| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
RMC-0331 targets SOS1 (Son of Sevenless 1), a guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP on RAS proteins. RAS proteins are small GTPases that are frequently mutated in cancer and act as molecular switches in cell signaling. By binding to SOS1, RMC-0331 disrupts the RAS-SOS1 interaction, preventing the activation of RAS and thereby blocking downstream signaling pathways, such as the MAPK pathway.
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|---|---|
| ln Vitro |
Based on the external GDP/GTP exchange rate, RMC-0331 has an IC50 of 71 nM [1].
In vitro, RMC-0331 is a potent inhibitor of SOS1, disrupting the RAS-SOS1 interaction and blocking RAS activation. Its high potency and selectivity for SOS1 make it a valuable tool for studying RAS signaling. The compound's activity is typically assessed in cell-based assays measuring RAS-GTP levels or downstream signaling, such as ERK phosphorylation. |
| ln Vivo |
RMC-0331 (100-250 mg/kg; vascular; qd; immunocompetent mice) displays single-agent anti-tumor efficacy in a SHP2 mutation model [1].
In vivo, RMC-0331 is an orally bioavailable tool compound used to block RAS activation in animal models. Its ability to disrupt the RAS-SOS1 interaction makes it a valuable tool for studying the role of SOS1 and RAS signaling in cancer and other diseases. Specific in vivo efficacy data, including dosing regimens and animal models, are detailed in the primary literature. |
| Enzyme Assay |
The inhibitory activity of RMC-0331 is assessed using in vitro biochemical assays. The interaction between SOS1 and RAS is measured using techniques such as AlphaScreen, TR-FRET, or surface plasmon resonance (SPR). The compound's ability to disrupt this interaction is quantified, and the IC50 is calculated. Its effect on nucleotide exchange can also be measured using fluorescent GDP-GTP exchange assays.
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| Cell Assay |
The cellular activity of RMC-0331 is evaluated in cancer cell lines with RAS mutations or SOS1 dependency. Cells are treated with varying concentrations of the compound, and its effect on RAS activation is assessed by measuring RAS-GTP levels using pull-down assays. Its effect on downstream signaling, such as ERK phosphorylation, is assessed by Western blot. The compound's effect on cell proliferation is measured using standard assays.
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| Animal Protocol |
In animal studies, RMC-0331 is typically administered orally to mice in models of RAS-driven cancers. Dosing regimens are determined based on its pharmacokinetic properties. Tumor growth inhibition is measured, and at study termination, tumors are harvested for pharmacodynamic analysis, including assessment of RAS-GTP levels and ERK phosphorylation.
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| ADME/Pharmacokinetics |
RMC-0331 is a small molecule with a molecular weight of 499.91 g/mol and a chemical formula of C22H25ClF3N5O3. It is orally bioavailable, indicating favorable properties for in vivo studies. It has a purity of ≥98.70%. Detailed pharmacokinetic parameters, such as half-life and bioavailability, are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Formal toxicology data for RMC-0331 is not extensively documented in the provided sources, as it is a research compound. Its safety profile has not been established in comprehensive toxicology studies. However, its use in preclinical models at efficacious doses suggests it is tolerated in those contexts. Its use is limited to research applications.
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| References | |
| Additional Infomation |
RMC-0331 (RM-023, CAS: 2488788-52-7) is a highly potent and selective SOS1 inhibitor that serves as an in vivo tool compound for studying RAS signaling. Its ability to disrupt the RAS-SOS1 interaction and block RAS activation makes it a valuable tool for investigating the role of SOS1 in cancer and for validating SOS1 as a therapeutic target. It is available from various commercial suppliers for research purposes.
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| Molecular Formula |
C22H25CLF3N5O3
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|---|---|
| Molecular Weight |
499.9138
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| Exact Mass |
499.159
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| Elemental Analysis |
C, 52.86; H, 5.04; Cl, 7.09; F, 11.40; N, 14.01; O, 9.60
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| CAS # |
2488788-52-7
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| Related CAS # |
2488788-52-7
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| PubChem CID |
155687064
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| Appearance |
White to yellow solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
726
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H](C1=CC(=CC(=C1)N)C(F)(F)F)NC2=NC(=NC3=C2CN(C3)C(=O)C4(CCOCC4)OC)Cl
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| InChi Key |
HOBOGRTXXDLZIB-GFCCVEGCSA-N
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| InChi Code |
InChI=1S/C22H25ClF3N5O3/c1-12(13-7-14(22(24,25)26)9-15(27)8-13)28-18-16-10-31(11-17(16)29-20(23)30-18)19(32)21(33-2)3-5-34-6-4-21/h7-9,12H,3-6,10-11,27H2,1-2H3,(H,28,29,30)/t12-/m1/s1
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| Chemical Name |
[4-[[(1R)-1-[3-amino-5-(trifluoromethyl)phenyl]ethyl]amino]-2-chloro-5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl]-(4-methoxyoxan-4-yl)methanone
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| Synonyms |
RMC-0331; RMC0331; RMC 0331; RM-023; RM023; RM 023
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~125 mg/mL (250.1 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (4.16 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.16 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0004 mL | 10.0018 mL | 20.0036 mL | |
| 5 mM | 0.4001 mL | 2.0004 mL | 4.0007 mL | |
| 10 mM | 0.2000 mL | 1.0002 mL | 2.0004 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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