CIPARGAMIN

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H14Cl2FN3O
Molecular Weight	390.238
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CC2=C(NC3=C2C=C(F)C(Cl)=C3)[C@@]4(N1)C(=O)NC5=C4C=C(Cl)C=C5

InChI

InChIKey=CKLPLPZSUQEDRT-WPCRTTGESA-N

InChI=1S/C19H14Cl2FN3O/c1-8-4-11-10-6-14(22)13(21)7-16(10)23-17(11)19(25-8)12-5-9(20)2-3-15(12)24-18(19)26/h2-3,5-8,23,25H,4H2,1H3,(H,24,26)/t8-,19+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25075833 | https://www.novartis.com/sites/www.novartis.com/files/novartis-pipeline-2015-annual-report.pdf | https://newdrugapprovals.org/tag/cipargamin/

Cipargamin is an experimental synthetic antimalarial molecule belonging to the spiroindolone class. It possesses both the potency (average IC50 of 550 pM against asexual blood-stage P. falciparum) and favorable pharmacokinetics (elimination half-life of ~24 hours in humans) needed for a single-dose cure, a feature that could help slow the onset of parasite resistance and that is not shared by existing, approved antimalarial drugs. KAE609 is also unique in its ability to block transmission to mosquitoes. Cipargamin is a parasite P-type ATPase4 inhibitor. Cipargamin in phase II clinical trials for the treatment of acute, uncomplicated malaria due to plasmodium falciparum monoinfection. Nausea was the most common reported adverse effect. The adverse events were generally mild and did not lead to any discontinuations of the drug.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
non-SERCA-type Ca2+ -transporting P-ATPase 1 Target ID: 811171.0 Gene Symbol: ATPase4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25322084 \| https://www.ncbi.nlm.nih.gov/pubmed/27291296 \| https://www.novartis.com/sites/www.novartis.com/files/novartis-pipeline-2015-annual-report.pdf	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 96 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25075833	Curative		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
161 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1170 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
991 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
468 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1770 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1.91 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.42 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
29.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
21.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
23.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	100 mg 1 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25114127	150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CIPARGAMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P000J2Y	https://www.1pchem.com/search?query=1P000J2Y
AChemBlock	L14954	http://www.achemblock.com/catalogsearch/result/?q=L14954
AK Scientific	3828AL	https://aksci.com/item_detail.php?cat=3828AL
Angene	AGN-PC-0PD6LA	http://www.angenechemical.com/productshow/AGN-PC-0PD6LA.html
AstaTech	P14044	http://astatechinc.com/CPSResult.php?CRNO=P14044
BLD Pharm	BD333330	http://www.bldpharm.com/search/Search.html?keyword=BD333330
Chem Scene	CS-7486	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-7486
ChemShuttle	171494	https://www.chemshuttle.com/catalogsearch/result/?q=171494
Combi-Blocks	QM-8772	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-8772
eMolecules	271379001	https://orderbb.emolecules.com/search/#?query=271379001
eMolecules	302085582	https://orderbb.emolecules.com/search/#?query=302085582
eMolecules	56973801	https://orderbb.emolecules.com/search/#?query=56973801
KeyOrganics	AS-51977	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-51977
Lab Network	LN01346348	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01346348
mcule	MCULE-6730826688	https://mcule.com/MCULE-6730826688/
MedChem Express	HY-14430	https://www.medchemexpress.com/search.html?q=HY-14430&ft=&fa=&fp=
Molnova	M10671	https://www.molnova.com/en/serch-list.html?keywords=M10671
MolPort	MolPort-039-337-269	https://www.molport.com/shop/molecule-link/MolPort-039-337-269

PubMed

Title	Date	PubMed
A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel antimalarial Spiroindolone KAE609 (Cipargamin) to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers.	2014-10	25114127
Spiroindolone KAE609 for falciparum and vivax malaria.	2014-07-31	25075833
Spiroindolone that inhibits PfATPase4 is a potent, cidal inhibitor of Toxoplasma gondii tachyzoites in vitro and in vivo.	2014	24366743
Mechanistic study of the spiroindolones: a new class of antimalarials.	2012-08-24	22922283
The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.	2012-07	22508309

Patents

Sample Use Guides

In Vivo Use Guide

30 mg once a day for three days

Route of Administration: Oral

In Vitro Use Guide

Cipargamin was found to inhibit the early and late development of Plasmodium falciparum gametocytes in vitro in a dose-dependent fashion over a range of 5 to 500 nM.

Name

Type

Language

CIPARGAMIN

Official Name

English

KAE-609

Preferred Name

English

Cipargamin [WHO-DD]

Common Name

English

SPIRO(3H-INDOLE-3,1'-(1H)PYRIDO(3,4-B)INDOL)-2(1H)-ONE, 5,7'-DICHLORO-6'-FLUORO-2',3',4',9'-TETRAHYDRO-3'-METHYL-, (1'R,3'S)-

Systematic Name

English

NITD-609

Code

English

KAE609

Code

English

NITD-609, (+)-

Code

English

cipargamin [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

746820