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Compound Detail

CHEMBL175247

ORLISTAT
💊 Approved Drug
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💊 Approved Drug
CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](CC(C)C)NC=O

Basic Information

ChEMBL ID CHEMBL175247
Name ORLISTAT
Phase Approved
Structure Type MOL
InChI Key AHLBNYSZXLDEJQ-FWEHEUNISA-N
Therapeutic ✓ Yes

Known Names

Alli Alli (previously orlistat gsk) Beacita Lipstatin NSC-758881 Orlipastat Orlistat RO 18-0647/002 Ro-18-0647-002 RO-18-0647/002 RO-180647-002 RO-180647002 +2 more
22
Targets
66
Activities
3
Assay Types
8
PK Parameters
20
Publications
14
Known Names
5
Indications
2
Mechanisms

Molecular Properties

495.8
MW (Da)
6.88
ALogP
5
HBA
1
HBD
81.7
PSA (Ų)
0.09
QED
1
Ro5 Violations
23
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1998
Availability OTC
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product
USAN Stem -stat
USAN Year 1991

Extended Properties

Molecular Formula C29H53NO5
MW 495.75
Aromatic Rings 0
Heavy Atoms 35
NP-Likeness 1.18

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Gastric lipase inhibitor INHIBITOR Gastric triacylglycerol lipase
Pancreatic lipase inhibitor INHIBITOR Pancreatic triacylglycerol lipase

Indications

Obesity Infertility Hyperlipoproteinemia Type I Polycystic Ovary Syndrome Metabolic Syndrome

ATC Classification

A08AB01
orlistat
Level 1: ALIMENTARY TRACT AND METABOLISM
Level 2: ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS

Activity Summary

IC50 61 meas. best 8.8
Ki 3 meas. best 6.55
EC50 2 meas. best 5.8

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Pancreatic triacylglycerol lipase
CHEMBL1812
IC50 8.8 7.466 1.6 5
Hepatic triacylglycerol lipase
CHEMBL2127
IC50 8.52 8.52 3.0 1
Pancreatic triacylglycerol lipase
CHEMBL1687677
IC50 8.4 6.7088 4.0 16
Endothelial lipase
CHEMBL5080
IC50 8.22 8.22 6.0 1
Diacylglycerol lipase-alpha
CHEMBL5545
IC50 8.0 7.0733 10.0 3
Fatty-acid amide hydrolase 1
CHEMBL3229
IC50 8.0 8.0 10.0 1
Unchecked
CHEMBL612545
IC50 8.0 6.1757 10.0 7
Monoacylglycerol lipase ABHD6
CHEMBL2189127
IC50 7.88 7.5457 13.2 7
Diacylglycerol lipase-alpha
CHEMBL5180
IC50 7.7 7.7 20.0 1
Phosphatidylserine lipase ABHD16A
CHEMBL6168
IC50 7.52 7.145 30.0 2
Platelet-activating factor acetylhydrolase
CHEMBL3514
IC50 7.3 7.3 50.0 1
Diacylglycerol lipase-beta
CHEMBL5521
IC50 7.22 6.8 60.0 2
Lipoprotein lipase
CHEMBL2060
IC50 7.18 7.18 66.0 1
Lysophosphatidylserine lipase ABHD12
CHEMBL5516
IC50 7.1 6.796 80.0 5
Fatty acid synthase
CHEMBL4158
Ki 6.55 6.55 280.0 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
EC50 5.8 5.175 1600.0 2
Cannabinoid receptor 1
CHEMBL218
Ki 5.6 5.6 2500.0 1
Giardia intestinalis
CHEMBL612652
IC50 5.55 5.55 2800.0 1
Fatty acid synthase
CHEMBL4158
IC50 5.33 5.33 4630.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 5.07 5.07 8450.0 1
Pancreatic triacylglycerol lipase
CHEMBL1687677
Ki 5.01 5.01 9800.0 1
MDA-MB-231
CHEMBL400
IC50 4.89 4.89 13000.0 1
MDA-MB-435
CHEMBL614697
IC50 4.78 4.78 16800.0 1
ADMET
CHEMBL612558
IC50 4.15 4.15 70200.0 1

