1. Epigenetics Apoptosis NF-κB
  2. METTL3 Apoptosis MDM-2/p53 NF-κB Caspase
  3. RSM3

RSM3 is a METTL3-METTL14 complex inhibitor with a Kd of 3.10 μM for the METTL3-METTL14 complex. RSM3 reduces the m6A modification level of SLC31A1 and the global RNA methylation level. RSM3 upregulates programmed cell death-related genes, enhances cell apoptosis, inhibits pro-cancer signals and suppresses tumor growth. RSM3 is applicable to the research of preeclampsia and cancer.

For research use only. We do not sell to patients.

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RSM3

RSM3 Chemical Structure

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Based on 1 publication(s) in Google Scholar

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Description

RSM3 is a METTL3-METTL14 complex inhibitor with a Kd of 3.10 μM for the METTL3-METTL14 complex. RSM3 reduces the m6A modification level of SLC31A1 and the global RNA methylation level. RSM3 upregulates programmed cell death-related genes, enhances cell apoptosis, inhibits pro-cancer signals and suppresses tumor growth. RSM3 is applicable to the research of preeclampsia and cancer[1][2].

In Vitro

RSM3 inhibits the methyltransferase activity of the purified METTL3-METTL14 complex by 45.5%[1].
RSM3 inhibits the viability of CCRF-CEM leukemia cells with an IC50 of 4.6 μM[1].
RSM3 inhibits the viability of DU145 prostate cancer cells with an IC50 of 25.8 μM[1].
RSM3 inhibits the viability of ASPC-1 pancreatic cancer cells with an IC50 of 33.8 μM[1].
RSM3 inhibits the viability of PC3 prostate cancer cells with an IC50 of 26.5 μM[1].
RSM3 (15 μM; 24 h) reduces the migratory capacity of PC3 and DU145 prostate cancer cells[1].
RSM3 (15 μM) induces G1 phase cell cycle arrest and apoptosis in PC3 and DU145 prostate cancer cells[1].
RSM3 (25 μM; 12 h) reduces the protein levels of METTL3 and METTL14 in PC3 prostate cancer cells[1].
RSM3 (25 μM; 12 h) inhibits the activity of the ERK/MAPK signaling pathway in PC3 prostate cancer cells by reducing the phosphorylation level of p42/44[1].
RSM3 (12 h) reduces the global RNA m6A modification level in PC3 and DU145 prostate cancer cells[1].
RSM3 (25 μM; 12 h) induces a specific transcriptomic response in PC3 prostate cancer cells, upregulating programmed cell death, p53 signaling pathway, differentiation and immune pathways, while downregulating cancer proliferation and cell cycle pathways, and enriching gene signatures of apoptosis, p53 and AR pathways[1].
RSM3 (25 μM; 12 h) upregulates NF-κB, inflammation, apoptosis and luminal differentiation-related genes, and downregulates cell cycle, proliferation and stemness-related genes in PC3 prostate cancer cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Migration Assay [1]

Cell Line: PC3 and DU145 (prostate cancer) cells
Concentration: 15 μM
Incubation Time: 24 h
Result: Resulted in approximately a 2-3 fold reduction in cell migration in PC3 and DU145 cells.

Western Blot Analysis[1]

Cell Line: PC3 (prostate cancer) cells
Concentration: 25 μM
Incubation Time: 12 h
Result: Reduced the protein levels of METTL3 and METTL14 in PC3 cells.\n
Reduced phosphorylation levels of p42/44 (ERK1/2).

Real Time qPCR[1]

Cell Line: PC3 (prostate cancer) cells
Concentration: 25 μM
Incubation Time: 12 h
Result: Upregulated NF-kB responsive, inflammatory, apoptosis, and luminal differentiation (AR, PSA, NKX3.1, CK18) genes, and downregulated cell cycle, proliferation, and stemness genes.
In Vivo

RSM3 (50 mg/kg; i.p.; single administration) shows no obvious acute toxicity in C57BL/6 mice[1].
RSM3 (20 mg/kg; peritumoral injection; once every 2 days; for 14 consecutive days) inhibits the growth of PC3/ASPC-1 xenografts in mice[1].
RSM3 (50 mg/kg; intraperitoneal injection; daily; day 10-20) significantly improves preeclampsia (PE)-related symptoms in rats[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Immunocompromised mice treated PC3 cells (xenograft model)[1]
Dosage: 20 mg/kg
Administration: peri-tumoral injection; every 2 days; 14 days
Result: Reduced tumor volumes, average tumor mass.
Decreased METTL3 expression and global m6A levels in tumor tissue.
Increased Caspase-3 expression, decreased Ki67 expression in tumor tissue.
Showed no significant changes in body weight.
Detected no histopathological abnormalities in heart, liver, spleen, lung, or kidney tissue.
Animal Model: Immunocompromised mice treated ASPC-1 cells (xenograft model)[1]
Dosage: 20 mg/kg
Administration: peri-tumoral injection; every 2 days; 14 days
Result: Reduced tumor volume.
Lowered average tumor mass.
Animal Model: Sprague-Dawley (SD) (female, 7-week-old, 200-220 g, PE model)[2]
Dosage: 50 mg/kg
Administration: i.p.; daily; GD 10 to GD 20
Result: Significantly reduced systolic blood pressure.
Significantly reduced 24-hour urine protein concentration.
Significantly reduced urine albumin to creatinine ratio.
Significantly lowered placental METTL3 protein expression.
Significantly increased placental SLC31A1 protein expression.
Significantly reduced m6A modification level of SLC31A1 in placental tissue.
Molecular Weight

3049.66

Formula

C130H218N54O26S3

Appearance

Solid

Color

White to off-white

Sequence

Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Cys-Met-Glu-Leu-Gly-Arg-Glu-Cys-Leu-Asn-Leu-Trp-NH2 (Stapled between two Cys via bhp)

Sequence Shortening

RRRRRRRRRCMELGRECLNLW-NH2 (Stapled between two Cys via bhp)

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Sealed storage, away from moisture

Powder -80°C 2 years
-20°C 1 year

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

H2O : ≥ 25 mg/mL (8.20 mM)

DMSO : 25 mg/mL (8.20 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 0.3279 mL 1.6395 mL 3.2791 mL
5 mM 0.0656 mL 0.3279 mL 0.6558 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
H2O / DMSO 1 mM 0.3279 mL 1.6395 mL 3.2791 mL 8.1976 mL
5 mM 0.0656 mL 0.3279 mL 0.6558 mL 1.6395 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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RSM3
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