ASIMADOLINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H30N2O2
Molecular Weight	414.5393
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN([C@H](CN1CC[C@H](O)C1)C2=CC=CC=C2)C(=O)C(C3=CC=CC=C3)C4=CC=CC=C4

InChI

InChIKey=JHLHNYVMZCADTC-LOSJGSFVSA-N

InChI=1S/C27H30N2O2/c1-28(25(21-11-5-2-6-12-21)20-29-18-17-24(30)19-29)27(31)26(22-13-7-3-8-14-22)23-15-9-4-10-16-23/h2-16,24-26,30H,17-20H2,1H3/t24-,25+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346361
Curator's Comment: description was created based on several sources, including: http://www.tiogapharma.com/Drug-Development/index.html https://www.ncbi.nlm.nih.gov/pubmed/20809870 https://www.wikigenes.org/e/chem/e/179340.html

Asimadoline is an orally active, highly selective kappa-opioid receptor agonist with approximately 500-fold greater affinity for human kappa-, as compared with either delta- or mu-opioid receptors. Due to its high selectivity for the kappa-opioid receptor, asimadoline does not produce mu-opioid like side effects. It is investigated for use/treatment in irritable bowel syndrome, pruritus, postoperative ileus. A drug interaction study investigating the coadministration of asimadoline with ketoconazole was performed in healthy volunteers - a two to three-fold increase in AUC and Cmax of asimadoline was observed with concomitant administration of ketoconazole. The most common adverse events are diarrhea, nausea, sinusitis, headache and fatigue.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Kappa opioid receptor 108 Target ID: CHEMBL237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346361 \| https://www.ncbi.nlm.nih.gov/pubmed/7889287	Agonist 2678	1.2 nM [IC50]
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346361	Agonist 2678	601.0 nM [IC50]
Delta opioid receptor 77 Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22346361	Agonist 2678	597.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Irritable bowel syndrome 60 Sources: http://adisinsight.springer.com/drugs/800005880	Primary	Phase III 656	Unknown Approved Use Unknown
Pruritus associated with atopic dermatitis 2 Sources: http://www.tiogapharma.com/Press/index.html http://en.pharmacodia.com/web/drug/1_554.html	Primary	Phase II 1132	Unknown Approved Use Unknown
Postoperative ileus 7 Sources: http://adisinsight.springer.com/drugs/800005880	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
213.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
90.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1205.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
375.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
58.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
10.57 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.55 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10971307/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	ASIMADOLINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% REVIEW https://pubmed.ncbi.nlm.nih.gov/20809870/			ASIMADOLINE serum	Homo sapiens

Doses

Dose	Population	Adverse events
0.15 mg 2 times / day multiple, oral (unknown) Dose: 0.15 mg, 2 times / day Route: oral Route: multiple Dose: 0.15 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 146 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 146 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	Disc. AE: Diarrhoea, Diarrhoea... AEs leading to discontinuation/dose reduction: Diarrhoea (3.4%) Diarrhoea (3.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	Disc. AE: vomiting, nausea... AEs leading to discontinuation/dose reduction: vomiting (2.6%) nausea (2.6%) vomiting (2.6%) nausea (2.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	Disc. AE: diarrhoea, diarrhoea... AEs leading to discontinuation/dose reduction: diarrhoea (2.1%) diarrhoea (2.1%) abdominal pain (2.1%) abdominal pain (2.1%) vomiting (0.7%) vomiting (0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/18466359

AEs

AE	Significance	Dose	Population
Diarrhoea	3.4% Disc. AE	0.15 mg 2 times / day multiple, oral (unknown) Dose: 0.15 mg, 2 times / day Route: oral Route: multiple Dose: 0.15 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 146 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 146 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
Diarrhoea	3.4% Disc. AE	0.15 mg 2 times / day multiple, oral (unknown) Dose: 0.15 mg, 2 times / day Route: oral Route: multiple Dose: 0.15 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 146 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 146 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
nausea	2.6% Disc. AE	0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
nausea	2.6% Disc. AE	0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
vomiting	2.6% Disc. AE	0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
vomiting	2.6% Disc. AE	0.5 mg 2 times / day multiple, oral (unknown) Dose: 0.5 mg, 2 times / day Route: oral Route: multiple Dose: 0.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy, ADULT n = 148 Health Status: unhealthy Condition: irritable bowel syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 148 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
vomiting	0.7% Disc. AE	1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
vomiting	0.7% Disc. AE	1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
abdominal pain	2.1% Disc. AE	1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
abdominal pain	2.1% Disc. AE	1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
diarrhoea	2.1% Disc. AE	1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359
diarrhoea	2.1% Disc. AE	1 mg 2 times / day multiple, oral (unknown) Dose: 1 mg, 2 times / day Route: oral Route: multiple Dose: 1 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18466359	unhealthy n = 142 Health Status: unhealthy Condition: irritable bowel syndrome Sex: M+F Food Status: UNKNOWN Population Size: 142 Sources: https://pubmed.ncbi.nlm.nih.gov/18466359

