1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro-
1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro- Basic information
- Product Name:
- 1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro-
- Synonyms:
-
- 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-3-fluoro-1-naphthonitrile
- MRTX 9768
- SDMA,toxicity,glioblastoma,orally,MRTX9768,low,Inhibitor,hematological,MRTX-9768,MTAP,CDKN2A,MRTX 9768,inhibit,Histone Methyltransferase,anticancer,PRMT5-MTA
- 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-3-fluoro-1-naphthonitrile - [AC80900]
- 1-Naphthalenecarbonitrile, 2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-3-fluoro-
- CAS:
- 2629314-68-5
- MF:
- C24H17FN6O
- MW:
- 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- Chemical Properties
- 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- Usage And Synthesis
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-Supplier
- Tel
- 18149758185
- sales-cpd@caerulumpharma.com
- Tel
- 021-QQ：65489617 15618227136
- Sales@ATKchemical.com
- Tel
- +1-781-999-5354; +17819995354
- marketing@targetmol.com
- Tel
- 17625585511
- 1580084073@qq.com
- Tel
- 18051384581
- sales@chemhifuture.com