo sapiens (human)IC500.0821AID1628299; AID1628300; AID1872649; AID475526; AID475551; AID731029; AID731030; AID754316; AID754317; AID755855; AID755856
Gamma-secretase subunit APH-1BHomo sapiens (human)IC500.0821AID1628299; AID1628300; AID1872649; AID475526; AID475551; AID731029; AID731030; AID754316; AID754317; AID755855; AID755856
NicastrinHomo sapiens (human)IC500.0821AID1628299; AID1628300; AID1872649; AID475526; AID475551; AID731029; AID731030; AID754316; AID754317; AID755855; AID755856
Gamma-secretase subunit APH-1AHomo sapiens (human)IC500.0821AID1628299; AID1628300; AID1872649; AID475526; AID475551; AID731029; AID731030; AID754316; AID754317; AID755855; AID755856
Gamma-secretase subunit PEN-2Homo sapiens (human)IC500.0821AID1628299; AID1628300; AID1872649; AID475526; AID475551; AID731029; AID731030; AID754316; AID754317; AID755855; AID755856

Activation Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Presenilin-1Homo sapiens (human)EC500.0141AID1798946; AID1872652; AID1872653
Presenilin-2Homo sapiens (human)EC500.0136AID1872652; AID1872653
Gamma-secretase subunit APH-1BHomo sapiens (human)EC500.0136AID1872652; AID1872653
NicastrinHomo sapiens (human)EC500.0141AID1798946; AID1872652; AID1872653
Gamma-secretase subunit APH-1AHomo sapiens (human)EC500.0141AID1798946; AID1872652; AID1872653
Gamma-secretase subunit PEN-2Homo sapiens (human)EC500.0141AID1798946; AID1872652; AID1872653

Other Measurements

ProteinTaxonomyMeasurementAverage (mM)Bioassay(s)
Presenilin-1Homo sapiens (human)ED500.0078AID754313
Presenilin-2Homo sapiens (human)ED500.0078AID754313
Gamma-secretase subunit APH-1BHomo sapiens (human)ED500.0078AID754313
NicastrinHomo sapiens (human)ED500.0078AID754313
Gamma-secretase subunit APH-1AHomo sapiens (human)ED500.0078AID754313
Gamma-secretase subunit PEN-2Homo sapiens (human)ED500.0078AID754313

Bioassays (69)