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00APZ5	https://www.1pchem.com/search?query=1P00APZ5
AChemBlock	O33791	http://www.achemblock.com/catalogsearch/result/?q=O33791
AK Scientific	SYN5543	https://aksci.com/item_detail.php?cat=SYN5543
AstaTech	42165	http://astatechinc.com/CPSResult.php?CRNO=42165
BOC Sciences	153205-46-0	http://www.bocsci.com/description.asp?cas=153205-46-0
Chem Scene	CS-8053	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-8053
KeyOrganics	AS-16871	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16871
MedChem Express	HY-107384	https://www.medchemexpress.com/search.html?q=HY-107384&ft=&fa=&fp=
MolPort	MolPort-006-170-057	https://www.molport.com/shop/molecule-link/MolPort-006-170-057
MolPort	MolPort-046-594-298	https://www.molport.com/shop/molecule-link/MolPort-046-594-298
Molnova	M17397	https://www.molnova.com/en/serch-list.html?keywords=M17397
Molnova	M18069	https://www.molnova.com/en/serch-list.html?keywords=M18069
MuseChem	M101359	https://www.musechem.com/product/M101359.html
MuseChem	R024641	https://www.musechem.com/product/R024641.html
ShangHai Biochempartner	BCP001500	http://www.biochempartner.com/search_BCP001500
TargetMol	T4691	https://www.targetmol.com/search?keyword=T4691
Tetrahedron	TS69713	http://www.thsci.com/search.do?q=TS69713
Toronto Research Chemicals	A788250	https://www.trc-canada.com/product-detail/?CatNum=A788250
eMolecules	271447542	https://orderbb.emolecules.com/search/#?query=271447542
eMolecules	56972795	https://orderbb.emolecules.com/search/#?query=56972795
eMolecules	76746732	https://orderbb.emolecules.com/search/#?query=76746732
mcule	MCULE-2775654388	https://mcule.com/MCULE-2775654388/
mcule	MCULE-3808088772	https://mcule.com/MCULE-3808088772/
mcule	MCULE-8423420432	https://mcule.com/MCULE-8423420432/

PubMed

Title	Date	PubMed
The kappa-opioid agonist, asimadoline, alters cytokine gene expression in adjuvant arthritis.	2001 Sep	11561112
CJ-15,208, a novel kappa opioid receptor antagonist from a fungus, Ctenomyces serratus ATCC15502.	2002 Oct	12523817
Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans.	2003 Apr	12631557
Functional dyspepsia: drugs for new (and old) therapeutic targets.	2004 Aug	15324710
Gateways to clinical trials.	2004 Mar	15071612
Endogenous opioid analgesia in peripheral tissues and the clinical implications for pain control.	2005 Dec	18360571
Peripheral opioids for functional GI disease: a reappraisal.	2006	16699267
Gateways to clinical trials.	2007 Nov	18193114
Efficacy of on-demand asimadoline, a peripheral kappa-opioid agonist, in females with irritable bowel syndrome.	2007 Nov	17900994
Opioid-induced bowel dysfunction.	2008 Feb	21063859
Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome.	2008 Jul	18466359
Asimadoline, a kappa-opioid agonist, and satiation in functional dyspepsia.	2008 Jun 1	18331462
Involvement of kappa-opioid receptors in visceral nociception in mice.	2008 Oct	18643891
Novel pharmacology: asimadoline, a kappa-opioid agonist, and visceral sensation.	2008 Sep	18715494
SA14867, a newly synthesized kappa-opioid receptor agonist with antinociceptive and antipruritic effects.	2010 Nov 25	20813108
Asimadoline in the treatment of irritable bowel syndrome.	2010 Oct	20809870

Patents

Sample Use Guides

In Vivo Use Guide

0.5 mg and placebo were administered twice daily for up to 12 weeks.

Route of Administration: Oral

In Vitro Use Guide

The cell lines (LLC-PK1, L-mdr1a, L-mdr1b and L-MDR1) were grown to confluent polarized monolayers on porous membrane filters, and polarized trans-epithelial transport of [14C]-asimadoline (10 μm) was determined. Asimadoline is well transported in vitro by mouse mdr1a P-gp and also by human MDR1 P-gp but not efficiently by mouse mdr1b P-gp.

Name

Type

Language

ASIMADOLINE

Official Name

English

asimadoline [INN]

Common Name

English

ASIMADOLINE [MI]

Common Name

English

N-((.ALPHA.S)-.ALPHA.-(((3S)-3-HYDROXY-1-PYRROLIDINYL)METHYL)BENZYL)-N-METHYL-2,2-DIPHENYLACETAMIDE

Common Name

English

EMD-61753

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C241