orlistat   Click here for help

GtoPdb Ligand ID: 5277

Synonyms: Alli® | tetrahydrolipstatin | THL | Xenical®
Approved drug
orlistat is an approved drug (FDA (1999), EMA (1998))
Compound class: Synthetic organic
Comment: Orlistat is a lipase inhibitor. Lipase enzymes include gastric and pancreatic lipases, diacylglycerol lipase (DAGL) and αβ-hydrolase 12 (ABHD12). It is used as an anti-obesity drug treatment. At least 18 isomeric forms exist in PubChem.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: orlistat

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 24
Topological polar surface area 81.7
Molecular weight 495.39
XLogP 10.26
No. Lipinski's rules broken 2

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCCCCCCCCCCC(CC1OC(=O)C1CCCCCC)OC(=O)C(CC(C)C)NC=O
Isomeric SMILES CCCCCCCCCCC[C@@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)OC(=O)[C@H](CC(C)C)NC=O
InChI InChI=1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1
InChI Key AHLBNYSZXLDEJQ-FWEHEUNISA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
Primary target is pancreatic triacylglycerol lipase (P16233) but this compound also inhibits Sn1-specific diacylglycerol lipases α (Q9Y4D2) and β (Q8NCG7).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
fatty acid synthase Hs Inhibitor Inhibition 6.6 pKi - 1
⤷ pKi 6.6 (Ki 2.8x10-7 M) [1]
Description: Inhibition of recombinant FASN thioesterase domain by fluorogenic assay
pancreatic lipase Primary target of this compound Hs Inhibitor Inhibition 8.9 pIC50 - 3
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [3]
diacylglycerol lipase α Hs Inhibitor Inhibition 7.2 pIC50 - 2
⤷ pIC50 7.2 (IC50 6x10-8 M) [2]
αβ-Hydrolase 12 Hs Inhibitor Inhibition 7.1 pIC50 - 5
⤷ pIC50 7.1 (IC50 8x10-8 M) [5]
Description: Inhibition of recombinant ABHD12 expressed in HEK293T cells, by SDS-PAGE using rhodamine-tagged FP probe.
diacylglycerol lipase β Hs Inhibitor Inhibition 7.0 pIC50 - 2
⤷ pIC50 7.0 (IC50 1x10-7 M) [2]
fatty acid synthase Hs Inhibitor Inhibition 5.9 pIC50 - 6
⤷ pIC50 5.9 (IC50 1.35x10-6 M) [6]
Description: Inhibition of FAS thioesterase domain by fluorogenic assay
Targets where the ligand is described in the comment field
Target Comment
fatty acid synthase Fatty acid synthase (FAS; FASN) is a component of the fatty acid biosynthesis pathway. Pharmacological inhibition of FAS using the FAS/gastric lipases inhibitor orlistat has been shown to decrease replication SARS-CoV-2 in vitro [4,7].