Assay IDTitleYearJournalArticle
AID1872651Metabolic stability in human liver microsomes assessed as half life2022European journal of medicinal chemistry, Mar-15, Volume: 232ISSN: 1768-3254Small molecules targeting γ-secretase and their potential biological applications.
AID755849Oxidative metabolism in dog liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID1872653Inhibition of gamma-secretase (unknown origin) assessed as inhibition of Amyloid beta 42 production by cell-free assay2022European journal of medicinal chemistry, Mar-15, Volume: 232ISSN: 1768-3254Small molecules targeting γ-secretase and their potential biological applications.
AID1872654Ratio of drug concentration in Tg2576 mouse brain to plasma at 1 to 30 mg/kg, po2022European journal of medicinal chemistry, Mar-15, Volume: 232ISSN: 1768-3254Small molecules targeting γ-secretase and their potential biological applications.
AID755855Inhibition of partially purified human gamma-secretase-mediated cleavage of notch fusion protein measured after overnight incubation by ELISA2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID475546Half life in rat microsomes2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID754313Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis2013Bioorganic & medicinal chemistry letters, Feb-15, Volume: 23, Issue:4
ISSN: 1464-3405		Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors.
AID475545Half life in human microsomes2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID348070Metabolic stability in monkey microsomes assessed as half life2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID475576Inhibition of gamma secretase-mediated total amyloid beta production in plasma of patient with Alzheimer's disease at 450 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID755850Oxidative metabolism in mouse liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID348066Metabolic stability in Tg2576 mouse microsomes assessed as half life2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID475574AUC in transgenic 2576 mouse brain at 10 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID731030Inhibition of gamma-secretase (unknown origin) expressed in N2a NL/N cells coexpressing betaAPPNL and NotchdeltaE assessed as Abeta40 secretion by ELISA2013Journal of medicinal chemistry, Feb-28, Volume: 56, Issue:4
ISSN: 1520-4804		Effect of helical conformation and side chain structure on γ-secretase inhibition by β-peptide foldamers: insight into substrate recognition.
AID475547Half life in mouse microsomes2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475569Inhibition of gamma secretase-mediated total amyloid beta production in healthy human plasma at 600 mg/kg, po administered as single dose2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID1628299Inhibition of gamma secretase (unknown origin) mediated APP cleavage in CHO cells expressing APP Swedish KM/NL mutant assessed as reduction in amyloid beta 40 after 24 hrs by sandwich ELISA2016Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17
ISSN: 1520-4804		Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases.
AID475579AUC in brain of patient with Alzheimer's disease at 450 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID348068Metabolic stability in human microsomes assessed as half life2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID475517Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID1872650Selectivity ratio, ratio of IC50 for gamma-secretase (unknown origin) to IC50for Notch (unknown origin)2022European journal of medicinal chemistry, Mar-15, Volume: 232ISSN: 1768-3254Small molecules targeting γ-secretase and their potential biological applications.
AID1628301Selectivity ratio of IC50 for gamma secretase (unknown origin) mediated Notch M1726V mutant activation in CHO K1 cells to gamma secretase (unknown origin) mediated APP cleavage in CHO cells expressing APP Swedish KM/NL mutant2016Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17
ISSN: 1520-4804		Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases.
AID754316Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA2013Bioorganic & medicinal chemistry letters, Feb-15, Volume: 23, Issue:4
ISSN: 1464-3405		Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors.
AID755846Glucuronidation metabolism in mouse liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID731029Inhibition of gamma-secretase (unknown origin) expressed in N2a NL/N cells coexpressing betaAPPNL and NotchdeltaE assessed as Abeta42 secretion by ELISA2013Journal of medicinal chemistry, Feb-28, Volume: 56, Issue:4
ISSN: 1520-4804		Effect of helical conformation and side chain structure on γ-secretase inhibition by β-peptide foldamers: insight into substrate recognition.
AID754314Inhibition of gamma-secretase in CHO cells after overnight incubation by luciferase reporter gene assay2013Bioorganic & medicinal chemistry letters, Feb-15, Volume: 23, Issue:4
ISSN: 1464-3405		Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors.
AID754317Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA2013Bioorganic & medicinal chemistry letters, Feb-15, Volume: 23, Issue:4
ISSN: 1464-3405		Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors.
AID755813Reduction in amyloid beta (x to 40) in FVB mouse cortex at 1 mg/kg, po administered as single dose measured at 3 hrs2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID755843Glucuronidation metabolism in human liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID1872652Inhibition of gamma-secretase (unknown origin) assessed as inhibition of Amyloid beta 40 production by cell-free assay2022European journal of medicinal chemistry, Mar-15, Volume: 232ISSN: 1768-3254Small molecules targeting γ-secretase and their potential biological applications.
