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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

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

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown
Palliative
Unknown
Palliative
Unknown
Palliative
Unknown
Palliative
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
2120 ng/mL
200 mg 3 times / day multiple, intravenous
CINCHONINE plasma
Homo sapiens
420 ng/mL
133 mg 3 times / day multiple, intravenous
CINCHONINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
13.4 μg × h/mL
20 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
22.1 μg × h/mL
15 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
23.1 μg × h/mL
30 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
29.3 μg × h/mL
25 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
35.1 μg × h/mL
35 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.8 h
133 mg 3 times / day multiple, intravenous
CINCHONINE plasma
Homo sapiens
1.41 h
20 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
2.98 h
15 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
1.65 h
30 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
2.19 h
25 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens
3.51 h
35 mg/kg 1 times / 4 weeks other, intravenous
CINCHONINE serum
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
40%
3 g 1 times / day multiple, oral
CINCHONINE plasma
Homo sapiens

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

PubMed

Sample Use Guides

In Vivo Use Guide
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.