Amodiaquine free base | CAS#86-42-0 | N-methyltransferase inhibitor

MedKoo Cat#: 317185 | Name: Amodiaquine free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Amodiaquine (trade names Camoquin, Flavoquine), a 4-aminoquinoline compound related to chloroquine, is used as an antimalarial and anti-inflammatory agent. Amodiaquine has been shown to be more effective than chloroquine in treating chloroquine-resistant Plasmodium falciparum malaria infections and may give more protection than chloroquine when used as weekly prophylaxis. Amodiaquine, like chloroquine, is generally well tolerated. Amodiaquine is a histamine N-methyltransferase inhibitor. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Chemical Structure

Amodiaquine free base

CAS#86-42-0 (free base)

Theoretical Analysis

MedKoo Cat#: 317185

Name: Amodiaquine free base

CAS#: 86-42-0 (free base)

Chemical Formula: C20H22ClN3O

Exact Mass: 355.1451

Molecular Weight: 355.86

Elemental Analysis: C, 67.50; H, 6.23; Cl, 9.96; N, 11.81; O, 4.50

Price and Availability

Size	Price	Availability
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 850.00	Ready to ship
1g	USD 1,450.00	Ready to ship
2g	USD 2,450.00	Ready to ship
5g	USD 4,250.00	Ready to ship

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Related CAS #

86-42-0 (free base) 69-44-3 (HCl) 6398-98-7 (HCl hydrate)

Synonym

Camochin; Camoquin; Camoquinal; Camoquine; Flavoquine; Miaquin; NSC 13453; SN-10751; Amodiaquine free base

IUPAC/Chemical Name

4-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol

InChi Key

OVCDSSHSILBFBN-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H22ClN3O/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)

SMILES Code

CCN(CC)CC1=C(C=CC(=C1)NC2=C3C=CC(=CC3=NC=C2)Cl)O

Appearance

Solid powder

Purity

>95% (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, not in water

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A20T10K23

QC Data

View QC data: current batch, Lot#A20T10K23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Amodiaquine (Amodiaquin), a 4-aminoquinoline class of antimalarial agent, is a potent histamine N-methyltransferase inhibitor and Nurr1 agonist that specifically binds to Nurr1-LBD (ligand binding domain) with an EC50 of ~20 μM.

In vitro activity:

Cells treated with 1–10 μM AQ (Amodiaquine) for 6 h accumulated lysosomes (LAMP1-positive puncta) (Fig. 3a, b) while concentrations between 10 and 20 μM further enhanced autophagosome accumulation (Fig. 3c, d; LC3B puncta). Notably, 10–20 μM AQ also induced generation of nucleolar caps (Fig. 3c), showing that both autophagy inhibition and nucleolar stress take place simultaneously. Strikingly, even though AQ and CQ showed similar levels of lipidated LC3 (LC3-II) (Fig. 2a) and accumulation of cytoplasmic vesicles (Fig. 3e), only AQ caused remarkable condensation of nucleolar chromatin (Fig. 3e). Among the 4aminoquinoline family members, CQ and H-CQ inhibit autophagy with efficiency similar to AQ, but RPA194 degradation and p53 stabilization was only induced by AQ (Fig. 3f). Furthermore, only AQ induced a strong reduction of 47S rRNA synthesis among all autophagy inhibitors tested (Fig. 3g). Overall, these findings indicate that ribosome biogenesis stress is not a general consequence of autophagy inhibition and that AQ stands out among the 4-aminoquinoline family as a compound operating through two independent mechanisms: autophagy inhibition in the cytoplasm and ribosome biogenesis stress in the nucleolus. Taken together, the data reveals unsuspected activity of a drug approved and used in the clinics for over 30 years, and provide rationale for repurposing amodiaquine in cancer therapy. Reference: Cell Death Differ. 2020 Feb; 27(2): 773–789. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205879/

In vivo activity:

