U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H33N3O
Molecular Weight 343.5062
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SITAMAQUINE

SMILES

CCN(CC)CCCCCCNC1=CC(OC)=CC2=C1N=CC=C2C

InChI

InChIKey=RVAKDGYPIVSYEU-UHFFFAOYSA-N
InChI=1S/C21H33N3O/c1-5-24(6-2)14-10-8-7-9-12-22-20-16-18(25-4)15-19-17(3)11-13-23-21(19)20/h11,13,15-16,22H,5-10,12,14H2,1-4H3

HIDE SMILES / InChI

Molecular Formula C21H33N3O
Molecular Weight 343.5062
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16945323

Sitamaquine (WR-6026) is an orally active 8-aminoquinoline analog in development by the Walter Reed Army Institute, in collaboration with GlaxoSmithKline (formerly SmithKline Beecham), for the potential treatment of visceral leishmaniasis. Phase III trials for the treatment of visceral leishmaniasis had been initiated by March 2002, at which time GlaxoSmithKline hoped to file an MAA in 2003. By 1999, the compound had also undergone phase I trials in HIV-infected individuals for the treatment of Pneumocystis carinii infection. Preclinical studies have been conducted in primates and rodents for the potential treatment of Babesia microti infection.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
29.2 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
484.3 ng/mL
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
577 ng/mL
2 mg/kg single, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
451 ng/mL
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
503 ng/mL
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
639 ng/mL
2 mg/kg 1 times / day single, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6916 ng × h/mL
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7147 ng × h/mL
2 mg/kg single, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7723 ng × h/mL
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
8350 ng × h/mL
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8574 ng × h/mL
2 mg/kg 1 times / day single, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
19.3 h
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
18.3 h
2 mg/kg 1 times / day multiple, oral
dose: 2 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SITAMAQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
DLT: Elevated triglycerides...
Disc. AE: Skin rash, Nausea...
Dose limiting toxicities:
Elevated triglycerides (5.6%)
AEs leading to
discontinuation/dose reduction:
Skin rash (11.1%)
Nausea (5.6%)
Vomiting (5.6%)
Headache (5.6%)
CPK increased (5.6%)
LDH increased (5.6%)
AST increased (5.6%)
ALT increased (5.6%)
Sources: Page: p.29
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
DLT: Methemoglobinemia, Methemoglobinemia...
Disc. AE: Histoplasmosis, Fever...
Dose limiting toxicities:
Methemoglobinemia (12.5%)
Methemoglobinemia (37.5%)
Elevated triglycerides (12.5%)
AEs leading to
discontinuation/dose reduction:
Histoplasmosis (12.5%)
Fever (12.5%)
Flushing (12.5%)
Skin rash (12.5%)
Sources: Page: p.29
2.5 mg/kg 1 times / day multiple, oral
Studied dose
Dose: 2.5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg/kg, 1 times / day
Sources: Page: p.1008
unhealthy, CHILD,ADULT
n = 28
Health Status: unhealthy
Condition: visceral leishmaniasis
Age Group: CHILD,ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.1008
Disc. AE: Bone marrow depression, Acute renal failure...
AEs leading to
discontinuation/dose reduction:
Bone marrow depression (3.6%)
Acute renal failure (3.6%)
Bone marrow depression (3.6%)
Cardio-respiratory failure (grade 5, 3.6%)
Nephrotic syndrome (7.2%)
Glomerulonephritis (7.2%)
Sources: Page: p.1008
AEs

