Mepacrine 2HCl is an acridine-derived yellow dye, previously used in the therapy and prevention of malaria and later as an antiprotozoal and immunomodulatory agent. It's also an inhibitor of phospholipase A2.
Quinacrine dihydrochloride is an orally bioavailable antimalarial agent, which possess anticancer effect both in vitro and vivo. Quinacrine (5-20 μM; 24 hours) inhibits the growth of SGC-7901 cells. Quinacrine (7.5 and 15 μM; 24 hours) induces apoptosis in SGC-7901 cells, which is associated with mitochondria-dependent signal pathway and involves p53 upregulation and caspase-3 activation pathway. Quinacrine (15 μM; 24 hours) treatment significantly increased the levels of proapoptotic proteins, including cytochrome c, Bax, and p53, and decreased the levels of antiapoptotic protein Bcl-2, thus shifting the ratio of Bax/Bcl-2 in favor of apoptosis[3]. The in vivo use of quinacrine (100mg/kg three times per week for two consecutive weeks) significantly suppressed circulating blast cells at days 30/31 and increased the median survival time (MST). The in vitro drug combination analysis yielded promising synergistic interactions when combining quinacrine with cytarabine, azacitidine and geldanamycin[4]. Quinacrine 25 mg/kg was shown to protect 70% of mice (statistically significant) from a lethal challenge with mouse-adapted EBOV (Ebola virus) with once-daily intraperitoneal dosing for 8 days[5]. QA (Quinacrine) demonstrates high degree of cytotoxicity against both immortalized and primary patient-derived cell lines with sub-micromolar 50% inhibitory concentration (IC50) values ranging from 1.2 µM (H2452) to 5.03 µM (H28). Further, QA also inhibited cellular migration and colony formation in MPM cells, demonstrated using scratch and clonogenic assays, respectively[6].
Quinacrine 2HCl/阿的平 细胞实验
Cell Line
Concentration
Treated Time
Description
References
4C8 mouse glioma cells
0.8 µM
10 hours
To evaluate the effect of quinacrine on autophagy and apoptosis in 4C8 glioma cells. Results showed that quinacrine induced LC3-II accumulation under both normoxic and hypoxic conditions, indicating increased autophagic vacuoles.
Neuro Oncol. 2013 Dec;15(12):1673-83
Primary rat cortical neurons
2 µM
16 to 24 hours
To investigate the dissociation effect of quinacrine on Aβ aggregates and its protective effect on synaptic function. Results showed that quinacrine treatment significantly reduced Aβ-induced neuronal cell death and synaptic dysfunction.
Sci Rep. 2021 Jun 8;11(1):12043
4C8 mouse glioma cells
2.5 µM
24 hours
To assess the effect of quinacrine on autophagic vacuole formation in 4C8 glioma cells. Fluorescence microscopy revealed punctate RFP-LC3 distribution in quinacrine-treated cells, indicating increased autophagic vacuoles.
Neuro Oncol. 2013 Dec;15(12):1673-83
Lung cancer H1299 cells
7 µM and 10 µM
24 hours
FER overexpression confers resistance to quinacrine
Proc Natl Acad Sci U S A. 2011 May 10;108(19):7968-73
Quinacrine showed competitive inhibition against SARS-CoV-2 3CLpro with an IC50 value of 7.8±0.6 µM.
Viruses. 2021 May 10;13(5):873
GBM-I neurospheres
5.43 µM (IC50)
48 hours
Evaluate the inhibitory effect of SI113 combined with Quinacrine on the growth of GBM-I neurospheres, showing a synergistic effect.
J Exp Clin Cancer Res. 2019 May 17;38(1):202
GBM3-Luc neurospheres
4.79 µM (IC50)
48 hours
Evaluate the inhibitory effect of SI113 combined with Quinacrine on the growth of GBM3-Luc neurospheres, showing a synergistic effect.
J Exp Clin Cancer Res. 2019 May 17;38(1):202
T98G glioblastoma cells
2.18 µM (IC50)
48 hours
Evaluate the inhibitory effect of SI113 combined with Quinacrine on the growth of T98G cells, showing a synergistic effect.
J Exp Clin Cancer Res. 2019 May 17;38(1):202
U373MG glioblastoma cells
2.39 µM (IC50)
48 hours
Evaluate the inhibitory effect of SI113 combined with Quinacrine on the growth of U373MG cells, showing a synergistic effect.
J Exp Clin Cancer Res. 2019 May 17;38(1):202
ADF human glioblastoma cells
2.46 µM (IC50)
48 hours
Evaluate the inhibitory effect of SI113 combined with Quinacrine on the growth of ADF cells, showing a synergistic effect.
J Exp Clin Cancer Res. 2019 May 17;38(1):202
Human colon cancer RKO cells
10 µM
48 hours
To screen for quinacrine-resistant cell lines and found that overexpression of FER tyrosine kinase confers resistance
Proc Natl Acad Sci U S A. 2011 May 10;108(19):7968-73
Vero E6 cells
0-30 µM
48 hours
Evaluate the inhibitory effect of Quinacrine on SARS-CoV-2 viral replication, results showed that Quinacrine significantly reduces viral replication and virus cytotoxicity.