To confirm the immune suppression by AQ in vivo, mice were fed DSS and intraperitoneally injected with either vehicle or AQ. Body weight loss and colon shortening were induced in the DSS-treated group, but these changes were attenuated in the AQ-treated group (Fig. 7A,B). Histological examination demonstrated that AQ reduced the immune cell infiltration and inhibited epithelial cell destruction with goblet cell depletion in the DSS-induced colitis model (Fig. 7C). Furthermore, T cell-induced colitis in recombinaseactivating gene (RAG) knockout (KO) mice was diminished by administration with AQ, as demonstrated by the decreases in disease activity index and histopathology (Fig. 7D,E). Foxp3+ Treg cells were more frequently found in AQ-treated colon tissues (Fig. 7E). Consistently, AQ administration increased the expression of Foxp3, but decreased the expression of inflammatory markers RORγt and T-bet (Fig. 7F). Moreover, the inflammatory cytokines IL-17 and IFN-γ produced by inflammatory T cells were significantly diminished in the AQ-treated group (Fig. 7G). The ability of anti-malarial AQ to potentiate iTreg cell development makes it a promising drug for preventing and treating inflammatory and autoimmune diseases. Reference: Sci Rep. 2017 Dec 5;7(1):16946. https://pubmed.ncbi.nlm.nih.gov/29208963/

	Solvent	mg/mL	mM
Solubility
	DMSO	38.0	106.78
	Ethanol	12.0	33.72

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 355.86 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. Won HY, Shin JH, Oh S, Jeong H, Hwang ES. Enhanced CD25+Foxp3+ regulatory T cell development by amodiaquine through activation of nuclear receptor 4A. Sci Rep. 2017 Dec 5;7(1):16946. doi: 10.1038/s41598-017-17073-y. PMID: 29208963; PMCID: PMC5717225. 2. Espinoza JA, Zisi A, Kanellis DC, Carreras-Puigvert J, Henriksson M, Hühn D, Watanabe K, Helleday T, Lindström MS, Bartek J. The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity. Cell Death Differ. 2020 Feb;27(2):773-789. doi: 10.1038/s41418-019-0387-5. Epub 2019 Jul 8. PMID: 31285544; PMCID: PMC7205879. 3. DeWald LE, Johnson JC, Gerhardt DM, Torzewski LM, Postnikova E, Honko AN, Janosko K, Huzella L, Dowling WE, Eakin AE, Osborn BL, Gahagen J, Tang L, Green CE, Mirsalis JC, Holbrook MR, Jahrling PB, Dyall J, Hensley LE. In Vivo Activity of Amodiaquine against Ebola Virus Infection. Sci Rep. 2019 Dec 27;9(1):20199. doi: 10.1038/s41598-019-56481-0. PMID: 31882748; PMCID: PMC6934550.

In vitro protocol:

In vivo protocol:

