RMC-4998
Based on 1 Customer Validation
RMC-4998 is an orally active inhibitor targeting the active or GTP-bound state of the KRASG12C mutant. RMC-4998 can form a ternary complex with intracellular CYPA and the activated KRASG12C mutant, with an IC50 value of 28 nM. RMC-4998 can inhibit ERK signaling in KRASG12C mutant cancer cells and induce apoptosis. RMC-4998 can be used for tumor research.
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- Purity: 99.31%
- CAS No.: 2642037-07-6
- 화학식: C57H74N8O7
- 분자량:983.25
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보관:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
KRASG12C[1].
RMC-4998 (100 nM, 120 h) disrupts oncogenic signaling in KRASG12C mutant cells by recruiting cyclophilin A (CYPA) to the active state of mutant KRAS[1]. RMC-4998 can inhibit the expression of ERK signaling related proteins and cell proliferation in KRASG12C mutant cancer cells[1]. RMC-4998 (0-1000 nM, 72 h) inhibits lung cancer cell viability by suppressing the PI3K/mTOR and ERK signaling pathways[2]. RMC-4998 (30 nM, 96 h) can inhibit ERK protein phosphorylation and suppress LU65 cell viability[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KRASG12C mutant cancer cell LU65 and H358 models
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Concentration:100 nM
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Incubation Time:120 h
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Result:Inhibited cell proliferation, with an IC50 value of 0.28 nM.
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Cell Line:KRASG12C mutant cancer cell models (H358, H23, H2030, SW873, MIA PaCa-2)
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Concentration:0-10000 nM
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Incubation Time:2 h
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Result:Inhibited phosphorylation of ERK signaling related proteins, including PSK, ERK, and CRAF proteins.
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Cell Line:H358, LU65, H2122, LU99A, SW1573 cells
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Concentration:0-1000 nM
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Incubation Time:72 h
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Result:Had the strongest inhibitory effect on H358, LU65, and H2122 cells, but its effect was weaker in cell lines that are most resistant to inactive KRASG12C inhibitors such as LU99A and SW1573.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Mice model bearing H358 CDX tumors[1].
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Dosage:10-200 mg/kg
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Administration:Oral gavage (p.o.); once daily; 28 days
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Result:Inhibited ERK phosphorylation in tumors for about 24 hours and induced cell apoptosis, leading to tumor regression.
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Animal Model:The cell-line derived H2122 KRASG12C lung adenocarcinoma xenograft model (CDX)[2].
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Dosage:80 mg/kg
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Administration:Oral gavage (p.o.); once daily; 4 weeks
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Result:Inhibited tumor growth for 30-35 days.
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Animal Model:Sotorasib-R LU65 mice xenograft model[3].
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Dosage:100 mg/kg
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Administration:Oral gavage (p.o.); once dailys
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Result:Reduced tumor volume and lowered the expression of pERK protein in the tumor.
Chemical Information
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CAS No. 2642037-07-6
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Appearance Solid
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분자량 983.25
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화학식 C57H74N8O7
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Color Off-white to light yellow
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SMILES
O=C(N1CCC[C@@H](C2=O)N1)[C@@H](NC([C@H](C(C)C)N3C([C@@]4(CCN(C(C#CC(C)(C)N(C)C)=O)C4)CC3)=O)=O)CC5=CC(C6=CC(C(CC(C)(C)CO2)=[C@@]([C@@]7=C([C@H](C)OC)N=CC=C7)N8CC)=C8C=C6)=CC=C5
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선적
Room temperature in continental US; may vary elsewhere.
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보관
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
용액&용해도
DMSO : 100 mg/mL (101.70 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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 (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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 (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.54 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Schulze CJ, et al. Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS. Science. 2023 Aug 18;381(6659):794-799. [Content Brief]
[2]. Kitai H,et al. Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer. Nat Commun. 2024 Jul 19;15(1):6076. [Content Brief]
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 (stored under nitrogen). 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0170 mL | 5.0852 mL | 10.1704 mL | 25.4259 mL |
| 5 mM | 0.2034 mL | 1.0170 mL | 2.0341 mL | 5.0852 mL | |
| 10 mM | 0.1017 mL | 0.5085 mL | 1.0170 mL | 2.5426 mL | |
| 15 mM | 0.0678 mL | 0.3390 mL | 0.6780 mL | 1.6951 mL | |
| 20 mM | 0.0509 mL | 0.2543 mL | 0.5085 mL | 1.2713 mL | |
| 25 mM | 0.0407 mL | 0.2034 mL | 0.4068 mL | 1.0170 mL | |
| 30 mM | 0.0339 mL | 0.1695 mL | 0.3390 mL | 0.8475 mL | |
| 40 mM | 0.0254 mL | 0.1271 mL | 0.2543 mL | 0.6356 mL | |
| 50 mM | 0.0203 mL | 0.1017 mL | 0.2034 mL | 0.5085 mL | |
| 60 mM | 0.0170 mL | 0.0848 mL | 0.1695 mL | 0.4238 mL | |
| 80 mM | 0.0127 mL | 0.0636 mL | 0.1271 mL | 0.3178 mL | |
| 100 mM | 0.0102 mL | 0.0509 mL | 0.1017 mL | 0.2543 mL |
RMC-4998 Related Classifications
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