Delving into the Latest Updates on Mepacrine hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-methoxy-6-chloro-9-diethylaminopentylaminoacridine, 3-chloro-7-methoxy-9-(1-methyl-4-diethylaminobutylamino)acridine, 6-chloro-9-((4-(diethylamino)-1-methylbutyl)amino)-2-methoxyacridine

+ [15]

Target

NF-κB x p53 x sPLA2

Mechanism

NF-κB inhibitors(Nuclear factor NF-kappa-B complex inhibitors), p53 modulators(Tumor protein p53 modulators), sPLA2 inhibitors(Secretory phospholipase A2 inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesDigestive System Disorders+ [2]

Active Indication

GiardiasisLeishmaniasisMalaria+ [1]

Inactive Indication

Advanced Renal Cell CarcinomaCastration-Resistant Prostatic CancerCreutzfeldt-Jakob Disease, Sporadic+ [5]

Originator Organization

Bayer AG

Active Organization

Bayer AG

The Third Affiliated Hospital, Sun Yat-Sen University

Inactive Organization

Cleveland BioLabs, Inc.

Incuron LLC

National Cancer Institute

+ [1]

Drug Highest PhaseApproved

First Approval Date

(01 Jan 1932),

GiardiasisLeishmaniasisMalaria+ [1]

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC23H36Cl3N3O3

InChIKeyRZFNKJVCPDLQQA-UHFFFAOYSA-N

CAS Registry6151-30-0

View All Structures (2)

AIMSThis study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling.MATERIALS AND METHODSFive groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days.KEY FINDINGSResults showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP.SIGNIFICANCEThese findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.

26 Nov 2024·The American Journal of Tropical Medicine and Hygiene

Splenic Modulation of Plasmodium vivax Relapses and Hypnozoite Activation during the Second World War?

Article

Author: Shanks, G. Dennis

Despite their colonial experience with tropical medicine, Allied (United States, United Kingdom, Australia, and India) Armies in the Indo-Pacific region were surprised by the large number of Plasmodium vivax infections in their soldiers during the Second World War. Even after the institution of effective chemoprophylaxis with quinacrine, multiple cycles of clinical relapses often occurred when months of medication was discontinued. Nearly monthly symptomatic relapses (>10) were not unusual and resulted in important manpower losses after each campaign. Retrospective consideration suggests that small splenic size was associated with the risk of recurrent clinical episodes of vivax malaria. Potential non–mutually exclusive explanations for frequent relapses of vivax malaria in soldiers are reviewed. These include decreased retention of parasitized red blood cells by small spleens through greater filtration stringency preventing relapses from becoming clinically patent; small spleen size being a marker of lower innate and/or acquired immunity, modulating the risk of clinically patent recurrences; or small spleen size increasing the number of relapses through decreased removal of triggers of hypnozoite activation. Apparent splenic modulation of vivax malaria relapses suggests a complex interaction between the parasite and host that might be amenable to manipulation to facilitate malaria elimination.

12 Oct 2024·Expert Opinion on Pharmacotherapy

Elucidating the mechanisms and efficacy of antimalarial drugs in systemic lupus erythematosus

Review

Author: Paredes-Ruiz, Diana ; Ruiz-Irastorza, Guillermo ; Amo, Laura ; Martin-Iglesias, Daniel

INTRODUCTIONAntimalarials (AMs) are old drugs with a wide range of beneficial effects in systemic lupus erythematosus (SLE) beyond the control of activity. The most recent debate is focused on defining the optimal doses to assure the best benefit/risk ratio.AREAS COVEREDWe have reviewed the pharmacological basis underlying the various therapeutic effects of AMs and the beneficial and toxic effects of HCQ, also discussing the role of mepacrine not only as a substitute in cases of maculopathy, but also as a very effective therapy combined with HCQ. We searched PubMed and Embase for articles published in English at any time. We used the terms "hydroxychloroquine" or "mepacrine" or "chloroquine" or "antimalarials", "pharmacokinetics", "efficacy", "remission", "toxicity", "adherence". We reviewed original research articles, large observational studies, systematic reviews, and expert consensus statements. Additionally, studies were identified through the assessment of the reference lists of the evaluated manuscripts.EXPERT OPINIONWe advocate for the widespread use of HCQ at stable doses of 200 mg/d (≤4 mg/kg/d for most patients) and also for the early combination therapy with mepacrine to assure a good control of SLE activity, and also a durable and safe use of these essential drugs for the management of SLE.