1: Gil JP. Amodiaquine pharmacogenetics. Pharmacogenomics. 2008 Oct;9(10):1385-90. doi: 10.2217/14622416.9.10.1385. PMID: 18855526. 2: Olliaro P, Mussano P. Amodiaquine for treating malaria. Cochrane Database Syst Rev. 2000;(2):CD000016. doi: 10.1002/14651858.CD000016. Update in: Cochrane Database Syst Rev. 2003;(2):CD000016. PMID: 10796468. 3: Olliaro P, Mussano P. Amodiaquine for treating malaria. Cochrane Database Syst Rev. 2003;(2):CD000016. doi: 10.1002/14651858.CD000016. PMID: 12804382. 4: Bloland PB, Ruebush TK. Amodiaquine. Lancet. 1996 Dec 14;348(9042):1659-60. doi: 10.1016/S0140-6736(05)65723-6. PMID: 8962005. 5: Sirima SB, Gansané A. Artesunate-amodiaquine for the treatment of uncomplicated malaria. Expert Opin Investig Drugs. 2007 Jul;16(7):1079-85. doi: 10.1517/13543784.16.7.1079. PMID: 17594191. 6: Gillespie P, Wagner F. Amodiaquine agranulocytosis. Med J Aust. 1977 Feb 26;1(9):298-9. doi: 10.5694/j.1326-5377.1977.tb130706.x. PMID: 859490. 7: Olliaro P, Nevill C, LeBras J, Ringwald P, Mussano P, Garner P, Brasseur P. Systematic review of amodiaquine treatment in uncomplicated malaria. Lancet. 1996 Nov 2;348(9036):1196-201. doi: 10.1016/S0140-6736(96)06217-4. PMID: 8898036. 8: Bhattarai A, Maini-Thapar M, Ali AS, Björkman A. Amodiaquine during pregnancy. Lancet Infect Dis. 2004 Dec;4(12):721-2; discussion 722. doi: 10.1016/S1473-3099(04)01198-3. PMID: 15567117. 9: McIntosh HM. Chloroquine or amodiaquine combined with sulfadoxine- pyrimethamine for treating uncomplicated malaria. Cochrane Database Syst Rev. 2001;(4):CD000386. doi: 10.1002/14651858.CD000386. Update in: Cochrane Database Syst Rev. 2005;(4):CD000386. PMID: 11687077. 10: McIntosh HM. Chloroquine or amodiaquine combined with sulfadoxine- pyrimethamine for treating uncomplicated malaria. Cochrane Database Syst Rev. 2000;(2):CD000386. doi: 10.1002/14651858.CD000386. Update in: Cochrane Database Syst Rev. 2001;(4):CD000386. PMID: 10796538. 11: Tagbor HK, Chandramohan D, Greenwood B. The safety of amodiaquine use in pregnant women. Expert Opin Drug Saf. 2007 Nov;6(6):631-5. doi: 10.1517/14740338.6.6.631. PMID: 17967151. 12: Akindele MO, Odejide AO. Amodiaquine-induced involuntary movements. Br Med J. 1976 Jul 24;2(6029):214-5. doi: 10.1136/bmj.2.6029.214. PMID: 974497; PMCID: PMC1687352. 13: Sakurai Y, Sakakibara N, Toyama M, Baba M, Davey RA. Novel amodiaquine derivatives potently inhibit Ebola virus infection. Antiviral Res. 2018 Dec;160:175-182. doi: 10.1016/j.antiviral.2018.10.025. Epub 2018 Nov 3. PMID: 30395872; PMCID: PMC6374029. 14: Willems S, Müller M, Ohrndorf J, Heering J, Proschak E, Merk D. Scaffold Hopping from Amodiaquine to Novel Nurr1 Agonist Chemotypes via Microscale Analogue Libraries. ChemMedChem. 2022 Apr 20;17(8):e202200026. doi: 10.1002/cmdc.202200026. Epub 2022 Feb 21. PMID: 35132775; PMCID: PMC9305750. 15: Hirschel B. Amodiaquine and hepatitis. Ann Intern Med. 1986 Sep;105(3):467. doi: 10.7326/0003-4819-105-3-467_1. PMID: 3740693. 16: Brasseur P. Tolérance de l'amodiaquine [Tolerance of amodiaquine]. Med Trop (Mars). 2007 Jun;67(3):288-90. French. PMID: 17784684. 17: Nair A, Abrahamsson B, Barends DM, Groot DW, Kopp S, Polli JE, Shah VP, Dressman JB. Biowaiver monographs for immediate release solid oral dosage forms: amodiaquine hydrochloride. J Pharm Sci. 2012 Dec;101(12):4390-401. doi: 10.1002/jps.23312. Epub 2012 Sep 4. PMID: 22949374. 18: DeWald LE, Johnson JC, Gerhardt DM, Torzewski LM, Postnikova E, Honko AN, Janosko K, Huzella L, Dowling WE, Eakin AE, Osborn BL, Gahagen J, Tang L, Green CE, Mirsalis JC, Holbrook MR, Jahrling PB, Dyall J, Hensley LE. In Vivo Activity of Amodiaquine against Ebola Virus Infection. Sci Rep. 2019 Dec 27;9(1):20199. doi: 10.1038/s41598-019-56481-0. PMID: 31882748; PMCID: PMC6934550. 19: Niu YR, Wei B, Chen B, Xu LH, Jing X, Peng CL, Ma TZ. Amodiaquine-induced reproductive toxicity in adult male rats. Mol Reprod Dev. 2016 Feb;83(2):174-82. doi: 10.1002/mrd.22603. Epub 2015 Dec 17. PMID: 26647924. 20: Anyorigiya TA, Castel S, Mauff K, Atuguba F, Ogutu B, Oduro A, Dosoo D, Asante KP, Owusu-Agyei S, Dodoo A, Hodgson A, Binka F, Workman LJ, Allen EN, Denti P, Wiesner L, Barnes KI. Pharmacokinetic profile of amodiaquine and its active metabolite desethylamodiaquine in Ghanaian patients with uncomplicated falciparum malaria. Malar J. 2021 Jan 6;20(1):18. doi: 10.1186/s12936-020-03553-6. Erratum in: Malar J. 2021 Mar 19;20(1):156. PMID: 33407454; PMCID: PMC7788723.