ORLISTAT

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Trade Names
Synonyms
Status
Molecule Category UNKNOWN
ATC A08AB01
UNII 95M8R751W8
EPA CompTox DTXSID8023395

Structure

InChI Key AHLBNYSZXLDEJQ-FWEHEUNISA-N
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

Physicochemical Descriptors

Property Name Value
Molecular Formula C29H53NO5
Molecular Weight 495.75
AlogP 6.88
Hydrogen Bond Acceptor 5.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 23.0
Polar Surface Area 81.7
Molecular species NEUTRAL
Aromatic Rings 0.0
Heavy Atoms 35.0

Bioactivity

Mechanism of Action Action Reference
Gastric lipase inhibitor INHIBITOR DailyMed
Protein: Pancreatic lipase
Description: Pancreatic triacylglycerol lipase
Organism : Homo sapiens
P16233 ENSG00000175535
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Hydrolase
- 4-990 - 9800 55-96
Enzyme Transferase
- 4630 - 280 52-60
Enzyme
- 4-990 - 280 55-96
Membrane receptor Family A G protein-coupled receptor Small molecule receptor (family A GPCR) Lipid-like ligand receptor (family A GPCR) Cannabinoid receptor
- - - 2500 -
Transcription factor Nuclear receptor Nuclear hormone receptor subfamily 1 Nuclear hormone receptor subfamily 1 group I Nuclear hormone receptor subfamily 1 group I member 2
1600-28200 - - - -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC21/SLCO family of organic anion transporting polypeptides
- - - - 85
Assay Description Organism Bioactivity Reference
Compound was tested for inhibition of porcine pancreatic lipase Sus scrofa 0.4 ug.mL-1
Binding affinity for cannabinoid receptor 1 None 100.0 nM
Inhibition of pancreatic lipase assessed as umoles of oleic acic released per millimiter of triolein per hour None 0.04 ug.mL-1
Inhibition of ionomycin-induced stimulation of 2-AG biosynthesis in mouse N18TG2 cells at 1 uM Mus musculus 79.8 %
Inhibition of ABHD12 in mouse brain assessed as reduction in spectral count at 5 uM treated for 30 mins by ABPP-MudPIT assay relative to control Mus musculus 60.0 %
Inhibition of BAT5 in mouse brain assessed as reduction in spectral count at 5 uM treated for 30 mins by ABPP-MudPIT assay relative to control Mus musculus 60.0 %
Inhibition of PLA2g7 in mouse brain assessed as reduction in spectral count at 50 uM treated for 30 mins by ABPP-MudPIT assay relative to control Mus musculus 60.0 %
Inhibition of TPP2 in mouse brain assessed as reduction in spectral count at 5 uM treated for 30 mins by ABPP-MudPIT assay relative to control Mus musculus 60.0 %
Inhibition of recombinant BAT5 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe None 30.0 nM
Inhibition of recombinant ABHD12 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe None 80.0 nM
Inhibition of recombinant PLA2g7 transfected in HEK293T cells by SDS-PAGE using rhodamine-tagged FP probe None 50.0 nM
Inhibition of human recombinant DAGLalpha overexpressed in african green monkey COS7 cells Homo sapiens 60.0 nM
Inhibition of human recombinant DAGLbeta overexpressed in african green monkey COS7 cells Homo sapiens 60.0 nM
Inhibition of pig pancreatic lipase assessed as p-NPB hydrolysis by ELISA Sus scrofa 600.0 nM
Inhibition of porcine pancreatic lipase using p-nitrophenylbutyrate as substrate at 1 uM preincubated for 15 mins prior substrate addition measured after 15 mins by spectrophotometry Sus scrofa 60.4 %
Inhibition of porcine pancreatic lipase using p-nitrophenylbutyrate as substrate preincubated for 15 mins prior substrate addition measured after 15 mins by spectrophotometry Sus scrofa 300.0 nM
Inhibition of porcine pancreatic lipase using micellar solution of triolein as substrate preincubated for 5 mins before substrate addition measured after 30 mins Sus scrofa 220.0 nM
Inhibition of porcine pancreatic lipase using micellar solution of triolein as substrate at 0.4 uM preincubated for 5 mins before substrate addition measured after 30 mins Sus scrofa 55.0 %
Antagonist activity at recombinant FASN thioesterase domain by fluorogenic assay None 280.0 nM
Inhibition of electric eel AChE at 2 mg/ml by Ellman's method Electrophorus electricus -6.52 %
Inhibition of horse BChE at 2 mg/ml by Ellman's method Equus caballus 7.43 %
