SGC707 is a potent and selective PRMT3 inhibitor with IC50 value of 31nM. SGC707 stabilized PRMT3 in both HEK293 and A549 cells with EC50 values of 1.3μm and 1.6μm in PRMT3 InCELL Hunter Assays. It reduced PRMT3-dependent H4R3me2a in dose-dependent manner[3]. Chronic treatment with SGC707, i.p., 3 times per week, developed less severe hepatic steatosis as exemplified by the 51% reduced liver triglyceride levels and led a body weight loss by 94% of 12-week old hyperlipidemic apolipoprotein E knockout mice mice fed a Western-type diet for six weeks to induce both hepatic steatosis and atherosclerosis. This may due to the inhibition of PRMT3 uncoupling two transcriptional pathways, of both cholesterol metabolism and hepatic lipogenesis, in vivo by acting as a specific lipogenic coactivator of LXR[4].
作用机制
SGC707 binds an allosteric site at the interface of the two PRMT3 subunits that is distant from the site of methyl transfer.[3]
SGC707 细胞实验
Cell Line
Concentration
Treated Time
Description
References
GSC262 cells
10 µM
Inhibited GSC cell growth
Cell Death Dis. 2022 Nov 9;13(11):943.
A549
1.6 µM (EC50)
Stabilized PRMT3 with EC50 of 1.6 μM
Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5166-70.
HEK293
1.3 µM (EC50)
Stabilized PRMT3 with EC50 of 1.3 μM
Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5166-70.
GSC28 cells
10 µM
Inhibited GSC cell growth
Cell Death Dis. 2022 Nov 9;13(11):943.
U87 cells
10 µM
Inhibited GBM cell growth
Cell Death Dis. 2022 Nov 9;13(11):943.
U251 cells
10 µM
Inhibited GBM cell growth
Cell Death Dis. 2022 Nov 9;13(11):943.
HMO6 cells
10 µM
No effect on normal brain cell growth
Cell Death Dis. 2022 Nov 9;13(11):943.
MOLT4 cells
10 µM
24 hours
Evaluate PRMT3 degradation effect, 11 significantly degraded PRMT3 protein
Adv Sci (Weinh). 2024 Oct;11(38):e2405963.
MOLM13 cells
10 µM
24 hours
Evaluate PRMT3 degradation effect, 11 significantly degraded PRMT3 protein
Adv Sci (Weinh). 2024 Oct;11(38):e2405963.
MV-4-11 cells
10 µM
24 hours
Evaluate PRMT3 degradation effect, 11 significantly degraded PRMT3 protein
Adv Sci (Weinh). 2024 Oct;11(38):e2405963.
RS4;11 cells
10 µM
24 hours
Evaluate PRMT3 degradation effect, 11 significantly degraded PRMT3 protein
Adv Sci (Weinh). 2024 Oct;11(38):e2405963.
Huh7 cells
1 µM
48 hours
Inhibited PRMT3-mediated LDHA methylation, reduced glucose consumption and lactate production
Clin Transl Med. 2022 Jan;12(1):e686.
SNU398 cells
1 µM
48 hours
Inhibited PRMT3-mediated LDHA methylation, reduced glucose consumption and lactate production
Clin Transl Med. 2022 Jan;12(1):e686.
Human mesenchymal stem cells (hMSCs)
10 µM
96 hours
SGC707 significantly inhibited the osteogenic differentiation ability of hMSCs, as evidenced by reduced ALP activity and calcium deposition.
Cell Death Dis. 2019 Aug 5;10(8):581.
HEB cells
10 µM
No effect on normal brain cell growth
Cell Death Dis. 2022 Nov 9;13(11):943.
SGC707 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
LDL receptor knockout mice
Atherogenic Western-type diet-fed model
Intraperitoneal injection
0.3 mg per injection, approximately 10 mg/kg
3 times per week for 3 weeks
To investigate the effect of SGC707 on hepatic steatosis and plasma triglyceride levels. Results showed that SGC707 treatment reduced liver triglyceride stores by 50% and plasma triglyceride levels by 32%, but induced pruritus and skin lesions.
Sci Rep. 2022 Jan 10;12(1):483
NOG-dKO mice
CDX and PDX models
Intraperitoneal injection
10 mg/kg
Every 2 days until the end of the study
SGC707 combined with anti-PD-1 therapy showed more potent antitumor effects.
Adv Sci (Weinh). 2023 Dec;10(36):e2303812
C57BL/6 mice
Chronic kidney disease (CKD) model
Intraperitoneal injection
10 mg/kg
For 10 weeks
To investigate the effect of SGC707 on vascular calcification in CKD mice. Results showed that SGC707 alleviated CKD-induced vascular calcification and renal injury.
Mol Med. 2024 Jan 10;30(1):8
C57BL/6 mice
T0901317 and palm oil-induced hepatic steatosis model
Intraperitoneal injection
10 or 30 mg/kg
Three injections over 4 days
To evaluate the effect of PRMT3 inhibition on LXR-mediated hepatic lipogenesis. Results showed that SGC707 treatment significantly reduced hepatic lipogenic gene expression and liver triglyceride content.
Br J Pharmacol. 2018 Aug;175(15):3175-3183
Mice
Osteoporosis model
Subcutaneous implantation of ALZET pump
20 mg/kg/day
Continuous for 6 weeks
SGC707 treatment resulted in bone loss in mice, characterized by reduced bone density and trabecular number.
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