Pharmacokinetic Data

Parameter Value Units Species
PPB 1.0 % Homo sapiens
T1/2 0.008667 hr Homo sapiens
T1/2 0.009833 hr Canis lupus familiaris
T1/2 0.006667 hr Cavia porcellus
T1/2 0.009167 hr Homo sapiens
T1/2 0.02767 hr Sus scrofa
T1/2 0.02733 hr Homo sapiens
T1/2 1.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Pancreatic triacylglycerol lipase IC50 = 1.57 nM 8.8 Negative allosteric modulator activity at human Pancreatic lipase using DDAO-ol ... 37490786
Hepatic triacylglycerol lipase IC50 = 3.0 nM 8.52 Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containi... 30613337
Pancreatic triacylglycerol lipase IC50 = 4.0 nM 8.4 Inhibition of porcine pancreatic lipase using p-nitrophenyl butyrate as substrat... 29541373
Pancreatic triacylglycerol lipase IC50 = 4.0 nM 8.4 Inhibition of porcine pancreatic lipase using p-NPB as substrate pretreated for ... 29667821
Pancreatic triacylglycerol lipase IC50 = 6.0 nM 8.22 Inhibition of recombinant human PL expressed in HEK293F cells using PED-A1 conta... 30613337
Endothelial lipase IC50 = 6.0 nM 8.22 Inhibition of endothelial lipase in human HT1080 cells using PED-A1 containing D... 30613337
Diacylglycerol lipase-alpha IC50 = 10.0 nM 8.0 Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG ... 22738638
Fatty-acid amide hydrolase 1 IC50 = 10.0 nM 8.0 Inhibition of rat histidine tagged FAAH expressed in Escherichia coli by coumari... 22738638
Unchecked IC50 = 10.0 nM 8.0 Inhibition of Lipase (unknown origin) 33766763
Pancreatic triacylglycerol lipase IC50 = 12.0 nM 7.92 Inhibition of porcine pancreatic lipase using p-nitrophenyl butyrate as substrat... 27156775
Monoacylglycerol lipase ABHD6 IC50 = 13.18 nM 7.88 Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10... 26344596
Monoacylglycerol lipase ABHD6 IC50 = 14.13 nM 7.85 Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10... 26344596
Diacylglycerol lipase-alpha IC50 = 20.0 nM 7.7 Inhibition of DAGLalpha in mouse N18TG2 cells assessed as inhibition of ionomyci... 26917221
Monoacylglycerol lipase ABHD6 IC50 = 19.95 nM 7.7 Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10... 26344596
Phosphatidylserine lipase ABHD16A IC50 = 30.0 nM 7.52 Inhibition of recombinant BAT5 transfected in HEK293T cells by SDS-PAGE using rh... 18657971
Pancreatic triacylglycerol lipase IC50 = 33.0 nM 7.48 Inhibition of pancreatic lipase (unknown origin) by spectrophotometeric analysis 38052378
Monoacylglycerol lipase ABHD6 IC50 = 37.15 nM 7.43 Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10... 26344596
Monoacylglycerol lipase ABHD6 IC50 = 48.0 nM 7.32 Inhibition of human ABHD6 expressed in HEK293 cells using TAMRA-FP as substrate ... 32371333
Monoacylglycerol lipase ABHD6 IC50 = 47.86 nM 7.32 Inhibition of human ABHD6 containing pCMV6-AC-hABHD6 transfected into HEK293 cel... 25752982
Monoacylglycerol lipase ABHD6 IC50 = 48.0 nM 7.32 Inhibition of human ABHD6 containing pCMV6-AC-hABHD6 transfected into HEK293 cel... 25752982

Literature References

PubMed DOI Target Context # Activities
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
23141914 10.1016/j.bmcl.2012.10.046 Mus musculus 12
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
22738638 10.1016/j.bmcl.2012.05.101 Diacylglycerol lipase-alpha 10
18363378 10.1021/np8000333 Mus musculus 9
16180814 10.1021/np0580614 Mus musculus 9
23153815 10.1016/j.ejmech.2012.10.040 Pancreatic triacylglycerol lipase 8
23153815 10.1016/j.ejmech.2012.10.040 Pancreatic lipase-related protein 2 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
27908755 10.1016/j.bmc.2016.11.031 Pancreatic triacylglycerol lipase 7
20966043 10.1124/dmd.110.035105 Nuclear receptor subfamily 1 group I member 2 6
16644217 10.1016/j.bmcl.2006.03.102 Mus musculus 6
- 10.6019/CHEMBL4495565 SARS-CoV-2 6
23153815 10.1016/j.ejmech.2012.10.040 Gastric triacylglycerol lipase 5
26344596 10.1016/j.bmc.2015.08.030 Monoacylglycerol lipase ABHD6 5
23153815 10.1016/j.ejmech.2012.10.040 Bile salt-activated lipase 4
18657971 10.1016/j.bmcl.2008.06.091 Diacylglycerol lipase-beta 4
22738638 10.1016/j.bmcl.2012.05.101 Unchecked 4
33071055 10.1016/j.ejmech.2020.112908 Unchecked 4
18657971 10.1016/j.bmcl.2008.06.091 Diacylglycerol lipase-alpha 4

Data from ChEMBL 36 via Core Engine