AEs

AESignificanceDosePopulation
Skin rash 11.1%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
Elevated triglycerides 5.6%
DLT
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
ALT increased 5.6%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
AST increased 5.6%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
CPK increased 5.6%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
Headache 5.6%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
LDH increased 5.6%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
Nausea 5.6%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
Vomiting 5.6%
Disc. AE
120 mg 1 times / day multiple, oral
MTD
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 18
Sources: Page: p.29
Elevated triglycerides 12.5%
DLT
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
Methemoglobinemia 12.5%
DLT, Disc. AE
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
Fever 12.5%
Disc. AE
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
Flushing 12.5%
Disc. AE
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
Histoplasmosis 12.5%
Disc. AE
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
Skin rash 12.5%
Disc. AE
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
Methemoglobinemia 37.5%
DLT
150 mg 1 times / day multiple, oral
Studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.29
unhealthy, ADULT
n = 8
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.29
Acute renal failure 3.6%
Disc. AE
2.5 mg/kg 1 times / day multiple, oral
Studied dose
Dose: 2.5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg/kg, 1 times / day
Sources: Page: p.1008
unhealthy, CHILD,ADULT
n = 28
Health Status: unhealthy
Condition: visceral leishmaniasis
Age Group: CHILD,ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.1008
Bone marrow depression 3.6%
Disc. AE
2.5 mg/kg 1 times / day multiple, oral
Studied dose
Dose: 2.5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg/kg, 1 times / day
Sources: Page: p.1008
unhealthy, CHILD,ADULT
n = 28
Health Status: unhealthy
Condition: visceral leishmaniasis
Age Group: CHILD,ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.1008
Bone marrow depression 3.6%
Disc. AE
2.5 mg/kg 1 times / day multiple, oral
Studied dose
Dose: 2.5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg/kg, 1 times / day
Sources: Page: p.1008
unhealthy, CHILD,ADULT
n = 28
Health Status: unhealthy
Condition: visceral leishmaniasis
Age Group: CHILD,ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.1008
Glomerulonephritis 7.2%
Disc. AE
2.5 mg/kg 1 times / day multiple, oral
Studied dose
Dose: 2.5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg/kg, 1 times / day
Sources: Page: p.1008
unhealthy, CHILD,ADULT
n = 28
Health Status: unhealthy
Condition: visceral leishmaniasis
Age Group: CHILD,ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.1008
Nephrotic syndrome 7.2%
Disc. AE
2.5 mg/kg 1 times / day multiple, oral
Studied dose
Dose: 2.5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg/kg, 1 times / day
Sources: Page: p.1008
unhealthy, CHILD,ADULT
n = 28
Health Status: unhealthy
Condition: visceral leishmaniasis
Age Group: CHILD,ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.1008
Cardio-respiratory failure grade 5, 3.6%
Disc. AE
2.5 mg/kg 1 times / day multiple, oral
Studied dose
Dose: 2.5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2.5 mg/kg, 1 times / day
Sources: Page: p.1008
unhealthy, CHILD,ADULT
n = 28
Health Status: unhealthy
Condition: visceral leishmaniasis
Age Group: CHILD,ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 28
Sources: Page: p.1008
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 23.1093 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models.
1991 Feb
New drug developments for opportunistic infections in immunosuppressed patients: Pneumocystis carinii.
1995 Nov 24
Transition metal complexes of quinolino[3,2-b]benzodiazepine and quinolino[3,2-b]benzoxazepine: synthesis, characterization, and antimicrobial studies.
2007
Patents

Sample Use Guides

oral sitamaquine, 2 mg/kg/day, once a day for 21 days
Route of Administration: Oral
Sitamaquine (1 ug/ml) almost completely inhibited P carinii growth in human lung fibroblasts over 10 days. Some inhibition was seen at 0.1 ug/ml, which was a similar level of activity to that of primaquine.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:27:57 GMT 2023
Edited
by admin
on Fri Dec 15 16:27:57 GMT 2023
Record UNII
5AIJ4TGC6B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SITAMAQUINE
INN   MI   WHO-DD  
INN  
Official Name English
sitamaquine [INN]
Common Name English
WR-6026
Code English
Sitamaquine [WHO-DD]
Common Name English
SITAMAQUINE [MI]
Common Name English
Code System Code Type Description
PUBCHEM
42548
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
INN
7834
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
DRUG BANK
DB04909
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
MERCK INDEX
m9961
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY Merck Index
SMS_ID
100000129177
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
EPA CompTox
DTXSID70206395
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
FDA UNII
5AIJ4TGC6B
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
EVMPD
SUB37607
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
CAS
57695-04-2
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
NCI_THESAURUS
C73010
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
ChEMBL
CHEMBL57004
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
MESH
C080436
Created by admin on Fri Dec 15 16:27:58 GMT 2023 , Edited by admin on Fri Dec 15 16:27:58 GMT 2023
PRIMARY
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