LORCASERIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H14ClN
Molecular Weight	195.689
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

C[C@H]1CNCCC2=C1C=C(Cl)C=C2

InChI

InChIKey=XTTZERNUQAFMOF-QMMMGPOBSA-N

InChI=1S/C11H14ClN/c1-8-7-13-5-4-9-2-3-10(12)6-11(8)9/h2-3,6,8,13H,4-5,7H2,1H3/t8-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C11H14ClN
Molecular Weight	195.689
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Lorcaserin, currently marketed under the trade name Belviq and previously Lorqess during development, is a weight-loss drug developed by Arena Pharmaceuticals. Lorcaserin is a selective 5-HT2C receptor agonist, and in vitro testing of the drug showed reasonable selectivity for 5-HT2C over other related targets. 5-HT2C receptors are located almost exclusively in the brain, and can be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus. The activation of 5-HT2C receptors in the hypothalamus is supposed to activate proopiomelanocortin (POMC) production and consequently promote weight loss through satiety. This hypothesis is supported by clinical trials and other studies. While it is generally thought that 5-HT2C receptors help to regulate appetite as well as mood, and endocrine secretion, the exact mechanism of appetite regulation is not yet known. Lorcaserin has shown 100x selectivity for 5-HT2C versus the closely related 5-HT2B receptor, and 17x selectivity over the 5-HT2A receptor

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 2c (5-HT2c) receptor 124	Agonist 2,678		15.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203	Curative		Approved 8,429	Belviq

C_max

Value	Dose	Analyte	Population
38.5 ng/mL	20 mg single, oral	LORCASERIN plasma	Homo sapiens
56.1 ng/mL	20 mg single, oral	LORCASERIN plasma	Homo sapiens
69.5 ng/mL	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
78.7 ng/mL	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
11.16 ng/mL	3 mg single, oral	LORCASERIN plasma	Homo sapiens
13.7 ng/mL	3 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
39.7 ng/mL	10 mg single, oral	LORCASERIN plasma	Homo sapiens
50.85 ng/mL	10 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
83.77 ng/mL	20 mg single, oral	LORCASERIN plasma	Homo sapiens
85.02 ng/mL	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
611 ng × h/mL	20 mg single, oral	LORCASERIN plasma	Homo sapiens
808 ng × h/mL	20 mg single, oral	LORCASERIN plasma	Homo sapiens
1216 ng × h/mL	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
1318 ng × h/mL	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
172 ng × h/mL	3 mg single, oral	LORCASERIN plasma	Homo sapiens
172.2 ng × h/mL	3 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
516.9 ng × h/mL	10 mg single, oral	LORCASERIN plasma	Homo sapiens
593.8 ng × h/mL	10 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
1086.2 ng × h/mL	20 mg single, oral	LORCASERIN plasma	Homo sapiens
899.2 ng × h/mL	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
13 h	20 mg single, oral	LORCASERIN plasma	Homo sapiens
12.4 h	20 mg single, oral	LORCASERIN plasma	Homo sapiens
12.4 h	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
12 h	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
11.38 h	3 mg single, oral	LORCASERIN plasma	Homo sapiens
10.23 h	3 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
8.87 h	10 mg single, oral	LORCASERIN plasma	Homo sapiens
10.28 h	10 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
9.55 h	20 mg single, oral	LORCASERIN plasma	Homo sapiens
11.26 h	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens

F_unbound

Value	Dose	Analyte	Population
30%	3 mg single, oral	LORCASERIN plasma	Homo sapiens
30%	3 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
30%	10 mg single, oral	LORCASERIN plasma	Homo sapiens
30%	10 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens
30%	20 mg single, oral	LORCASERIN plasma	Homo sapiens
30%	20 mg 1 times / day steady-state, oral	LORCASERIN plasma	Homo sapiens

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:65353	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:65353
ChemicalBook	CB61011744	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB61011744
ZINC	ZINC000006733300	http://zinc15.docking.org/substances/ZINC000006733300

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PubMed

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Title	Date	PubMed
Nonincretin drugs in later-stage development.	2014 Jan	25618226
Drug safety evaluation of naltrexone/bupropion for the treatment of obesity.	2014 Jun	24766397
[Cutting-edge of medicine; the prospects of novel anti-obesity drugs].	2014 Mar 10	24796150

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Patents

Sample Use Guides

In Vivo Use Guide

One tablet of 10 mg twice daily

Route of Administration: Oral

In Vitro Use Guide

Lorcaserin was evaluated for its ability to inhibit neurotransmitter uptake into rat brain synaptosomes. Lorcaserin weakly inhibited norepinephrine (EC50 = 2500 nM), serotonin (EC50 = 1400 nM), and dopamine (EC50 = 12,000 nM) uptake.

