| Identification | Back Directory | [Name]
INDEX NAME NOT YET ASSIGNED | [CAS]
2629314-68-5 | [Synonyms]
MRTX 9768
2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-3-fluoro-1-naphthonitrile | [Molecular Formula]
C24H17FN6O | [MDL Number]
MFCD34473210 | [MOL File]
2629314-68-5.mol | [Molecular Weight]
424.43 |
| Chemical Properties | Back Directory | [density ]
1.44±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C, protect from light | [solubility ]
DMSO : 30 mg/mL (70.68 mM; ultrasonic and warming and heat to 60°C) | [form ]
Solid | [pka]
11.36±0.40(Predicted) | [color ]
White to light brown | [InChI]
InChI=1S/C24H17FN6O/c1-31-23(22-18(10-26)15-5-3-2-4-13(15)9-20(22)25)19(12-28-31)14-6-7-16-17(8-14)21(11-27)29-30-24(16)32/h2-9,12H,11,27H2,1H3,(H,30,32) | [InChIKey]
BPTYWAYMKBEXES-UHFFFAOYSA-N | [SMILES]
C1(C#N)=C2C(C=CC=C2)=CC(F)=C1C1N(C)N=CC=1C1C=CC2=C(C=1)C(CN)=NNC2=O |
| Hazard Information | Back Directory | [Uses]
MRTX9768 is a potent, selective, orally active, first-in-class PRMT5-MTA complex inhibitor[1]. | [Biological Activity]
MRTX9768 is a potent, orally active PRMT5 inhibitor. MRTX9768 is a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors[1].
MRTX9768 inhibits SDMA and cell proliferation in HCT116 MTAP-del cells (SDMA IC50 3 nM; prolif. IC50 11 nM) with marked selectivity over HCT116 MTAP-WT cells (SDMA IC50 544 nM; prolif. IC50 861 nM)[1].
In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors[1]. | [in vivo]
In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow[1].
MRTX9768 selectively targets MTAP/CDKN2A-deleted tumors (such as glioblastoma)[1][2].
MRTX9768 (PO dose 30 mg/kg in CD-1 mouse and beagle dog, 10 mg/kg in cynomolgus monkey) has a favorable ADME profile (>50% bioavailability in mice and dogs, moderate to high clearance, No changes in RBC parameters when administered well above efficacious concentrations (1000 mg/kg))[3].
MRTX9768 (100 mg/kg, orally, BID, 6/21 days) results in SDMA inhibition maintaining 3 days after dosing is stopped[3].
| [IC 50]
PRMT5 | [storage]
-20°C, protect from light | [References]
[1]. Christopher R. et al. Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB003. |
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