Inhibition of porcine Pancrelipase at 400 molar excess after 30 mins Sus scrofa 93.1 %
Inhibition of human pancreatic CEH at 20 molar excess after 30 mins Homo sapiens 83.6 %
Inhibition of human pancreatic CEH at 2 molar excess after 30 mins Homo sapiens 80.1 %
Inhibition of recombinant DGL expressed in transgenic maize at 20 molar excess after 30 mins in presence of NaTDC Canis lupus familiaris 56.3 %
Inhibition of recombinant DGL expressed in transgenic maize at 2 molar excess after 30 mins in presence of NaTDC Canis lupus familiaris 51.5 %
Inhibition of recombinant GPLRP2 expressed in Aspergillus oryzae at 20 molar excess after 30 mins in presence of NaTDC Cavia porcellus 87.3 %
Inhibition of recombinant GPLRP2 expressed in Aspergillus oryzae at 2 molar excess after 30 mins in presence of NaTDC Cavia porcellus 82.7 %
Inhibition of recombinant HPLRP2 expressed in Pichia pastoris at 20 molar excess after 30 mins in presence of NaTDC Homo sapiens 86.3 %
Inhibition of recombinant HPLRP2 expressed in Pichia pastoris at 2 molar excess after 30 mins in presence of NaTDC Homo sapiens 83.6 %
Inhibition of PPL at 400 molar excess after 30 mins in presence of NaTDC Sus scrofa 90.9 %
Inhibition of PPL at 100 molar excess after 30 mins in presence of NaTDC Sus scrofa 85.5 %
Inhibition of recombinant HPL expressed in Pichia pastoris at 400 molar excess after 30 mins in presence of NaTDC Homo sapiens 85.0 %
Inhibition of recombinant HPL expressed in Pichia pastoris at 100 molar excess after 30 mins in presence of NaTDC Homo sapiens 77.2 %
Inhibition of recombinant DGL expressed in transgenic maize assessed as hydrolysis of trybutyrin emulsion at 10 to 40 molar excess after 30 mins in presence of NaTDC Canis lupus familiaris 60.0 %
Inhibition of porcine pancreatic lipase type 2 by FRET assay Sus scrofa 1.0 nM
Inhibition of porcine pancreatic lipase type 2 at 10 uM by FRET assay Sus scrofa 98.0 %
Inhibition of bacterial lipoprotein lipase by FRET assay Bacteria 100.0 nM
Inhibition of bacterial lipoprotein lipase at 10 uM by FRET assay Bacteria 92.0 %
Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate in detergent free solution by FRET assay Homo sapiens 10.0 nM
Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 10 uM in detergent free solution by FRET assay Homo sapiens 92.0 %
Inhibition of mouse DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 10000 nM by scintillation counting based radio-TLC assay Mus musculus 98.0 %
Inhibition of mouse DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 1000 nM by scintillation counting based radio-TLC assay Mus musculus 92.0 %
Inhibition of mouse DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 100 nM by scintillation counting based radio-TLC assay Mus musculus 72.0 %
Inhibition of mouse DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 10 nM by scintillation counting based radio-TLC assay Mus musculus 55.0 %
Inhibition of human N-terminal histidine tagged full length MAGL expressed in Escherichia coli at 10 uM by by coumarin ester substrate fluorescence assay Homo sapiens 47.0 %
Inhibition of rat histidine tagged FAAH expressed in Escherichia coli by coumarin ester substrate fluorescence assay Rattus norvegicus 10.0 nM
Inhibition of rat histidine tagged FAAH expressed in Escherichia coli at 10 uM by coumarin ester substrate fluorescence assay Rattus norvegicus 6.0 %
Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 10 uM in presence of 0.05% Triton X-100 by scintillation counting based radio-TLC assay Homo sapiens 100.0 %
Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 10 uM in detergent free solution by scintillation counting based radio-TLC assay Homo sapiens 100.0 %
Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 10 uM using JZL184 pretreated protein in detergent free solution by FRET assay Homo sapiens 86.0 %
Inhibition of human DAGLalpha expressed in HEK293T cell membrane using [14C]SAG substrate at 10 uM in presence of 0.05% Triton X-100 by FRET assay Homo sapiens 99.0 %
