| Features: |
| Chloroquine (and its analogue hydroxychloroquine) Hydroxychloroquine (more commonly used because of its safety profile) Chloroquine originates from synthetic modifications of quinoline derivatives (it has roots in natural alkaloids like quinine) and is now produced through chemical synthesis. Its repurposing in cancer therapy centers on its ability to disrupt autophagy and lysosomal function, modulate the immune response within the tumor microenvironment, and sensitize cancer cells to chemo- and radiotherapy. Chloroquine is a synthetic derivative belonging to the 4-aminoquinoline class. It was initially developed in the 1930s from quinoline scaffolds, which themselves are derived from naturally occurring alkaloids like quinine (isolated from the bark of the cinchona tree). Unlike natural products that are directly extracted, chloroquine is produced by chemical synthesis in pharmaceutical laboratories. Pathways: -Autophagy Inhibition: By raising intralysosomal pH, chloroquine impairs the fusion of autophagosomes with lysosomes, thereby blocking autophagic flux. This inhibition can sensitize tumor cells to chemotherapy and enhance cell death. -Lysosomal Dysfunction: Chloroquine accumulates in lysosomes, altering their function. This can lead to lysosomal membrane permeabilization and subsequent activation of cell death pathways. -Stress-Related Signaling: Chloroquine-induced disruption of autophagy can lead to the accumulation of damaged proteins and organelles, triggering stress responses such as the unfolded protein response (UPR) and reactive oxygen species (ROS) generation. -TLR (Toll-Like Receptor) Signaling: There is evidence suggesting that chloroquine can inhibit TLR9 signaling Chemo- and Radiosensitization: -One of the promising uses of chloroquine in oncology is as an adjuvant to standard therapies. -By disrupting autophagy—a mechanism that many cancer cells use to survive after treatment—chloroquine can enhance the cytotoxic effects of chemotherapy and radiation. Hydroxychloroquine (more commonly used because of its safety profile) have used doses ranging from 400 mg per day up to 1200 mg per day in divided doses. Chloroquine effectiveness is pH sensitive: CQ concentrations in the whole-cell lysate were 7-fold lower at pH 6.8 as compared with pH 7.4 |
| Source: HalifaxProj(inhibit) |
| Type: |
| Also IGF1R A link between elevated IGF levels and the development of solid tumors, such as breast, colon, and prostate cancer. Gene amplification of IGF1R, which encodes insulin-like growth factor 1 receptor, is a frequent event across cancer types. Upregulation of IGF1R protein expression in tumor samples and serum in NSCLC patients. Upregulation of IGF-IR signaling can help cancer cells resist anoikis by inhibiting p53 and p21 activation. Many cancers, including breast, prostate, lung, and colorectal cancers, have been found to exhibit overexpression of IGF-1R. This overexpression can contribute to increased cell proliferation and survival, promoting tumor growth. |
| 5905- | CAR, | HCQ, | Synergistic inhibition of metastatic melanoma by carvacrol and chloroquine: an in vitro and in silico investigation of apoptosis and molecular targets |
| - | in-vitro, | Melanoma, | NA |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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