1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro-
- Product Name
- 1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro-
- CAS No.
- 2629314-68-5
- Chemical Name
- 1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro-
- Synonyms
- MRTX 9768;2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-3-fluoro-1-naphthonitrile;1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro-;2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-3-fluoro-1-naphthonitrile - [AC80900];SDMA,toxicity,glioblastoma,orally,MRTX9768,low,Inhibitor,hematological,MRTX-9768,MTAP,CDKN2A,MRTX 9768,inhibit,Histone Methyltransferase,anticancer,PRMT5-MTA
- CBNumber
- CB28992743
- Molecular Formula
- C24H17FN6O
- Formula Weight
- 424.43
- MOL File
- 2629314-68-5.mol
1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro- Property
- 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)
- pka
- 11.36±0.40(Predicted)
- form
- Solid
- 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
1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro- Chemical Properties,Usage,Production
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
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.
1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro- Preparation Products And Raw materials
Raw materials
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