Synonym
Amodiaquin dihydrochloride; Amodiaquine hydrochloride dihydrate; Amodiaquine 2H2O HCl;
IUPAC/Chemical Name
4-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol dihydrate dihydrochloride
InChi Key
YVNAYSHNIILOJS-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H22ClN3O.2ClH.2H2O/c1-3-24(4-2)13-14-11-16(6-8-20(14)25)23-18-9-10-22-19-12-15(21)5-7-17(18)19;;;;/h5-12,25H,3-4,13H2,1-2H3,(H,22,23);2*1H;2*1H2
SMILES Code
OC1=CC=C(NC2=CC=NC3=CC(Cl)=CC=C23)C=C1CN(CC)CC.[H]O[H].[H]O[H].[H]Cl.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Amodiaquine dihydrochloride dihydrate is a histamine N-methyltransferase inhibitor.
In vitro activity:
The cytotoxicity of Amodiaquine (ADQ) and its major metabolite N-desethylamodiaquine (NADQ) and the effect of cytochrome P450 (CYP)-mediated metabolism on ADQ-induced cytotoxicity were examined. After a 48-h treatment, ADQ and NADQ caused cytotoxicity and induced apoptosis in HepG2 cells. ADQ treatment decreased the levels of anti-apoptotic Bcl-2 family proteins, which was accompanied by an increase in the levels of pro-apoptotic Bcl-2 family proteins, indicating that ADQ-induced apoptosis was mediated by the Bcl-2 family. Moreover, treatment of CYP2C8 and 3A4 overexpressing HepG2 cells with ADQ increased the phosphorylation of JNK, ERK1/2, and p38, but not the expression of Bcl-2 family proteins. These findings indicate that ADQ and its major metabolite NADQ induce apoptosis, which is mediated by members of the Bcl-2 family and the activation of MAPK signaling pathways, respectively.
Reference: Toxicol In Vitro. 2020 Feb;62:104669. https://www.sciencedirect.com/science/article/abs/pii/S0887233319304977?via%3Dihub
In vivo activity:
The anti-diabetic and anti-obesity effects of amodiaquine were evaluated in vivo. In high-fat diet-induced obese and genetically modified obese/diabetic mice, amodiaquine not only remarkably ameliorated insulin resistance, hyperlipidemia, and fatty liver but also decreased body weight gain. These findings suggest that amodiaquine exerts beneficial effects on glucose and lipid metabolism by concurrent activation of PPARα/γ. Furthermore, amodiaquine acts as an alternative insulin-sensitizing agent with a positive influence on lipid metabolism and has potential to prevent and treat type 2 diabetes while reducing the risk of lipid abnormalities.
Reference: Diabetes Obes Metab. 2018 Jul;20(7):1688-1701. https://dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.13284
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
215.14 |
| Water |
20.0 |
43.03 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
464.81
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Tang Y, Wu Q, Beland FA, Chen S, Fang JL. Apoptosis contributes to the cytotoxicity induced by amodiaquine and its major metabolite N-desethylamodiaquine in hepatic cells. Toxicol In Vitro. 2020 Feb;62:104669. doi: 10.1016/j.tiv.2019.104669. Epub 2019 Oct 16. PMID: 31629065.
2. Jung HY, Kim B, Ryu HG, Ji Y, Park S, Choi SH, Lee D, Lee IK, Kim M, Lee YJ, Song W, Lee YH, Choi HJ, Hyun CK, Holzapfel WH, Kim KT. Amodiaquine improves insulin resistance and lipid metabolism in diabetic model mice. Diabetes Obes Metab. 2018 Jul;20(7):1688-1701. doi: 10.1111/dom.13284. Epub 2018 Apr 14. PMID: 29516607.
In vitro protocol:
1. Tang Y, Wu Q, Beland FA, Chen S, Fang JL. Apoptosis contributes to the cytotoxicity induced by amodiaquine and its major metabolite N-desethylamodiaquine in hepatic cells. Toxicol In Vitro. 2020 Feb;62:104669. doi: 10.1016/j.tiv.2019.104669. Epub 2019 Oct 16. PMID: 31629065.
In vivo protocol:
1. Jung HY, Kim B, Ryu HG, Ji Y, Park S, Choi SH, Lee D, Lee IK, Kim M, Lee YJ, Song W, Lee YH, Choi HJ, Hyun CK, Holzapfel WH, Kim KT. Amodiaquine improves insulin resistance and lipid metabolism in diabetic model mice. Diabetes Obes Metab. 2018 Jul;20(7):1688-1701. doi: 10.1111/dom.13284. Epub 2018 Apr 14. PMID: 29516607.
1: Dhiman V, Singh DK, Ladumor MK, Singh S. Characterization of stress degradation products of amodiaquine dihydrochloride by liquid chromatography with high-resolution mass spectrometry and prediction of their properties by using ADMET Predictor™. J Sep Sci. 2017 Dec;40(23):4530-4540. doi: 10.1002/jssc.201700904. Epub 2017 Oct 30. PubMed PMID: 28985017.
2: Zhou T, Tan L, Cederquist GY, Fan Y, Hartley BJ, Mukherjee S, Tomishima M, Brennand KJ, Zhang Q, Schwartz RE, Evans T, Studer L, Chen S. High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain. Cell Stem Cell. 2017 Aug 3;21(2):274-283.e5. doi: 10.1016/j.stem.2017.06.017. Epub 2017 Jul 20. PubMed PMID: 28736217; PubMed Central PMCID: PMC5553280.
3: Sirikun W, Chatchawalsaisin J, Sutanthavibul N. Solid-State Characterization and Interconversion of Recrystallized Amodiaquine Dihydrochloride in Aliphatic Monohydric Alcohols. AAPS PharmSciTech. 2016 Apr;17(2):427-35. doi: 10.1208/s12249-015-0355-4. Epub 2015 Jul 24. PubMed PMID: 26206402; PubMed Central PMCID: PMC4984895.
4: Görlitzer K, Bode M, Jones PG, Jomaa H, Wiesner J. [Benzo[c][2,7]naphthyridine-5-yl-amines and benzo[h][1,6]naphthyridine-5-yl-amines--potential antimalarials]. Pharmazie. 2007 Jan;62(1):15-26. German. PubMed PMID: 17294807.
5: Looareesuwan S, Phillips RE, White NJ, Karbwang J, Benjasurat Y, Attanath P, Warrell DA. Intravenous amodiaquine and oral amodiaquine/erythromycin in the treatment of chloroquine-resistant falciparum malaria. Lancet. 1985 Oct 12;2(8459):805-8. PubMed PMID: 2864534.
6: REID ET, FRASER RJ, WILFORD FB. FIELD TRIALS WITH 3-CHLORO-9-(4-DIETHYLAMINO-1-METHYLBUTYLAMINO) ACRIDINE, 10-OXIDE DIHYDROCHLORIDE (CI-423) AS AN ANTIMALARIAL COMPOUND. Cent Afr J Med. 1963 Dec;9:478-82. PubMed PMID: 14088341.