100 Deals associated with Mepacrine hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Mepacrine hydrochloride	P01AX05	DB01103

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Giardiasis	-	Bayer AG	01 Jan 1932
Leishmaniasis	-	Bayer AG	01 Jan 1932
Malaria	-	Bayer AG	01 Jan 1932
Systemic Lupus Erythematosus	-	Bayer AG	01 Jan 1932

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Renal Cell Carcinoma	Phase 2	US	Cleveland BioLabs, Inc.	01 Nov 2007
Systemic Lupus Erythematosus	Preclinical	CN	The Third Affiliated Hospital, Sun Yat-Sen University	25 Oct 2013
Castration-Resistant Prostatic Cancer	Preclinical	-	Cleveland BioLabs, Inc.	01 Dec 2006
Metastatic Prostate Carcinoma	Preclinical	-	Cleveland BioLabs, Inc.	01 Dec 2006
Prostatic Cancer	Preclinical	US	Incuron LLC	16 Nov 2006
Creutzfeldt-Jakob Disease, Sporadic	Preclinical	US	National Institute on Aging	01 Apr 2005
Liver Cancer	Preclinical	RU	Incuron LLC	-
Malignant ascites	Preclinical	RU	Incuron LLC	-
Non-Small Cell Lung Cancer	Preclinical	US	National Cancer Institute	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01844076 (CTgov)	Phase 1/2	Adenocarcinoma of large intestine \| Advanced Colorectal Adenocarcinoma	19	Quinacrine+Capecitabine (Phase I Level -2)	fefutcwesx(vflvrkzias) = zxpzczwlrs yglxtlqfkh (edfeogmvul, ybgfkngpvz - ixjcwimmke) View more	-	25 Mar 2021
				Quinacrine+Capecitabine (Phase I Level -1)	fefutcwesx(vflvrkzias) = bzfudktyvs yglxtlqfkh (edfeogmvul, gybfjowcxm - ggractfzsj) View more
NCT01844076 (ASCO2019)	Phase 1	Metastatic colon cancer	10	Quinacrine plus Capecitabine	(jbggnkrsdc) = ugpgbtoxcq tnuhgmgoqu (wwxyebhthx ) View more	-	26 May 2019
NCT00183092 (CTgov)	Phase 2	Creutzfeldt-Jakob Disease, Sporadic	69	Placebo (Placebo)	qvrnycpcni(xujzuwaecm) = wjiflozgug znprxleapl (aeyylklkkl, hptkxmhawj - yhiilaibjm) View more	-	29 May 2014
				Quinacrine (Quinacrine)	qvrnycpcni(xujzuwaecm) = wtqtjwvjic znprxleapl (aeyylklkkl, numsgkfrul - igeaxjojnm) View more
AACR2013	Not Applicable	Glioma	-	Cediranib	rnnkkumkan(boaerdeddn) = Quin may also stimulate autophagic flux, consistent with its reported inhibition of PI3K/Akt/mTOR signaling bmjamffeph (uvwewhyoao ) View more	-	15 Apr 2013
				Quinacrine
NCT00417274 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer \| Metastatic Prostate Carcinoma	31	Quinacrine	kfwhnxausl(qtpaylmdln) = hvfdlqfvyc tvbhqeyimi (riuxdkaeoa, jvqzjokwbp - aacznhkkiz) View more	-	11 Apr 2013