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Sofia, R Duane; Martin, Kathryn M; Costin, James C
Anti-cancer drugs, 02/2024, Letnik: 35, Številka: 2Journal Article
This study examined the antineoplastic effects of GP-2250 (misetionamide), an oxathiazine derivative with broad activity, in multiple cancer cell lines and mouse xenograft models. Antineoplastic activity of GP-2250 was tested in >300 cancer cell lines using the OncoPanel cytotoxicity assay. GP-2250 activity was further tested in mouse xenograft models, in which GP-2250 or vehicle (10 ml/kg) was administered daily for 28 days by intraperitoneal injection in the lower right abdomen of CrTac:NCR-Foxn1nu mice with tumor volumes of 100 to 200 mm 3 . In the in-vitro models, GP-2250 increased cytotoxicity readings with IC50 and EC50 as well as indications of cell cycle blockage in pancreatic and ovarian cell lines. In mouse xenograft models, a reduction of 30-40% in tumor volume occurred in the GP-2250 group versus the vehicle group. On the final day of the study, tumor progression was significantly reduced in 4 tumor types: HT-29 in the GP-2250 500 and 1000 mg/kg groups, SKOV-3 in all GP-2250 treatment groups, Cal-27 in the GP-2250 1000 mg/kg group, and Hs-695T in the GP-2250 250 and 1000 mg/kg groups. Tumor regression in Cal-27 tumors was dose-dependent. GP-2250 demonstrated cytotoxic activity in vitro and reduced the tumor volume in a variety of human cancer cell lines in a xenograft mouse model. Given these results, as well as evidence of synergism with other anticancer drugs, GP-2250 shows promise as a new therapeutic agent for treating human cancers and is being evaluated in a phase 1 dose-escalation study (NCT03854100).
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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