Substance Class	Chemical
Record UNII	637E494O0Z
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

LORCASERIN

Official Name

English

LORCASERIN [MI]

Common Name

English

lorcaserin [INN]

Common Name

English

LORCASERIN [VANDF]

Common Name

English

(1R)-8-CHLORO-1-METHYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINE

Systematic Name

English

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Classification Tree

Code System

Code

Designated

FDA ORPHAN DRUG

828021

Centrally acting antiobesity products

WHO-ATC

A08AA11

Designated

FDA ORPHAN DRUG

758920

Obesity

LIVERTOX

NBK548834

Agent Affecting Nervous System

NCI_THESAURUS

C47794

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Code System

Code

Type

Description

DAILYMED

637E494O0Z

PRIMARY

NDF-RT

N0000185009

PRIMARY

Serotonin 2c Receptor Agonists [MoA]

ChEMBL

CHEMBL360328

PRIMARY

HSDB

8128

PRIMARY

MESH

C506658

PRIMARY

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Related Record

Type

Details


					W80H4WI8LW

URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 2B17

METABOLIC ENZYME -> SUBSTRATE

Amount:


					081I12ZA58

CYTOCHROME P450 2C19

METABOLIC ENZYME -> SUBSTRATE

Amount:


					W4BO00H6K6

5-HYDROXYTRYPTAMINE RECEPTOR 2C

TARGET -> AGONIST

Qualification:

Ki

Amount:

13 NANOMOLAR (average)


					VK4SQL11C0

CYTOCHROME P450 1A2

METABOLIC ENZYME -> SUBSTRATE

Amount:


					3318TFY23Q

URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9

METABOLIC ENZYME -> SUBSTRATE

Amount:

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Related Record

Type

Details


					8HFX2F4DWV

(2S,3S,4S,5R)-6-(((5R)-7-CHLORO-5-METHYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-1-YL)OXY)-3,4,5-TRIHYDROXY-TETRAHYDROPYRAN-2-CARBOXYLIC ACID

METABOLITE -> PARENT

Qualification:

URINE

Amount:

PERCENTAGE OF DOSE EXCRETED 1.3 % (average)


					TB5N3D6KCE

(2S,3S,4S,5R)-6-(((5R)-7-CHLORO-5-METHYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-8-YL)OXY)-3,4,5-TRIHYDROXY-TETRAHYDROPYRAN-2-CARBOXYLIC ACID

METABOLITE -> PARENT

Qualification:

URINE

Amount:

PERCENTAGE OF DOSE EXCRETED 3 % (average)


					RDJ125V8OM

1-HYDROXY LORCASERIN

METABOLITE INACTIVE -> PARENT

Interaction Type:

MINOR

Qualification:

URINE

Amount:


					WR2F7EU9VN

(2S,3S,4S,5R)-6-(((5R)-7-CHLORO-5-METHYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-6-YL)OXY)-3,4,5-TRIHYDROXY-TETRAHYDROPYRAN-2-CARBOXYLIC ACID

METABOLITE -> PARENT

Qualification:

URINE

Amount:

PERCENTAGE OF DOSE EXCRETED 2.2 % (average)


					D94D8M36Y4

(2S,3S,4S,5R)-6-(((5R)-7-CHLORO-5-METHYL-2-OXO-4,5-DIHYDRO-1H-3-BENZAZEPIN-3-YL)OXY)-3,4,5-TRIHYDROXY-TETRAHYDROPYRAN-2-CARBOXYLIC ACID

METABOLITE -> PARENT

Comments:

M8 (1-carboxyl glucuronide) was excreted in urine greater than 10% of dose, but it was a minor metabolite in plasma.

Qualification:

URINE

Amount:

PERCENTAGE OF DOSE EXCRETED 12.2 % (average)

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Related Record

Type

Details


					637E494O0Z

LORCASERIN

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Parameters
Biological Half-life	PHARMACOKINETIC	11 hours [10.16 to 11.2] (average)	Single Dose Administration [10 to 40] mg (average)

Tmax	PHARMACOKINETIC	[1.75 to 2.25] hours (average)	Single Dose Administration [10 to 40] mg (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound