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AM-9022 is an orally active, potent, selective KIF18A inhibitor that can be used for research on cancer[1]. | [in vivo]
AM-9022 (30-100 mg/kg; p.o.; daily for 18 or 21 days) has significant anti-cancer effects in breast and ovarian tumor models at well-tolerated doses[1].
| Animal Model: | Female athymic nude mice were injected with OVCAR-3 cells (5 x 106) subcutaneously in the right flank. Femal CB.17 SCID mice were injected with JIMT-1 cells (1.0?×?107) subcutaneously in the right flank) (6-8 weeks)[1] | | Dosage: | 30 mg/kg (OVCAR-3 CDX tumors mice); 30, 100 mg/kg (JIMT-1 tumors mice) | | Administration: | Oral gavage (p.o.); daily for 18 days or 21 days | | Result: | Increased pH3 mitotic marker levels in OVCAR-3 tumors by 3.4-fold, with higher compound exposure in tumors relative to plasma in OVCAR-3 CDX tumors mice.
Inhibited tumor growth, with evidence of tumor regression (TR) (95% TR, six of ten tumor-free mice) and no body weight loss in OVCAR-3 CDX tumors mice.
Inhibited tumor growth with evidence of TR (16% and 94% TR, respectively) at well-tolerated doses in JIMT-1 tumors mice.
The plasma AUC value at 30?mg/kg was 3.7-fold higher in the JIMT-1 model relative to the OVCAR-3 model.
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| [References]
[1] Payton M, et al. Small-molecule inhibition of kinesin KIF18A reveals a mitotic vulnerability enriched in chromosomally unstable cancers. Nat Cancer. 2023 Dec 27. DOI:10.1038/s43018-023-00699-5 |
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