Inhibition of Sus scrofa (pig) pancreatic lipase type 2 using PNPB as substrate pre-incubated with enzyme for 5 min prior to substrate addition measured for 5 min by spectrophotometric analysis Sus scrofa 0.21 ug.mL-1
Inhibition of pig pancreatic lipase assessed as hydrolysis of p-nitrophenylbutyrate to p-nitrophenol Sus scrofa 600.0 nM
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM Cricetulus griseus 85.27 %
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM Cricetulus griseus 84.62 %
Inhibition of human ABHD6 containing pCMV6-AC-hABHD6 transfected into HEK293 cells Homo sapiens 47.86 nM Inhibition of human ABHD6 containing pCMV6-AC-hABHD6 transfected into HEK293 cells Homo sapiens 48.0 nM
Inhibition of human ABHD12 containing pCMV6-XL4-hABHD12 transfected into HEK293 cells Homo sapiens 190.55 nM Inhibition of human ABHD12 containing pCMV6-XL4-hABHD12 transfected into HEK293 cells Homo sapiens 190.0 nM
Inhibition of porcine pancreatic lipase using p-nitrophenylbutyrate as substrate assessed as formation of p-nitrophenol preincubated for 15 mins followed by substrate addition measured after 15 mins Sus scrofa 300.0 nM
Inhibition of porcine pancreatic lipase pre-incubated for 15 mins before p-nitrophenylbutyrate substrate addition by microplate reader based method Sus scrofa 320.0 nM
Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 10 mins by HPLC method Homo sapiens 13.18 nM
Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 30 mins by HPLC method Homo sapiens 14.13 nM
Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 60 mins by HPLC method Homo sapiens 19.95 nM
Inhibition of human ABHD6 expressed in HEK293 cells at 1 uM pre-incubated for 10 mins before 2-AG substrate addition followed by rapid 40 fold compound dilution measured after 90 mins by HPLC method Homo sapiens 37.15 nM
Inhibition of human ABHD12 expressed in HEK293 cells pre-incubated for 10 mins before 2-AG substrate addition by HPLC method Homo sapiens 190.55 nM Inhibition of human ABHD12 expressed in HEK293 cells pre-incubated for 10 mins before 2-AG substrate addition by HPLC method Homo sapiens 190.0 nM
Inhibition of human recombinant DAGLalpha expressed in African green monkey COS cells using sn-1-stearoyl-2-[14C]-arachidonoyl-glycerol as substrate incubated for 15 mins by beta counting analysis Homo sapiens 1.0 nM
Inhibition of DAGLalpha in mouse N18TG2 cells assessed as inhibition of ionomycin-induced formation of 2-AG incubated for 20 mins by LC-MS analysis Mus musculus 20.0 nM
Inhibition of DAGLbeta (unknown origin) Homo sapiens 420.0 nM
Inhibition of porcine pancreatic lipase using p-nitrophenyl butyrate as substrate assessed as formation of p-nitrophenol preincubated for 10 mins followed by substrate addition by spectrophotometric method Sus scrofa 12.0 nM
Inhibition of porcine pancreatic lipase assessed as reduction in 4-nitrophenol formation from 4-nitrophenyl butyrate substrate preincubated for 30 mins followed by substrate addition measured after 5 mins by spectrophotometer Sus scrofa 990.0 nM
Inhibition of pancreatic lipase (unknown origin) using p-nitrophenylbutyrate as substrate preincubated for 10 mins followed by substrate addition measured after 20 mins Homo sapiens 310.0 nM
Inhibition Assay: Particularly, pancreatic lipase inhibiting activity was measured by the conventional method known to those in the art (Kim, J. H.; Kim, H. J.; Park, H. W.; Youn, S. H.; Choi, D. Y.; Shin, C. S. FEMS Microbiol. Lett. 2007, 276, 93.). To prepare the enzyme buffer, 30 mL (10 units) of pig pancreatic lipase solution (Sigma, St. Louis, Mo.) and 1 mM EDTA (pH 6.8) were mixed with 10 mM MOPS (morpholinepropanesulphonic acid), which was added to 850 mL of tris buffer (100 mM Tris-HCl and 5 mM CaCl2, pH 7.0). Then, 100 mL of the rotenoisin A or B of the present invention was mixed with the prepared enzyme buffer at the experimental concentration. As the positive control, 880 mL of Orlistat (Roche, Basel, Switzerland) was mixed with the enzyme buffer. 20 mL of substrate solution containing 20 mM p-nitrophenylbutyrate dissolved in dimethyl formaide was added to the enzyme buffer, followed by culture for 15 minutes at 37° C. that was the temperature adequate for enzyme reaction. None 600.0 nM
