CAMICINAL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H33FN4O
Molecular Weight	424.5541
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CN(CC2=CC=C(CC(=O)N3CCC(CC3)NC4=CC=CC(F)=C4)C=C2)CCN1

InChI

InChIKey=RZKDEGZIFSJVNA-IBGZPJMESA-N

InChI=1S/C25H33FN4O/c1-19-17-29(14-11-27-19)18-21-7-5-20(6-8-21)15-25(31)30-12-9-23(10-13-30)28-24-4-2-3-22(26)16-24/h2-8,16,19,23,27-28H,9-15,17-18H2,1H3/t19-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19374732
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25341626 http://adisinsight.springer.com/drugs/800028309

GlaxoSmithKline is developing Camicinal (GSK 962040), an oral motilin receptor agonist for the treatment of gastroparesis. Camicinal is being evaluated in phase II for diabetic gastroparesis and gastroparesis. Camicinal is well tolerated in multiple trials with no serious drug-related adverse events or changes in ECG chemistry when given as a single oral dose of up to 125 mg. Although larger studies are soon to be reported, current evidence shows that adverse events occurred evenly between the placebo and treatment groups, and was generally mild. Camicinal has been previously shown to increase gastric emptying in volunteers after repeat dosing over 14 days with no tolerance effect in patients with gastroparesis and type 1 diabetes. Camicinal meets the criteria of an ideal motilin agonist. The compound activates long-lasting cholinergic contractility at low doses in the antrum with greater efficacy than current therapeutic options.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Motilin receptor 3 Target ID: CHEMBL2203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19374732	Agonist 2678		7.9 null [pEC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gastroparesis 9 Sources: https://clinicaltrials.gov/ct2/show/NCT02210000	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1124.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26924243	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	CAMICINAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
288.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26924243	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	CAMICINAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
488 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26924243	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	CAMICINAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
16774.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26924243	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	CAMICINAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4103.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26924243	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	CAMICINAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6193.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26924243	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	CAMICINAL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 P-gp 1461 CYP2C19 1478

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678098	inconclusive [IC50 14.581 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19191554/	no [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19191554/	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19191554/	no [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19191554/	weak [IC50 34 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19191554/	yes [IC50 26 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/19374732/

Sourcing

Vendor/Aggregator	ID	URL
AbovChem LLC	HY-10922A	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-10922A
ApexBio Technology	B1137	https://www.apexbt.com/catalogsearch/result/?q=B1137
ApexBio Technology	B1149	https://www.apexbt.com/catalogsearch/result/?q=B1149
BLD Pharm	BD631015	http://www.bldpharm.com/search/Search.html?keyword=BD631015
BLD Pharm	BD631016	http://www.bldpharm.com/search/Search.html?keyword=BD631016
Chem Scene	CS-2312	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2312
MedChem Express	HY-10922	https://www.medchemexpress.com/search.html?q=HY-10922&ft=&fa=&fp=
MolPort	MolPort-046-416-872	https://www.molport.com/shop/molecule-link/MolPort-046-416-872
Molnova	M16615	https://www.molnova.com/en/serch-list.html?keywords=M16615
Molnova	M16616	https://www.molnova.com/en/serch-list.html?keywords=M16616
MuseChem	I005448	https://www.musechem.com/product/I005448.html
eMolecules	275114546	https://orderbb.emolecules.com/search/#?query=275114546
eMolecules	301190100	https://orderbb.emolecules.com/search/#?query=301190100
eMolecules	301190356	https://orderbb.emolecules.com/search/#?query=301190356
eMolecules	50283019	https://orderbb.emolecules.com/search/#?query=50283019
eMolecules	50285375	https://orderbb.emolecules.com/search/#?query=50285375
mcule	MCULE-5490027140	https://mcule.com/MCULE-5490027140/
mcule	MCULE-6309533437	https://mcule.com/MCULE-6309533437/

PubMed

Title	Date	PubMed
Discovery of N-(3-fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-piperidinamine (GSK962040), the first small molecule motilin receptor agonist clinical candidate.	2009 Feb 26	19191554
GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility.	2009 Jun	19374732
Gastrointestinal hormones and gut motility.	2015 Feb	25517024
The investigational drug camicinal for the treatment of gastroparesis.	2015 Jan	25341626

Patents

Sample Use Guides

In Vivo Use Guide

25 mg tablet to be taken orally with 100mL of water in the morning

Route of Administration: Oral

In Vitro Use Guide

In rabbit gastric antrum, Camicinal (GSK962040) 300 nmol/L-10 umol/L caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 +/- 47% at 3 umol/L.

Name

Type

Language

CAMICINAL

Official Name

English

GSK962040B

Code

English

1-(4-((3-FLUOROPHENYL)AMINO)PIPERIDIN-1-YL)-2-(4-(((3S)-3-METHYLPIPERAZIN-1-YL)METHYL)PHENYL)ETHAN-1-ONE

Systematic Name

English

CAMICINAL [USAN]

Common Name

English

GSK-962040

Code

English

Camicinal [WHO-DD]

Common Name

English

GSK-962040B

Code

English

camicinal [INN]

Common Name

English

GSK962040

Code

English

Code System Code Type Description

DRUG BANK

DB12567