Viruses. 2021 Jan 17;13(1):121
RKM+ cells
1 µM
6 days
To assess the effect of quinacrine on mouse PrPSc accumulation, results showed more than threefold reduction in PrPSc levels
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6028-33
SMB cells
1 µM
6 days
To assess the effect of quinacrine on mouse PrPSc accumulation, results showed 5- to 14-fold reductions in PrPSc levels
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6028-33
ScN2a cells
1 µM
6 days
To assess the effect of quinacrine on mouse PrPSc accumulation, results showed 5- to 14-fold reductions in PrPSc levels
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6028-33
Elk21+ cells
1 µM
6 days
To assess the effect of quinacrine on CWD PrPSc accumulation, results showed more than twofold increase in PrPSc levels
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6028-33
Elk21+ cells
1 µM
60 days
To assess the long-term effect of quinacrine on CWD PrPSc accumulation, results showed approximately sevenfold increase in PrPSc levels
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6028-33
4C8 mouse glioma cells
2 µM
72 hours
To evaluate the effect of quinacrine on apoptosis in 4C8 glioma cells. Results showed that combined quinacrine and cediranib treatment under hypoxic conditions significantly increased cleaved caspase-3 expression.
Neuro Oncol. 2013 Dec;15(12):1673-83
RKD+ cells
1 µM
8 passages
To assess the effect of quinacrine on deer PrPSc accumulation, results showed more than twofold increase in PrPSc levels
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6028-33
Quinacrine 2HCl/阿的平 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Male Sprague Dawley rats
Cisplatin-induced nephrotoxicity model
Intraperitoneal injection
10 mg/kg/day
Once daily for 10 days
Quinacrine ameliorates cisplatin-induced renal toxicity via upregulating SIRT-1, downregulating inflammatory markers (ICAM-1 and TNF-α), reducing oxidative stress, and inhibiting apoptosis.
Int J Mol Sci. 2021 Oct 1;22(19):10660
5XFAD transgenic mice
Alzheimer’s disease model
Intravenous injection
2 mg/kg
Once a week for 6 weeks
To evaluate the dissociation effect of quinacrine on Aβ plaques and its impact on AD-related protein expression. Results showed that quinacrine significantly reduced the number and size of Aβ plaques and decreased astrocytosis.
Sci Rep. 2021 Jun 8;11(1):12043
Human
Patients with sporadic CJD
Oral
200-600 mg/day
Once daily for 2-8 weeks
To evaluate the safety and efficacy of quinacrine combined with a P-glycoprotein inhibitor in treating Creutzfeldt-Jakob disease. Results showed that low-dose quinacrine combined with verapamil improved clinical symptoms without liver dysfunction or hematological toxicity.
Cell Mol Neurobiol. 2004 Dec;24(6):873-5
Transgenic mice
CWD infection model
Oral
30 mg/kg/day
Daily administration until terminal disease signs
To assess the effect of quinacrine on CWD disease progression, results showed no significant effect on disease onset time or PrPSc accumulation
Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):6028-33
CD1 mice
RML prion infection model
Oral
40 mg/kg/day
Once daily for 43-60 days
Combination of quinacrine with γ-secretase inhibitor reduced PrPSc by ≈95% in the neocortex and hippocampus and ≈50% in the thalamus, and prevented dendritic atrophy and loss.
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10595-600
C57BL/6×DBA/2F1 hybrid mice
Intracranial 4C8 mouse glioma model
Oral gavage
50 mg/kg
Daily until the end of the experiment
To evaluate the antivascular and antitumor efficacy of quinacrine in intracranial glioma. Results showed that quinacrine alone had no significant effect on tumor growth or survival, but combined with cediranib significantly reduced tumor growth (>2-fold) and increased median survival (>2-fold).
Withdrawn(reevaluation of comp... 展开 >>ound development) 收起 <<
January 2008
United States, New York
... 展开 >>
Community Care Physicians
Albany, New York, United States, 12208
United States, North Carolina
ClinWorks Cancer Research Center
Charlotte, North Carolina, United States, 28207 收起 <<
Withdrawn(reevaluation of comp... 展开 >>ound development) 收起 <<
January 2008
United States, New York
... 展开 >>
Community Care Physicians
Albany, New York, United States, 12208
United States, North Carolina
ClinWorks Cancer Research Center
Charlotte, North Carolina, United States, 28207 收起 <<
United States, Pennsylvania
... 展开 >>
Fox Chase Cancer Center
Recruiting
Philadelphia, Pennsylvania, United States, 19011
Contact: Wafik El-Deiry 215-214-4233
Principal Investigator: Wafik S. El-Deiry, MD 收起 <<
Recurrent Non-small Cell Lung ... 展开 >>Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer 收起 <<
Phase 1
Completed
-
United States, Ohio
... 展开 >>
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer
Cleveland, Ohio, United States, 44106 收起 <<
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