Inhibition of porcine pancreatic lipase using p-nitrophenyl butyrate as substrate preincubated for 5 mins followed by substrate addition measured after 5 mins by spectrophotometric analysis Sus scrofa 990.0 nM
Inhibition of porcine pancreatic lipase using p-nitrophenyl butyrate as substrate pretreated for 15 mins followed by substrate addition and measured after 60 mins Sus scrofa 800.0 nM
Inhibition of human pancreatic lipase using emulsified olive oil as substrate pretreated with substrate for 5 mins followed by enzyme addition and measured after 30 mins Homo sapiens 190.0 nM
Inhibition of porcine pancreatic lipase using p-nitrophenyl butyrate as substrate after 20 mins Sus scrofa 4.0 nM
Inhibition of porcine pancreatic lipase using triolein as substrate measured after 10 mins Sus scrofa 360.0 nM
Inhibition of porcine pancreatic lipase using p-NPB as substrate pretreated for 15 mins followed by substrate addition measured after 15 mins by spectrophometric method Sus scrofa 4.0 nM
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600) Staphylococcus aureus subsp. aureus 11.59 %
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600) Escherichia coli -4.78 %
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600) Klebsiella pneumoniae 7.06 %
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600) Pseudomonas aeruginosa 39.77 %
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600 Acinetobacter baumannii 17.79 %
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630 Candida albicans 1.01 %
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570) Cryptococcus neoformans -4.7 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens -3.03 %
Inhibition of ABHD16A (unknown origin) Homo sapiens 170.0 nM
Inhibition of endothelial lipase in human HT1080 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay Homo sapiens 6.0 nM
Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay Homo sapiens 3.0 nM
Inhibition of recombinant human LPL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay Homo sapiens 66.0 nM
Inhibition of recombinant human PL expressed in HEK293F cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay Homo sapiens 6.0 nM
Inhibition of porcine pancreatic lipase using pNPB as substrate measured after 30 mins Sus scrofa 400.0 nM
Inhibition of full length human FASN transfected in HeLa cell lysates at 10 uM using acetyl Co-A/malonyl Co-A as substrate preincubated with enzyme for 2 hrs followed by substrate addition measured after 10 mins in presence of NADPH by microplate reader analysis relative to control Homo sapiens 50.0 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 37.35 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 11.91 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 4.452 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.77 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.37 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.09 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.77 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.37 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.09 %
Inhibition of porcine pancreatic lipase at 5 ug/ml using 4-MU oleate as substrate incubated for 30 min by fluorescence method relative to control Sus scrofa 96.0 %
Inhibition of PTL (unknown origin) at 50 uM relative to control Homo sapiens 89.5 %
Inhibition of PTL (unknown origin) Homo sapiens 780.0 nM
Inhibition of PTL in human SW1990 cell lysate at 50 uM by Western blot analysis relative to control Homo sapiens 50.0 %
Inhibition of Lipase (unknown origin) Homo sapiens 10.0 nM
Inhibition of pig pancreatic lipase type 2 using p-nitrophenyl butyrate as substrate preincubated with enzyme for 10 mins followed by susbtrate addition and measured after 30 mins by spectrophotometric analysis Sus scrofa 600.0 nM

Cross References

Resources Reference
ChEBI 94686
ChEMBL CHEMBL175247
DrugBank DB01083
DrugCentral 1996
FDA SRS 95M8R751W8
Human Metabolome Database HMDB0015215
Guide to Pharmacology 5277
KEGG D04028
PharmGKB PA164776864
PubChem 3034010
SureChEMBL SCHEMBL16408
ZINC ZINC000008214635
CONTENTS