A8628-1ml | Chloroquine diphosphate [50-63-5] Clinisciences

Background

Chloroquine diphosphate is used as an antimalarial drug and also functions to increase sensitivity of tumor cells to radiation and chemotherapy via inducing autophagy [1].

Chloroquine diphosphate has been reported as an adjuvant for radiation and chemotherapy for inducing cell autophagy to anti-cancer cells proliferation or metastasis [2]. The mechanism of chloroquine diphosphate inducing cells autophagy is arresting cells in G1, up-regulates the expression of p27 and p53 while down-regulates the expression of CDK2 and cyclin D1 [3].

Apart from anti-malarial, chloroquine diphosphate also has long been reported functioning in cell apoptosis. Pretreated CNE-2 human nasopharyngeal carcinoma cells with chloroquine diphosphate enhanced ionizing radiation induced cell apoptosis via increasing cells autophagic ratio [4]. When treated with mouse breast cancer 4T1 cells, chloroquine diphosphate treatment inhibited cellular proliferation and viability which resulted in cells apoptosis in a time- and dose- dependent manner [2]. In human colon cancer DLD-1 cells, combination of 5-FU and chloroquine diphosphate could inhibit cells proliferation via inducing autophagy [3].

In mouse model with 4T1 cells subcutaneous xenograft, chloroquine diphosphate treatment significantly inhibited tumor growth and tumor cells metastasis to the lung, thus enhanced the mice survival [2]. In BALB/c mice injected with colon26 cells subcutaneously, chloroquine diphosphate cooperated with 5-FU significantly enhanced the inhibition of tumor growth induced by 5-FU through increasing the ratio of apoptotic cells [5].

References:
[1]. Gewirtz, D.A., An autophagic switch in the response of tumor cells to radiation and chemotherapy. Biochem Pharmacol, 2014. 90(3): p. 208-11.
[2]. Jiang, P.D., et al., Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother, 2010. 64(9): p. 609-14.
[3]. Choi, J.H., et al., Chloroquine enhances the chemotherapeutic activity of 5-fluorouracil in a colon cancer cell line via cell cycle alteration. APMIS, 2012. 120(7): p. 597-604.
[4]. Zhou, Z.R., et al., Poly(ADP-ribose) polymerase-1 regulates the mechanism of irradiation-induced CNE-2 human nasopharyngeal carcinoma cell autophagy and inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells. Oncol Rep, 2013. 29(6): p. 2498-506.
[5]. Sasaki, K., et al., Resistance of colon cancer to 5-fluorouracil may be overcome by combination with chloroquine, an in vivo study. Anticancer Drugs, 2012. 23(7): p. 675-82.

Product Citation

1. Ting Yao, Yu Huang, et al. "Response mechanisms to acid stress promote LF82 replication in macrophages." Front Cell Infect Microbiol. 2023 Oct 10:13:1255083. PMID: 37881369
2. Yang Du, Yaqiong Shang, et al. "Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis." Cell Death Dis. 2023 Aug 29;14(8):571. PMID: 37640723
3. Mingchao Mu, Qin Zhang, et al. "3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis." Cancer Gene Ther. 2023 Aug 9. PMID: 37558749
4. Yuhui Yang, Hao Liu, et al. "Autophagy mediates cementoblast mineralization under compression through periostin/β‐catenin axis." J Cell Physiol. 2023 Jul 21. PMID: 37475648
5. Zhenhua Feng, Siyue Tao, et al. "The deubiquitinase UCHL1 negatively controls osteoclastogenesis by regulating TAZ/NFATC1 signalling." Int J Biol Sci. 2023 Apr 24;19(8):2319-2332. PMID: 37215988
6. Weiran Li, Yuhui Yang, et al. "Autophagy mediates cementoblast mineralization through periostin/β-catenin signaling axis under compression." Research Square October 13th, 2022.
7. Zhaodi Wang, Yukang Wen, et al. "Incomplete autophagy promotes the replication of Mycoplasma hyopneumoniae." J Microbiol. 2021 Aug;59(8):782-791. PMID: 34219210
8. Yuhui Yang, Yiping Huang, et al. "Compressive force regulates cementoblast migration via downregulation of autophagy." J Periodontol. 2021 Nov;92(11):128-138. PMID: 34231875
9. Jun Wang, Wei Tang, et al. "Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy." Biomaterials. 2021 Jun;273:120784. PMID: 33848731
10. JIN WANG, DONG LIANG, et al. "Novel PI3K/Akt/mTOR signaling inhibitor, W922, prevents colorectal cancer growth via the regulation of autophagy." Int J Oncol. 2020 Nov 23;58(1):70-82. PMID: 33367926
11. Du Y, Qian Y, et al. "Chloroquine attenuates lithium-induced NDI and proliferation of renal collecting duct cells." Am J Physiol Renal Physiol. 2020;318(5):F1199-F1209. PMID: 32249612
12. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID: 31063758
13. Shan M, Qin J, et al. "Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway." Free Radic Biol Med. 2017 Jun 21. pii: S0891-5849(17)30594-4. PMID: 28647611

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Chemical Properties

Physical Appearance	A solid
Storage	Desiccate at RT
M.Wt	515.86
Cas No.	50-63-5
Formula	C₁₈H₂₆ClN₃·2H₃PO₄
Solubility	insoluble in DMSO; insoluble in EtOH; ≥106.06 mg/mL in H2O
Chemical Name	4-N-(7-chloroquinolin-4-yl)-1-N,1-N-diethylpentane-1,4-diamine;phosphoric acid
SDF	Download SDF
Canonical SMILES	CCN(CC)CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl.OP(=O)(O)O.OP(=O)(O)O
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment [1]:
Cell lines	Mouse breast cancer 4T1 cells
Preparation method	The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20°C for several months.
Reacting condition	3.125, 6.25, 12.5, 25, 50 and 100 μM; 24, 48 and 72 hrs
Applications	According to the results of the MTT assay, Chloroquine Diphosphate dose- and time-dependently inhibited proliferation of 4T1 cells.
Animal experiment [1]:
Animal models	4T1 tumor-bearing BALB/c mice
Dosage form	25 and 50 mg/kg; i.p.; q.d., for 28 days
Applications	Chloroquine Diphosphate treatment at the doses of 25 and 50 mg/kg significantly reduced the rates of primary tumor growth. In addition, 30% and 60% of mice in the 25 and 50 mg/kg Chloroquine Diphosphate-treated groups still survived on 61st day.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Jiang, P.D., et al., Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother, 2010. 64(9): p. 609-14.