FABESETRON

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H19N3O
Molecular Weight	293.363
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(C[C@H]2CCC3=C(C)C4=C(C=CC=C4)N3C2=O)N=CN1

InChI

InChIKey=AEKQMJRJRAHOAP-CYBMUJFWSA-N

InChI=1S/C18H19N3O/c1-11-14-5-3-4-6-17(14)21-16(11)8-7-13(18(21)22)9-15-12(2)19-10-20-15/h3-6,10,13H,7-9H2,1-2H3,(H,19,20)/t13-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/8496821
Curator's Comment: description was created based on several sources, including, http://www.ncbi.nlm.nih.gov/pubmed/16079468

Fabesetron is a dual 5HT3 and 5HT4 receptors antagonist that was developed in Japan for the treatment of chemotherapy-induced emesis and gastrointestinal disorders. The development of the drug was terminated in phase II.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
5-hydroxytryptamine receptor 4 8 Target ID: Q13639\|\|\|Q9NY73 Gene ID: 3360.0 Gene Symbol: HTR4 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/8496821	Antagonist 2849
5-hydroxytryptamine receptor 3A 7 Target ID: P46098 Gene ID: 3359.0 Gene Symbol: HTR3A Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/8496821	Antagonist 2849		8.84 null [pIC50]

Conditions

Condition	Modality	Highest Phase	Product
Vomiting 38 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16079468	Secondary	Phase II 1147	Unknown Approved Use Unknown
Gastrointestinal disorders 94 Sources: http://www.ncbi.nlm.nih.gov/pubmed/8331576	Primary	Phase II 1147	Unknown Approved Use Unknown
Nausea 63 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16079468	Secondary	Phase II 1147	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Antiemetic activity of FK1052, a 5-HT3- and 5-HT4-receptor antagonist, in Suncus murinus and ferrets.	2005-08	16079468
Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans.	2001-10	11560875
Probable involvement of the 5-hydroxytryptamine(4) receptor in methotrexate-induced delayed emesis in dogs.	2000-03	10688616
Combined blockade of 5-HT3- and 5-HT4-serotonin receptors inhibits colonic functions in conscious rats and mice.	1997-04	9103508
New 5-HT3 (serotonin-3) receptor antagonists. III. An efficient synthesis of carbon 14-labeled (+)-8,9-dihydro-10-methyl-7-[(5-methyl-1H-imidazol-4- yl)methyl]pyrido[1,2-a]indol-6(7H)-one hydrochloride (FK 1052).	1995-08	7553979
New 5-HT3 (serotonin-3) receptor antagonists. I. Synthesis and structure-activity relationships of pyrido[1,2-a]indoles.	1994-12	7697771
New 5-HT3 (serotonin-3) receptor antagonists, II. Synthesis and structure-activity relationships of pyrimido[1,6-a]indoles.	1994-12	7697772
Effect of FK1052, a potent 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptor dual antagonist, on colonic function in vivo.	1993-07	8331576
Pharmacological characterization of FK1052, a dihydropyridoindole derivative, as a new serotonin 3 and 4 dual receptor antagonist.	1993-05	8496821

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

The effect of fabesteron on short-circuit current was investigated using submucosa-mucosa sheets of guinea-pig distal colon. The drug at 10(-9) M suppressed the 5-HT-evoked response to 69% of control.

Name

Type

Language

fabesetron [INN]

Preferred Name

English

FABESETRON

Official Name

English

(+)-(R)-8,9-DIHYDRO-10-METHYL-7-((5-METHYLIMIDAZOL-4-YL)METHYL)PYRIDO(1,2-A)INDOL-6(7H)-ONE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C94726