STM2457 is an inhibitor of methyltransferase-like 3 (METTL3) and METTL14 complex with IC50 value of 16.9 µM [1]. It inhibits the growth of a panel of acute myeloid leukemia (AML) cell lines (IC50 = 0.6-10.3 µM). STM2457 also inhibits the proliferation, migration and invasion of HuCC-T1 and HCCC-9810 intrahepatic cholangiocarcinoma cells (ICC) in a concentration-dependent manner [2]. When administered at a dose of 50 mg/kg, it increases survival in a patient-derived xenograft (PDX) mouse model of AML [1].
STM2457 细胞实验
Cell Line
Concentration
Treated Time
Description
References
THP-1
0.04-50 μM
72 h
To study the anti-leukaemic potential of STM2457 in the AML cell line THP-1, results showed that STM2457 significantly reduced cell proliferation.
Nature. 2021 May;593(7860):597-601.
MOLM-13
1 μM
24 h
To study the anti-leukaemic potential of STM2457 in the AML cell line MOLM-13, results showed that STM2457 significantly reduced cell proliferation and decreased m6A levels.
Nature. 2021 May;593(7860):597-601.
TM4 cells
20 μM
24 h
To verify the m6A-dependent reduction of Wt1 stability under environmental stress
Nat Commun. 2024 Feb 14;15(1):1353.
BMDMs
10 μM
7 days
STM2457 inhibited TGF-β1-induced MMT, reducing the expression of Smad3, α-SMA, and Col-I
Adv Sci (Weinh). 2025 Mar;12(11):e2412123.
H446DDP
6.25 μM
24 h
STM2457 significantly reduced the IC50 values of CDDP and VP16 in H446DDP cells and increased the proportion of apoptotic cells.
J Exp Clin Cancer Res. 2023 Mar 17;42(1):65.
H69AR
6.25 μM
24 h
STM2457 significantly reduced the IC50 values of CDDP and VP16 in H69AR cells and increased the proportion of apoptotic cells.
J Exp Clin Cancer Res. 2023 Mar 17;42(1):65.
human lymphatic endothelial cells (HLECs)
1 μM
24 h
To evaluate the effects of STM2457 on HLEC proliferation, migration, and tube formation, results showed that STM2457 significantly inhibited these functions
MedComm (2020). 2024 Oct 4;5(10):e728.
human lymphatic endothelial cells (HLECs)
1 μM
24 h
To evaluate the cytotoxicity of STM2457 on HLECs, results showed no obvious cytotoxicity at 1 μM
MedComm (2020). 2024 Oct 4;5(10):e728.
HL-1 cardiomyocytes
5 μM
24 h
To evaluate the effect of STM2457 on DOX-induced cardiomyocyte ferroptosis, results showed that STM2457 significantly inhibited DOX-induced cell death and LDH release, reduced lipid peroxidation and MDA production, and improved GSH/GSSG ratio.
Redox Biol. 2024 Jun;72:103157.
STM2457 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c nude mice
Subcutaneous tumor model
Intraperitoneal injection
50 mg/kg STM2457
Once daily for 14 days
To evaluate the effect of METTL3 inhibitor combined with anti-PD-1 therapy
Int J Biol Sci. 2022 Jun 3;18(9):3874-3887
Mice
AML PDX models
Intraperitoneal injection
50 mg/kg
Once daily for two weeks
To study the anti-leukaemic effect of STM2457 in AML PDX models, results showed that STM2457 significantly prolonged the lifespan of mice and reduced AML engraftment and expansion.
Nature. 2021 May;593(7860):597-601.
Mice
Orthotopic colorectal cancer model
Intratumoral injection
50 mg/kg
Single injection
To evaluate the effect of GOSM-gel on NK cell infiltration in the orthotopic colorectal cancer model
Bioact Mater. 2024 Oct 22;44:236-255
Mice
High-fat diet-induced obesity model
Local testicular injection
50.0 mg/kg
Once a week for 5 weeks
To restore the sperm count and Wt1 levels reduced by high-fat diet
Nat Commun. 2024 Feb 14;15(1):1353.
Mice
NAFLD-HCC model
Intraperitoneal injection
50mg/mice
Every other day, ongoing treatment
To evaluate the efficacy of STM2457 in combination with anti-PD-1 therapy for NAFLD-HCC. Single STM2457 significantly inhibited tumor growth, while the combination of STM2457 and anti-PD-1 showed stronger tumor suppression and significantly increased intratumoral infiltration of IFN-γ+ and GZMB+ CD8+ T cells.
Cell Rep Med. 2023 Aug 15;4(8):101144
Nude mice
H69AR xenograft model
Subcutaneous injection
6.25 μM
Single dose, continuous observation of tumor growth
STM2457 significantly inhibited the growth of H69AR xenografts and reduced the tumor volume after chemotherapy.
J Exp Clin Cancer Res. 2023 Mar 17;42(1):65.
Mice
Neuroblastoma xenograft model
Intraperitoneal injection
50 mg/kg
Once daily for 12 days
To evaluate the efficacy of STM2457 in NB treatment, the results showed that STM2457 combined with VCR significantly inhibited tumor growth.
J Exp Clin Cancer Res. 2024 May 14;43(1):141
C57BL/6 mice
Corneal suture model
Subconjunctival injection
1 μM
7 days
To evaluate the effects of STM2457 on pathological lymphangiogenesis, results showed that STM2457 significantly inhibited lymphangiogenesis in the corneal suture model
MedComm (2020). 2024 Oct 4;5(10):e728.
Mice
Chronic DOX-induced cardiomyopathy model
Intraperitoneal injection
50 mg/kg
Once daily for 4 weeks
To evaluate the effect of STM2457 on DOX-induced cardiomyopathy, results showed that STM2457 significantly improved DOX-induced cardiac dysfunction, fibrosis, and iron accumulation, and alleviated cardiomyocyte ferroptosis.
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