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Compound Detail

CHEMBL520733

SEMAGACESTAT
🧪 Phase III
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🧪 Phase III
CC(C)[C@H](O)C(=O)N[C@@H](C)C(=O)N[C@@H]1C(=O)N(C)CCc2ccccc21
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL520733
Name SEMAGACESTAT
Phase Phase III
Structure Type MOL
InChI Key PKXWXXPNHIWQHW-RCBQFDQVSA-N

Known Names

LY-450139 LY450139 Semagacestat
3
Targets
20
Activities
2
Assay Types
1
PK Parameters
20
Publications
3
Known Names
1
Indications
1
Mechanisms

Molecular Properties

361.4
MW (Da)
0.38
ALogP
4
HBA
3
HBD
98.7
PSA (Ų)
0.71
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Natural Product
USAN Stem -stat
USAN Year 2007

Extended Properties

Molecular Formula C19H27N3O4
MW 361.44
Aromatic Rings 1
Heavy Atoms 26
NP-Likeness -0.24

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Gamma-secretase inhibitor INHIBITOR Gamma-secretase ✓ ✓

Indications

Alzheimer Disease

Activity Summary

IC50 16 meas. best 8.49
EC50 4 meas. best 7.55

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Gamma-secretase
CHEMBL2094135
 IC50 8.49 7.55 3.2 12
Unchecked
CHEMBL612545
 IC50 7.85 7.39 14.1 3
Unchecked
CHEMBL612545
 EC50 7.55 7.375 28.0 2
Gamma-secretase
CHEMBL2094135
 EC50 6.9 6.9 125.9 1
Cryptosporidium parvum
CHEMBL612855
 EC50 5.38 5.38 4200.0 1

Pharmacokinetic Data

Parameter Value Units Species
T1/2 2.5 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Gamma-secretase IC50 = 3.2 nM 8.49 Inhibition of partially purified human gamma-secretase-mediated cleavage of notc... 23713656
Gamma-secretase IC50 = 7.9 nM 8.1 Inhibition of partially purified human gamma-secretase-mediated cleavage of MBP-... 23713656
Gamma-secretase IC50 = 10.9 nM 7.96 Inhibition of gamma secretase (unknown origin) 27045975
Gamma-secretase IC50 = 10.9 nM 7.96 Inhibition of gamma-secretase in human H4 cells assessed as reduction in amyloid... 35176561
Gamma-secretase IC50 = 14.1 nM 7.85 Inhibition of gamma secretase (unknown origin) mediated Notch signaling 27045975
Unchecked IC50 = 14.1 nM 7.85 Inhibition of Notch in human H4 cells 35176561
Unchecked IC50 = 15.0 nM 7.82 Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production 19694467
Unchecked EC50 = 28.0 nM 7.55 Inhibition of gamma-secretase expressed in CHO cells expressing wild type human ... 18556202
Gamma-secretase IC50 = 38.0 nM 7.42 Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in huma... 19694467
Gamma-secretase IC50 = 38.0 nM 7.42 Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan... 19694467
Gamma-secretase IC50 = 39.81 nM 7.4 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant... 20056541
Gamma-secretase IC50 = 39.81 nM 7.4 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant... 20056541
Unchecked EC50 = 63.0 nM 7.2 Inhibition of mouse notch expressed in CHO cells assessed as transactivation of ... 18556202
Gamma-secretase IC50 = 100.0 nM 7.0 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant... 20056541
Gamma-secretase EC50 = 125.89 nM 6.9 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant... 20056541
Gamma-secretase IC50 = 125.89 nM 6.9 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant... 20056541
Gamma-secretase IC50 = 199.53 nM 6.7 Inhibition of gamma-secretase in human SHSY5Y cells expressing human recombinant... 20056541
Unchecked IC50 = 316.23 nM 6.5 Inhibition of gamma-secretase expressed in african green monkey CV1 cells coexpr... 20056541
Cryptosporidium parvum EC50 = 4200.0 nM 5.38 Antiparasitic activity against Cryptosporidium parvum assessed as parasitic grow... 37196868

Literature References

PubMed DOI Target Context # Activities
20056541 10.1016/j.bmcl.2009.08.072 Gamma-secretase 8
19694467 10.1021/jm900188z Homo sapiens 6
29477076 10.1016/j.ejmech.2018.02.035 Homo sapiens 4
23713656 10.1021/jm301741t Liver 4
23713656 10.1021/jm301741t Mus musculus 4
23713656 10.1021/jm301741t Liver microsomes 4
18556202 10.1016/j.bmcl.2008.05.064 Unchecked 3
- 10.6019/CHEMBL3301361 ADMET 3
23713656 10.1021/jm301741t Gamma-secretase 3
23713656 10.1021/jm301741t Unchecked 3
- 10.6019/CHEMBL4495565 SARS-CoV-2 2
27045975 10.1021/acs.jmedchem.5b01516 Gamma-secretase 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
35176561 10.1016/j.ejmech.2022.114169 Mus musculus 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
19694467 10.1021/jm900188z Gamma-secretase 2
37196868 10.1016/j.bmcl.2023.129328 Cryptosporidium parvum 1
20056541 10.1016/j.bmcl.2009.08.072 SH-SY5Y 1
20056541 10.1016/j.bmcl.2009.08.072 Unchecked 1
19443228 10.1016/j.bmc.2009.04.052 Gamma-secretase 1

Data from ChEMBL 36 via Core Engine