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| | AM-9022 Basic information |
| Product Name: | AM-9022 | | Synonyms: | AM-9022;Benzamide, 2-(6-azaspiro[2.5]oct-6-yl)-N-[2-(4,4-difluoro-1-piperidinyl)-6-methyl-4-pyrimidinyl]-4-[[[(1R)-2-hydroxy-1-methylethyl]sulfonyl]amino]- | | CAS: | 2446872-46-2 | | MF: | C27H36F2N6O4S | | MW: | 578.68 | | EINECS: | | | Product Categories: | | | Mol File: | 2446872-46-2.mol |  |
| | AM-9022 Chemical Properties |
| density | 1.425±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted) | | pka | 7.199±0.10(predicted) | | form | Solid | | color | White to off-white |
| | AM-9022 Usage And Synthesis |
| Uses | 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 30mg/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 |
| | AM-9022 Preparation Products And Raw materials |
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