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

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H22N2O
Molecular Weight 294.3908
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CINCHONINE

SMILES

[H][C@@]1(C[C@@H]2CC[N@]1C[C@@H]2C=C)[C@@H](O)C3=C4C=CC=CC4=NC=C3

InChI

InChIKey=KMPWYEUPVWOPIM-QAMTZSDWSA-N
InChI=1S/C19H22N2O/c1-2-13-12-21-10-8-14(13)11-18(21)19(22)16-7-9-20-17-6-4-3-5-15(16)17/h2-7,9,13-14,18-19,22H,1,8,10-12H2/t13-,14-,18+,19-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22512909 | https://www.ncbi.nlm.nih.gov/pubmed/20768740

Cinchonine is cinchona bark alkaloid, which was used to treat malaria. Cinchonine is more efficient than quinine in increasing the intracellular accumulation and restoring the cytotoxicity of doxorubicin, mitoxantrone and vincristine on well-characterized multidrug resistance (MDR) cell lines. In the phase I of clinical trial was investigated the properties of cinchonine combined with the CHVP (cyclophosphamide, doxorubicin, vinblastine, methylprednisolone) regimen in relapsed and refractory lymphoproliferative syndromes.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2120 ng/mL
200 mg 3 times / day multiple, intravenous
dose: 200 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: QUININE
CINCHONINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
420 ng/mL
133 mg 3 times / day multiple, intravenous
dose: 133 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: QUININE
CINCHONINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13.4 μg × h/mL
20 mg/kg 1 times / 4 weeks other, intravenous
dose: 20 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
22.1 μg × h/mL
15 mg/kg 1 times / 4 weeks other, intravenous
dose: 15 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
23.1 μg × h/mL
30 mg/kg 1 times / 4 weeks other, intravenous
dose: 30 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
29.3 μg × h/mL
25 mg/kg 1 times / 4 weeks other, intravenous
dose: 25 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
35.1 μg × h/mL
35 mg/kg 1 times / 4 weeks other, intravenous
dose: 35 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.8 h
133 mg 3 times / day multiple, intravenous
dose: 133 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: QUININE
CINCHONINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1.41 h
20 mg/kg 1 times / 4 weeks other, intravenous
dose: 20 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.98 h
15 mg/kg 1 times / 4 weeks other, intravenous
dose: 15 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.65 h
30 mg/kg 1 times / 4 weeks other, intravenous
dose: 30 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.19 h
25 mg/kg 1 times / 4 weeks other, intravenous
dose: 25 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered: DOXORUBICIN
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3.51 h
35 mg/kg 1 times / 4 weeks other, intravenous
dose: 35 mg/kg
route of administration: Intravenous
experiment type: OTHER
co-administered:
CINCHONINE serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
40%
3 g 1 times / day multiple, oral
dose: 3 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CINCHONINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.
1991 Jan-Feb
Flexibility of CuCl4-tetrahedra in bis[cinchoninium tetrachlorocuprate(II)]trihydrate single crystals. X-ray diffraction and EPR studies.
2001 Aug 27
Cinchoninium L-tartrate tetrahydrate.
2001 Dec
Apoptosis induced by doxorubicin and cinchonine in P388 multidrug-resistant cells.
2001 Jul
In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T. congolense.
2001 Oct
Catalytic enantioselective fluorination of beta-keto esters by phase-transfer catalysis using chiral quaternary ammonium salts.
2002 Feb 21
Asymmetric Weitz-Scheffer epoxidation of isoflavones with hydroperoxides mediated by optically active phase-transfer catalysts.
2002 Jan 11
Unexpected change of the sense of the enantioselective hydrogenation of ethyl pyruvate catalyzed by a Pt-alumina-cinchona alkaloid system.
2002 May 21
Hydrogenation of cinchona alkaloids over supported Pt catalyst.
2003
Pharmacokinetics of idarubicin in the isolated perfused rat lung: effect of cinchonine and rutin.
2003 Jul
The relationship of physico-chemical properties and structure to the differential antiplasmodial activity of the cinchona alkaloids.
2003 Sep 1
Evidence for the 2:1 molecular recognition and inclusion behaviour between beta- and gamma-cyclodextrins and cinchonine.
2004 Aug
Synthetic cinchonidine receptors obtained by cross-linking linear poly(methacrylic acid) derivatives as an alternative molecular imprinting technique.
2004 May 5
Short columns with molecularly imprinted monolithic stationary phases for rapid separation of diastereomers and enantiomers.
2004 May 5
Bioactive cinchona alkaloids from Remijia peruviana.
2005 Mar 23
Pharmacological strategies for overcoming multidrug resistance.
2006 Jul
Time-lapse STM studies of diastereomeric cinchona alkaloids on platinum metals.
2006 Nov 2
Highly enantioselective direct aldol reaction catalyzed by cinchona derived primary amines.
2007 Sep 21
Temperature-dependent time-resolved fluorescence study of cinchonine alkaloid dication.
2008 Jan
Resolution of (+)-cinchonine and (-)-cinchonidine by phase-modulation fluorescence spectroscopy.
2009 Apr 20
Metal complexes of cinchonine as chiral building blocks: a strategy for the construction of nanotubular architectures and helical coordination polymers.
2009 Apr 22
Investigating the activity of quinine analogues versus chloroquine resistant Plasmodium falciparum.
2012 May 15
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/20769234 | https://www.ncbi.nlm.nih.gov/pubmed/3321829
relapsed and refractory lymphoproliferative syndromes: Cinchonine dihydrochloride was given as a continuous i.v. infusion from day 1 to day 3, over a 48-h period. The first dose level was 15 mg/kg/d. The following steps were defined by a 5 mg/kg/d increase of cinchonine dose over the previous step. malaria: it was injected 7(1/2) grains of cinichonine bihydrochloride into the deltoid muscle on the day before an attack was due, and warned the patient that this could not be expected to stop completely the attack due the next day
Route of Administration: Other
In Vitro Use Guide
Cinchonine at 5-10 uM induced a rapid and significant increase in the accumulation of doxorubicin, mitoxantrone, and vincristine in MDR-expressing human leukemic cell line K562/ADM.
Name Type Language
CINCHONINE
MI   WHO-DD  
Common Name English
NSC-6176
Code English
(8R,9S)-CINCHONINE
Common Name English
Cinchonine [WHO-DD]
Common Name English
CINCHONINE [MI]
Common Name English
(9S)-CINCHONAN-9-OL
Common Name English
CINCHONAN-9-OL, (9S)-
Common Name English
2-QUINUCLIDINEMETHANOL, .ALPHA.-(5-VINYL-2-QUINOLYL)-
Systematic Name English
D-CINCHONINE
Common Name English
(+)-CINCONINE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C271
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID6045082
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
CAS
118-10-5
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
MERCK INDEX
m3560
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY Merck Index
SMS_ID
100000080110
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
CHEBI
27509
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
PUBCHEM
90454
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
NSC
6176
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
ECHA (EC/EINECS)
204-234-6
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
MESH
C010086
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
NCI_THESAURUS
C75265
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
WIKIPEDIA
CINCHONINE
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
EVMPD
SUB13375MIG
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY
FDA UNII
V43X79NZCD
Created by admin on Sat Dec 16 04:54:42 UTC 2023 , Edited by admin on Sat Dec 16 04:54:42 UTC 2023
PRIMARY