MRTX-1719

MRTX-1719 is an inhibitor of the protein arginine methyltransferase 5 (PRMT5) and methylthioadenosine (MTA) complex. It selectively binds to the PRMT5/MTA complex over the PRMT5 and S-adenosyl-L-methionine (SAM) complex (Kds = 0.14 and 9.4 pM, respectively). MRTX-1719 selectively decreases protein dimethylarginine methylation levels in MTAP-/- HCT116 colon cancer cells, which lack methylthioadenosine phosphorylase (MTAP, IC50 = 8 nM), over wild-type HCT116 cells (IC50 = 653 nM), as well as selectively reduces the viability of MTAP-/- HCT116 cells (IC50 = 12 nM) over wild-type HCT116 cells (IC50 = 890 nM). In vivo, MRTX-1719 (12.5-100 mg/kg per day) reduces tumor volume in an MTAP-/- Lu-99 lung cancer mouse xenograft model.Formal Name: (2R)-2-[4-[4-(aminomethyl)-1,2-dihydro-1-oxo-6-phthalazinyl]-1-methyl-1H-pyrazol-5-yl]-4-chloro-6-(cyclopropyloxy)-3-fluoro-benzonitrile. CAS Number: 2630904-45-7. Synonyms: (M)-27. Molecular Formula: C23H18ClFN6O2. Formula Weight: 464.9. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Soluble, DMSO: Soluble. SMILES: O=C1C(C=CC(C2=[C@]([C@]3=C(C#N)C(OC4CC4)=CC(Cl)=C3F)N(N=C2)C)=C5)=C5C(CN)=NN1. InChi Code: InChI=1S/C23H18ClFN6O2/c1-31-22(20-15(8-26)19(33-12-3-4-12)7-17(24)21(20)25)16(10-28-31)11-2-5-13-14(6-11)18(9-27)29-30-23(13)32/h2,5-7,10,12H,3-4,9,27H2,1H3,(H,30,32). InChi Key: BZKIOORWZAXIBA-UHFFFAOYSA-N.