| Identification | Back Directory | [Name]
Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- | [CAS]
2790567-82-5 | [Synonyms]
(S)-(4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)(3-(4-(trifluoromethyl)phenyl)morpholino)methanone
Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- | [Molecular Formula]
C22H19F3N4O3 | [MOL File]
2790567-82-5.mol | [Molecular Weight]
444.41 |
| Chemical Properties | Back Directory | [Boiling point ]
670.0±55.0 °C(Predicted) | [density ]
1.451±0.06 g/cm3(Predicted) | [form ]
Solid | [pka]
5.22±0.20(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
AMG 193 is an orally active MTA-cooperative PRMT5 inhibitor with antitumor activity. AMG 193, when complexed with MTA, preferentially inhibits the growth of MTAP-deficient tumor cells by inhibiting PRMT5 (IC50=0.107 μM), thereby protecting normal cells with wild-type MTAP[1][2]. | [in vivo]
AMG 193 (3-100 mg/kg; p.o.; once every 5 days for 4 doses) dose-dependently inhibits tumor growth in MTAP-deficient xenograft mice[2].
AMG 193 (100 mg/kg; p.o.; once daily for 11 days) slightly reduces body weight in mice implanted with DLBCL (DOHH-2) tumors and causes tumor regression in 70% of mice, with preservation of normal hematopoietic cell lineages[2]. | Animal Model: | HCT116 MTAP-deficient mice[2] | | Dosage: | 3、10、30、100 mg/kg | | Administration: | p.o.; The drug was administered on day 20 after mice were implanted with DLBCL (DOHH-2) tumor cells and was administered once every 5 days for a total of 4 doses. | | Result: | Inhibited SDMA signaling in mtap-deleted tumors at all doses. |
| Animal Model: | Mice implanted with DLBCL (DOHH-2) tumors[2] | | Dosage: | 100 mg/kg | | Administration: | p.o.; Once daily for 11 days | | Result: | Caused a significant increase in the Sub-G1 population and induced tumor cell death. |
| [References]
[1] Belmontes B, et al. Abstract B177: The discovery and preclinical characterization of AMG 193, a first-in-class MTA-cooperative PRMT5 inhibitor with broad activity against MTAP-null cancers[J]. Molecular Cancer Therapeutics, 2023, 22(12_Supplement): B177-B177.
[2] Belmontes B, et al. AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers[J]. Cancer Discovery, 2024: OF1-OF23. DOI:10.1158/2159-8290.CD-24-0887 |
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