MS023 is a potent, selective, and cell-active inhibitor of human type I PRMTs with IC50 values of 30, 119, 83, 4 and 5nM for PRMT1, 3, 4, 6 and 8, respectively. MS023 inhibited both PRMT1 methyltransferase activity shown by decreased level of H4R3me2a post 48h in MCF7 cells, and PRMT6 methyltransferase activity shown by decreased level of H4R3me2a post 20h in HEK293 cells at concentration>37nM. Treatment with MS023 at 10μM or 50μM for 2 days led a significant decrease in global levels of arginine asymmetric dimethylation (Rme2a) and a concurrent increase in global levels of arginine monomethylation (Rme1) and arginine symmetric demethylation in MCF7 and HEK293 cells[2].
作用机制
MS023 can effectively occupy the arginine side chain binding pocket of the substrate and likely form the substrate-inhibitor-PRMT6 complex without significant penalty of free energy.[2]
MS023 细胞实验
Cell Line
Concentration
Treated Time
Description
References
786-0
5 µM
7 days
To validate MS023’s on-target activity, a global downregulation of aDMA species was observed.
Nat Commun. 2024 Sep 19;15(1):8232.
RCC243
5 µM
7 days
To validate MS023’s on-target activity, a global downregulation of aDMA species was observed.
Nat Commun. 2024 Sep 19;15(1):8232.
Hs578-T
1 μM
5 days
MS023 treatment did not significantly affect cell growth
MS023 treatment dose-dependently increased SMN2 exon 7 inclusion and protein levels.
EMBO Mol Med. 2023 Nov 8;15(11):e17683.
SMA type II patient-derived fibroblasts
1-10 µM
48 h
MS023 treatment increased SMN2 exon 7 inclusion and elevated SMN protein levels up to 1.6-fold.
EMBO Mol Med. 2023 Nov 8;15(11):e17683.
A549 cells
1 μM
24 h
To study the inhibitory effect of C-MS023 on histone arginine asymmetric dimethylation, results showed that C-MS023 had a weak influence on H3R2me2a and H4R3me2a marks at 1 μM, but significantly downregulated these marks after 420 nm light irradiation.
J Med Chem. 2025 Feb 27;68(4):4373-4381.
A549 cells
0.1 μM
24 h
To study the inhibitory effect of MS023 on histone arginine asymmetric dimethylation, results showed that MS023 significantly reduced the levels of H3R2me2a and H4R3me2a marks.
J Med Chem. 2025 Feb 27;68(4):4373-4381.
HCT-116
20 µM
5 days
MS023 had minimal effect on ALP activity but significantly reduced cell proliferation in HCT-116 cells.
Sci Rep. 2020 Nov 18;10(1):20030.
HT-29
5 µM
5 days
MS023 significantly increased ALP activity and delayed cell proliferation in HT-29 cells.
Sci Rep. 2020 Nov 18;10(1):20030.
K562 cells
1 μM
4 days
MS023 treatment significantly reduced H3R2me2a modification levels and increased γ-globin expression, partially rescuing the erythroid differentiation defects caused by the GATA1 Leu387fs mutation.
Haematologica. 2024 Sep 1;109(9):2955-2968.
MS023 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL6/J mice
Wild-type
Intraperitoneal injection
80 mg/kg
Every other day for one month
To evaluate the effect of MS023 on megakaryocyte differentiation and platelet production, results showed that MS023 increased the number of high polyploid megakaryocytes and platelets.
Cell Rep. 2021 Jul 27;36(4):109421.
Mice
CcRCC xenograft models
Intraperitoneal injection
80 mg/kg
3 days on/4 days off, for 3 weeks
To evaluate the antitumor activity of MS023 in ccRCC xenograft models, significant inhibition of tumor growth was observed.
Nat Commun. 2024 Sep 19;15(1):8232.
Mice
Myocardial infarction model
Intraperitoneal injection
80 mg/kg
Every 3 days, starting from 3 days before surgery
Pretreatment with MS023 significantly improved cardiac function and reduced fibrosis in Hdc/C0//C0 mice after myocardial infarction
Acta Pharm Sin B. 2022 Apr;12(4):1840-1855
Mice
CML mouse model
Intraperitoneal injection
80 mg/kg
Once daily for 2 weeks
MS023 significantly prolonged the survival of CML mice, alleviated splenomegaly, and markedly reduced the leukemia burden and the proportions of LSPCs, with minimal impact on normal hematopoiesis.
Adv Sci (Weinh). 2025 Feb;12(5):e2308586
Mice
MDA-MB-468 xenograft model
Intraperitoneal injection
60 mg/kg
Once daily for 5 weeks
MS023 significantly reduced tumor growth and final tumor weight
Nat Chem Biol. 2022 Aug;18(8):821-830.
Mice
SMA mouse model
Oral
2 mg/kg
Daily, from P0 to endpoint
MS023 treatment significantly increased the survival rate of SMA mice and improved disease-associated weight loss.
EMBO Mol Med. 2023 Nov 8;15(11):e17683.
Nude mice
HT-29 xenograft model
Intraperitoneal injection
15 mg/kg and 30 mg/kg
Twice a week for 19 days
MS023 significantly delayed the growth of HT-29 xenograft tumors and reduced tumor cell proliferation.
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