SENICAPOC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H15F2NO
Molecular Weight	323.336
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)C(C1=CC=CC=C1)(C2=CC=C(F)C=C2)C3=CC=C(F)C=C3

InChI

InChIKey=SCTZUZTYRMOMKT-UHFFFAOYSA-N

InChI=1S/C20H15F2NO/c21-17-10-6-15(7-11-17)20(19(23)24,14-4-2-1-3-5-14)16-8-12-18(22)13-9-16/h1-13H,(H2,23,24)

HIDE SMILES / InChI

Molecular Formula	C20H15F2NO
Molecular Weight	323.336
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12433690 | https://www.ncbi.nlm.nih.gov/pubmed/19236269 | http://adisinsight.springer.com/drugs/800013404 | https://www.ncbi.nlm.nih.gov/pubmed/28060543 | https://www.ncbi.nlm.nih.gov/pubmed/28694658 | https://www.ncbi.nlm.nih.gov/pubmed/28364331

Senicapoc (ICA-17043) is a blocker of Gardos channel, a calcium-activated potassium channel, in the red blood cell. Preclinical studies and studies in transgenic models of Sickle cell disease (SCD) show that inhibition of potassium efflux through the Gardos channel is associated with an increased haemoglobin level, decreased dense cells and decreased hemolysis. Senicapoc is well tolerated when administered to SCD patients and produces dose-dependent increases in hemoglobin and decreases in markers of hemolysis. Senicapoc exerts anti-fibrotic and anti-inflammatory activities. Senicapoc has previously been in Phase III and Phase II clinical trials for the treatment of SCD and asthma, respectively.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Intermediate conductance calcium-activated potassium channel protein 4 10 Target ID: CHEMBL4305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12433690	Blocker 537		11.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Sickle cell disease 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19236269	Primary	Phase III 656	Unknown Approved Use Unknown
Asthma 241 Sources: http://adisinsight.springer.com/drugs/800013404 https://www.ncbi.nlm.nih.gov/pubmed/23826167	Primary	Phase II 1132	Unknown Approved Use Unknown
Hereditary xerocytosis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28295477 https://www.ncbi.nlm.nih.gov/pubmed/27443288	Primary	Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
108.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
109.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
59.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
19696.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
30675.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11826 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
219.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
296.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
369.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064199	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	SENICAPOC plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYPs 22

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18232633/	no [Inhibition 10 uM]
CYPs 28	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16981849/	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/28694658/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P002VHC	https://www.1pchem.com/search?query=1P002VHC
A2B Chem	AB33312	http://a2bchem.com/prod/AB33312
AK Scientific	Y5374	https://aksci.com/item_detail.php?cat=Y5374
Achemo Scientific Limited	AC-33385	http://www.achemo.com/search/?Keyword=AC-33385
Ambeed	A239412	http://www.ambeed.com/search/Search.html?keyword=A239412
Angene	AGN-PC-0R4Q35	http://www.angenechemical.com/productshow/AGN-PC-0R4Q35.html
AstaTech	C74487	http://astatechinc.com/CPSResult.php?CRNO=C74487
BLD Pharm	BD165423	http://www.bldpharm.com/search/Search.html?keyword=BD165423
BOC Sciences	289656-45-7	http://www.bocsci.com/description.asp?cas=289656-45-7
Capot Chemical	19381	https://www.capotchem.com/search.do?q=19381
Chem Scene	CS-0294	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0294
Debye Scientific	DB-003217	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-003217
Hairui	HR110372	http://www.hairuichem.com/en/product/search.do?q=HR110372
KeyOrganics	MS-20434	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=MS-20434
Lab Network	LN00191149	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00191149
Matrix Scientific	94238	http://www.matrixscientific.com/094238.html
MedChem Express	HY-50694	https://www.medchemexpress.com/search.html?q=HY-50694&ft=&fa=&fp=
MolPort	MolPort-019-996-128	https://www.molport.com/shop/molecule-link/MolPort-019-996-128
Molnova	M13889	https://www.molnova.com/en/serch-list.html?keywords=M13889
MuseChem	I002999	https://www.musechem.com/product/I002999.html
ShangHai Biochempartner	BCP14507	http://www.biochempartner.com/search_BCP14507
TargetMol	T3528	https://www.targetmol.com/search?keyword=T3528
Wonderchem	WD05SZ3	http://www.wonder-chem.com/search.html?text=WD05SZ3
eMolecules	43451060	https://orderbb.emolecules.com/search/#?query=43451060
eNovation Chemicals	D552124	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D552124&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1853417684	https://mcule.com/MCULE-1853417684/

PubMed

Title	Date	PubMed
ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice.	2003 Mar 15	12433690
Investigational agents for sickle cell disease.	2006 Aug	16859388
Dose-escalation study of ICA-17043 in patients with sickle cell disease.	2006 Nov	17064199
[Clinical trials of new therapeutic pharmacology for sickle cell disease].	2006 Oct-Dec	17446160
Gardos pathway to sickle cell therapies?	2008 Apr 15	18434967
Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia.	2008 Apr 15	18192510
Novel inhibitors of the Gardos channel for the treatment of sickle cell disease.	2008 Feb 28	18232633
Pathophisiology of sickle cell disease and new drugs for the treatment.	2009 Dec 20	21415994
Senicapoc (ICA-17043): a potential therapy for the prevention and treatment of hemolysis-associated complications in sickle cell anemia.	2009 Feb	19236269
Promising therapies in sickle cell disease.	2009 Mar	19275572
Hypoxia activates a Ca2+-permeable cation conductance sensitive to carbon monoxide and to GsMTx-4 in human and mouse sickle erythrocytes.	2010 Jan 15	20090940

Patents

Sample Use Guides

In Vivo Use Guide

Patients with sickle cell disease received single doses of ICA-17043 (Senicapoc) -50 mg, 100 mg, and 150 mg. The mean area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) for ICA-17043 increased in a dose-related manner (11,827, 19,697, and 30,676 ng.hr/ml for 50, 100, and 150 mg, respectively). Overall mean half-life was 12.8 days. Mean peak plasma concentrations rose between the 50- and 100-mg dose levels but plateaued at 150 mg (59.1, 108.7, and 109.1 ng/ml, respectively).

Route of Administration: Oral

In Vitro Use Guide

Senicapoc (ICA-17043) inhibited red blood cells dehydration with an IC(50) of 30 +/- 20 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:54:45 GMT 2023` Edited by `admin` on `Fri Dec 15 15:54:45 GMT 2023`
Record UNII	TS6G201A6Q
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SENICAPOC

Official Name

English

PF-05416266

Code

English

ICA-17043

Code

English

2,2-Bis(4-fluorophenyl)-2-phenylacetamide

Systematic Name

English

senicapoc [INN]

Common Name

English

SENICAPOC [MART.]

Common Name

English

Senicapoc [WHO-DD]

Common Name

English

SENICAPOC [USAN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

131999