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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 of CIPARGAMIN

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

Molecular Formula C19H14Cl2FN3O
Molecular Weight 390.238
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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

Curator's Comment: # Novartis

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
161 ng/mL
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
991 ng/mL
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
1170 ng/mL
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
1770 ng/mL
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
468 ng/mL
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1.91 μg × h/mL
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
14.1 μg × h/mL
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
19.8 μg × h/mL
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
29.4 μg × h/mL
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
6.42 μg × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.4 h
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
28 h
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
23.1 h
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
26.9 h
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
22.4 h
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
PubMed

PubMed

TitleDatePubMed
Mechanistic study of the spiroindolones: a new class of antimalarials.
2012 Aug 24
The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector.
2012 Jul
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 Oct
Patents

Patents

Sample Use Guides

30 mg once a day for three days
Route of Administration: Oral
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.
Substance Class Chemical
Created
by admin
on Thu Jul 06 14:40:51 UTC 2023
Edited
by admin
on Thu Jul 06 14:40:51 UTC 2023
Record UNII
Z7Q4FWA04P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CIPARGAMIN
INN   WHO-DD  
INN  
Official 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
KAE-609
Code English
NITD-609, (+)-
Code English
cipargamin [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 746820
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
FDA ORPHAN DRUG 595417
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
Code System Code Type Description
FDA UNII
Z7Q4FWA04P
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
PUBCHEM
44469321
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
SMS_ID
100000163596
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
EPA CompTox
DTXSID70152424
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
INN
9865
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
CAS
1193314-23-6
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
DRUG BANK
DB12306
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
WIKIPEDIA
Cipargamin
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
NCI_THESAURUS
C169853
Created by admin on Thu Jul 06 14:40:51 UTC 2023 , Edited by admin on Thu Jul 06 14:40:51 UTC 2023
PRIMARY
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TARGET ORGANISM->INHIBITOR
TARGET ORGANISM->INHIBITOR
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ACTIVE MOIETY