Uses
MS023 is a potent inihbitor of PRMTs 1,3,4,6,and 8 (IC50 = 30, 119, 83, 8, and 8 nM, respectively), which are responsible for asymmetric dimethylation of arginine residues.
Biological Activity
ms023 is a type i prmts inhibitor.protein arginine methyltransferases (prmts) play a critical role in various biological processes. prmt overexpression has been observed in a variety of human diseases including cancer. prmts has been divided into three categories: type i prmts for catalyzing mono- and asymmetric dimethylation of arginine residues, type ii prmts for catalyzing mono- and symmetric dimethylation of arginine residues, and type iii prmt for catalyzing only monomethylation of arginine residues.
Biochem/physiol Actions
MS023 is a potent and selective chemical probe for Type I protein arginine methyltransferases (PRMTs). MS023 is a potent inihbitor of PRMTs 1,3,4,6,and 8 (IC50 = 30, 119, 83, 8, and 8 nM, respectively), which are responsible for asymmetric dimethylation of arginine residues. MS023 is active in cells. For full characterization details, please visit the MS023 probe summary on the Structural Genomics Consortium (SGC) website.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
in vitro
previous study showed that ms023 had excellent potency for type i prmts but was completely inactive to both type ii and type iii prmts, protein lysine methyltransferases as well as dna methyltransferases. moreover, the crystal structure of prmt6 with ms023 indicated that ms023 bound to the substrate binding site. in addition, ms023 could potently decrease the cellular levels of histone arginine asymmetric dimethylation. furthermore, ms023 could reduce the levels of arginine asymmetric dimethylation and could also concurrently increase the cellular levels of both arginine monomethylation and symmetric dimethylation [1].
in vivo
Administration of MS023 (160 mg/kg, i.p) in combination with PKC412 (100 mg/kg, i.g.) blocks MLL-r acute lymphoblastic leukemia (ALL) propagation by inhibiting maintenance of functional MLL-r ALL-initiating cells[2].
| Animal Model: | NOD-scid IL2Rgnull (NSG) mice bearing primary MLL-r ALL cells[2] |
| Dosage: | 160 mg/kg |
| Administration: | Intraperitoneal injection; PKC412 (100 mg/kg, i.g.), MS023 (160 mg/kg, i.p), or a combination for 4 weeks |
| Result: | Combinatorial treatment extended survival of leukemic mice relative to single treatments. |
IC 50
30, 119, 83, 4, and 5 nm for prmt1, prmt3, prmt4, prmt6 and prmt8, respectively.
