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| | Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- Basic information |
| Product Name: | Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- | | Synonyms: | Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]-;(S)-(4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)(3-(4-(trifluoromethyl)phenyl)morpholino)methanone;8-[(3S)-3-[4-(trifluoromethyl)phenyl]morpholine-4-carbonyl]-1H,3H-furo[3,4-c]1,7-naphthyridin-4-amine;MTA-cooperative PRMT5 inhibitor AMG-193 | | CAS: | 2790567-82-5 | | MF: | C22H19F3N4O3 | | MW: | 444.41 | | EINECS: | | | Product Categories: | APIS | | Mol File: | 2790567-82-5.mol | ![Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- Structure](CAS/20210305/GIF/2790567-82-5.gif) |
| | Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- Chemical Properties |
| Boiling point | 670.0±55.0 °C(Predicted) | | density | 1.451±0.06 g/cm3(Predicted) | | pka | 5.22±0.20(Predicted) | | form | Solid | | color | White to light yellow | | InChIKey | BFEBTMFPRJPBTK-LJQANCHMSA-N | | SMILES | C(C1=NC=C2C(=C1)C1COCC=1C(N)=N2)(N1CCOC[C@@H]1C1=CC=C(C(F)(F)F)C=C1)=O |
| | Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- Usage And Synthesis |
| 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 |
| | Methanone, (4-amino-1,3-dihydrofuro[3,4-c][1,7]naphthyridin-8-yl)[(3S)-3-[4-(trifluoromethyl)phenyl]-4-morpholinyl]- Preparation Products And Raw materials |
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