AID475570Ratio of drug level in plasma to CSF in healthy human at 600 mg/kg, po administered as single dose2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475577AUC in plasma of patient with Alzheimer's disease at 450 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID755812Reduction in amyloid beta (x to 40) in FVB mouse cortex at 3 mg/kg, po administered as single dose measured at 3 hrs2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID348072Dissociation constant, pKa of the compound2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID755854Selctivity ratio of IC50 for partially purified human gamma-secretase-mediated cleavage of notch fusion protein to IC50 for partially purified human gamma-secretase-mediated cleavage of MBP-APPc125Sw fusion protein2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID475548Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in transgenic 2576 mouse brain at 5 mg/kg, po after 4 hrs2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID755856Inhibition of partially purified human gamma-secretase-mediated cleavage of MBP-APPc125Sw fusion protein measured after overnight incubation by ELISA2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID348069Metabolic stability in dog microsomes assessed as half life2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID755848Oxidative metabolism in rat liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID755852Inhibition of gamma-secretase in CHO cells assessed expressing NotchdeltaE assessed as inhibition of notch cleavage after overnight incubation by luciferase reporter gene assay2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID755811Reduction in amyloid beta (x to 40) in FVB mouse cortex at 30 mg/kg, po administered as single dose measured at 3 hrs2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID475571Inhibition of gamma secretase-mediated total amyloid beta production in transgenic 2576 mouse plasma at 10 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475550Selectivity for gamma secretase-mediated amyloid beta (1 to 40) production over gamma secretase-mediated notch processing2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475551Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475573AUC in transgenic 2576 mouse plasma at 10 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475575AUC in transgenic 2576 mouse CSF at 10 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID755845Glucuronidation metabolism in dog liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID348053Inhibition of gamma-secretase expressed in CHO cells expressing human recombinant APP assessed as amyloid beta40 aggregation2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID755851Selctivity ratio of ED50 for gamma-secretase in CHO cells assessed expressing NotchdeltaE assessed as inhibition of notch cleavage to ED50 for gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID755844Glucuronidation metabolism in rat liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID475581Inhibition of gamma secretase-mediated total amyloid beta production in human plasma at 450 mg/kg measured at 2 hrs post-dose 2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID348055Reduction of amyloid beta40 level in Tg2576 mouse brain at 5 mg/kg, po after 4 hrs2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID754312Ratio of IC50 for gamma-secretase in CHO cells using Notch as substrate to ED50 for gamma-secretase in HEK293 cells using APP as substrate2013Bioorganic & medicinal chemistry letters, Feb-15, Volume: 23, Issue:4
ISSN: 1464-3405		Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors.
AID348067Metabolic stability in rat microsomes assessed as half life2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID475572Inhibition of gamma secretase-mediated total amyloid beta production in transgenic 2576 mouse brain at 10 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID1872655Toxicity in Sprague-Dawley rat assessed as maximum tolerated dose administered orally upto 28 days consecutively2022European journal of medicinal chemistry, Mar-15, Volume: 232ISSN: 1768-3254Small molecules targeting γ-secretase and their potential biological applications.
AID755810Reduction in amyloid beta (x to 40) in FVB mouse cortex at 10 mg/kg, po administered as single dose measured at 3 hrs2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID475526Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID348057Reduction of amyloid beta42 level in Tg2576 mouse brain at 5 mg/kg, po after 4 hrs2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID755853Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID348060Selectivity ratio of EC50 for gamma-secretase to EC50 for mouse notch processing2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.
AID1872649Inhibition of gamma-secretase (unknown origin) assessed as inhibition of Amyloid beta 40 production by cell-based assay2022European journal of medicinal chemistry, Mar-15, Volume: 232ISSN: 1768-3254Small molecules targeting γ-secretase and their potential biological applications.
AID1628300Inhibition of gamma secretase (unknown origin) mediated Notch M1726V mutant activation in CHO K1 cells after 48 hrs by chemiluminescence assay2016Journal of medicinal chemistry, 09-08, Volume: 59, Issue:17
ISSN: 1520-4804		Notch Antagonists: Potential Modulators of Cancer and Inflammatory Diseases.
AID755847Oxidative metabolism in human liver microsomes assessed as compound remaining2013Journal of medicinal chemistry, Jul-11, Volume: 56, Issue:13
ISSN: 1520-4804		Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007
AID754315Ratio of IC50 for gamma-secretase in human IMR32 cells using Notch as substrate to IC50 for gamma-secretase in human IMR-32 cells using APP as substrate2013Bioorganic & medicinal chemistry letters, Feb-15, Volume: 23, Issue:4
ISSN: 1464-3405		Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors.
AID475578AUC in CSF of patient with Alzheimer's disease at 450 mg/kg2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475582Inhibition of gamma secretase-mediated total amyloid beta production in human CSF at 450 mg/kg measured at 1 to 24 hrs post-dose 2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID475549Inhibition of gamma secretase-mediated amyloid beta (1 to 42) production in transgenic 2576 mouse brain at 5 mg/kg, po after 4 hrs2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
ISSN: 1520-4804		Recent advances in the identification of gamma-secretase inhibitors to clinically test the Abeta oligomer hypothesis of Alzheimer's disease.
AID1798946Cell-Based Assay for Amyloid-beta Accumulation from Article 10.1021/jm801252w: \\Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.\\2008Journal of medicinal chemistry, Dec-11, Volume: 51, Issue:23
ISSN: 1520-4804		Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease.

Research

Studies (11)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's4 (36.36)29.6817
2010's6 (54.55)24.3611
2020's1 (9.09)2.80

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews4 (36.36%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other7 (63.64%)84.16%
SubstanceStudiesClassesRolesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
7-amino-4-chloro-3-methoxy-2-benzopyran-1-one
1
isocoumarins201620168.0medium000010
propranolol
1
naphthalenes;
propanolamine;
secondary amine		anti-arrhythmia drug;
antihypertensive agent;
anxiolytic drug;
beta-adrenergic antagonist;
environmental contaminant;
human blood serum metabolite;
vasodilator agent;
xenobiotic		2013201311.0low000010
tarenflurbil
2
flurbiprofen2009201611.5medium000110
n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
2
carboxylic ester;
difluorobenzene;
dipeptide;
tert-butyl ester		EC 3.4.23.46 (memapsin 2) inhibitor2008201612.0low000110
l 685458
2
carbamate ester;
monocarboxylic acid amide;
peptide;
secondary alcohol		EC 3.4.23.46 (memapsin 2) inhibitor;
peptidomimetic		2009201611.5low000110
mk 0752
1
201620168.0medium000010
ly 450139
5
peptide2008202210.4high000221
chf 5074
1
202220222.0low000001
ly 411575
3
dibenzoazepine;
difluorobenzene;
lactam;
secondary alcohol		EC 3.4.23.46 (memapsin 2) inhibitor200920228.3high000111
4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acid
2
sulfonamide2009201611.5medium000110
mrk 560
2
2009201611.5medium000110
pf 3084014
1
201620168.0low000010
bms 708163
3
oxadiazole;
ring assembly		2009201312.3medium000120
ro 4929097
1
dibenzoazepine;
dicarboxylic acid diamide;
lactam;
organofluorine compound		EC 3.4.23.46 (memapsin 2) inhibitor201620168.0medium000010
(r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline
2
2013201311.0high000020
SubstanceStudiesClassesRolesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
alanine
1
alanine zwitterion;
alanine;
L-alpha-amino acid;
proteinogenic amino acid;
pyruvate family amino acid		EC 4.3.1.15 (diaminopropionate ammonia-lyase) inhibitor;
fundamental metabolite		2013201311.0low000010
valine
1
L-alpha-amino acid zwitterion;
L-alpha-amino acid;
proteinogenic amino acid;
pyruvate family amino acid;
valine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite		2009200915.0low000100
thiophenes
5
mancude organic heteromonocyclic parent;
monocyclic heteroarene;
thiophenes;
volatile organic compound		non-polar solvent2008201313.8medium000320
oxadiazoles
1
2013201311.0low000010
pf 3084014
1
2009200915.0low000100
bms 708163
1
oxadiazole;
ring assembly		2013201311.0low000010
ConditionIndicatedStudiesFirst YearLast YearAverage AgeRelationship StrengthTrialspre-19901990's2000's2010'spost-2020
Acute Confusional Senile Dementia0
7
2008202212.3high000421
Alzheimer Disease1
7
2008202212.3high000421
Benign Neoplasms0
1
201620168.0low000010
Carcinogenesis0
1
201620168.0low000010
Cirrhosis0
1
201620168.0low000010
Disease Models, Animal0
1
2008200816.0low000100
Fibrosis0
1
201620168.0low000010
Inflammation0
1
201620168.0low000010
Innate Inflammatory Response0
1
201620168.0low000010
Neoplasms0
1
201620168.0low000010