RSC-1255
Based on 1 Customer Validation
RSC-1255 is a potent and selective Vacuolar H⁺-ATPase (V-ATPase) inhibitor that directly binds the mammalian V-ATPase complex with a Kd = 23 nM. RSC-1255 exhibits preferential cytotoxicity toward KRAS-mutant cancer cells, especially KRASG13D and KRASG12V cells. RSC-1255 induces apoptosis and blocks lysosomal acidification, autophagy, and macropinocytosis in cancer cells. RSC-1255 can be used for the study of KRAS-driven lung and colon cancers.
For research use only. We do not sell to patients.
- Purity : 99.91%
- CAS No.: 2171015-78-2
- Formula: C27H25ClF4N4O3
- Molecular Weight:564.96
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
KRAS G13D |
KRas G12V |
In Vitro
RSC-1255 (249C) (1 μM; 1 h) inhibits V-ATPase–mediated proton pumping and lysosomal acidification in HEK293T cells[1].
RSC-1255 (1 μM; 1 h) disrupts V-ATPase assembly by increasing membrane-associated V1 subunits in HEK293T cells[1].
RSC-1255 exhibits potent growth-inhibitory activity in human cancer cell lines, with IC50 values of 0.073 μM in A549 (KRAS-mutant), 0.06 μM in LOX IMVI (BRAFV600E), and 0.022μM in MelJuso (HRASG13D/NRASQ61L) cells[1].
RSC-1255 (0-10 μM; 72 h) selectively reduces cell viability in KRAS-mutant mouse embryonic fibroblasts (MEFs) with the highest sensitivity in KRASG13D and KRASG12V cells[1].
RSC-1255 (1 μM; 2-24 h) blocks autophagic flux, increasing SQSTM1/p62 and LC3-II accumulation in A549 cells[1].
RSC-1255 (1 μM; 1 h) increases lysosomal pH in KRASG13D MEFs, reversing their highly acidic basal lysosomal state[1].
RSC-1255 (1 μM; 1 h) inhibits V-ATPase–dependent proton transport in FITC-loaded lysosomes, showing the strongest inhibition in KRASG13D MEFs[1].
RSC-1255 (1 μM; 24 h) enlarges autophagic vesicles and blocks lysosome-autophagosome fusion in KRASG13D, KRASG12V and BRAFV600E MEFs[1].
RSC-1255 (1 μM; 2 h) markedly reduces macropinocytosis levels in MEFs, with KRASG13D cells showing the strongest suppression[1].
RSC-1255 ((1 μM; 24 h) induces apoptosis in KRAS-mutant MEFs, with KRASG13D, KRASG12V and BRAFV600E cells showing the highest Annexin V⁺/PI⁺levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK293T cells
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Concentration:1 μM
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Incubation Time:1h
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Result:Increased membrane-associated V1 subunit B2 was observed, indicating altered V-ATPase assembly after treatment.
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Cell Line:A549 cells
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Concentration:1 μM
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Incubation Time:2 , 4 , 8 , 20 , 24 h
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Result:Time-dependent accumulation of SQSTM1/p62 and LC3-II, indicating autophagic flux inhibition.
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Cell Line:MEF KRAS mutants (KRASG13D, KRASG12V, KRASG12D, KRASG12S, KRASG12C, KRASQ61L, KRASQ61R, WT)
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Concentration:0-10 μM
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Incubation Time:72 h
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Result:Highest sensitivity in KRASG13D and KRASG12V MEFs with the lowest IC50 values; minimal sensitivity in WT MEFs.
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Cell Line:MEFs expressing KRASG13D, KRASG12V, BRAFV600E and other KRAS mutants
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Concentration:1 μM
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Incubation Time:24h
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Result:Increased of Annexin V+/PI+ apoptotic cells, with KRASG13D,KRASG12V and BRAFV600E MEFs showing the strongest apoptotic responses.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:A549 (KRASG12S) lung cancer xenografts were established in five-week-old athymic mice.
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Dosage:10 mg/kg
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Administration:Intraperitoneal injection (i.p.); twice daily
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Result:Significantly reduced tumor volumes in A549 xenograft-bearing mice during the treatment period.
Increased LC3-I/II levels in tumor tissues, indicating autophagy inhibition in vivo.
No significant systemic toxicity, with normal body weight, organ weights and hematological parameters.
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Animal Model:SW48 xenograft models bearing parental or KRAS-mutant SW48 cells (KRASG12D/+, KRASG12V/+, KRASG13D/+) were established in five-six-week-old athymic mice].
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Dosage:10 mg/kg
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Administration:Intraperitoneal injection (i.p.); 2 weeks.
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Result:Significant tumor growth inhibition in KRAS-mutant SW48 xenografts, with the strongest effects in KRASG13D/+ and KRASG12V+ tumors.
Minimal response in parental SW48 tumors, consistent with lower in vitro sensitivity.
No significant changes in body weight or systemic toxicity during treatment.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Cell Cytotoxicity Assay
- Mammalian live/dead viability and cytotoxicity staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- Autophagy
- Apoptosis Solutions
- Lysosome and acidic-vesicle live-cell staining
- Macroautophagy Solutions
- Cell Viability Determination by MTT Colorimetric Assay
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2171015-78-2
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Appearance Solid
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Molecular Weight 564.96
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Formula C27H25ClF4N4O3
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Color Off-white to light yellow
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SMILES
O=C(C1(C)N(C2=CC=C(C=C2F)F)N=C(C1C3=CC=C(Cl)O3)C4=C(F)C=C(F)C=C4)NCC5OCCN(C5)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (88.50 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. 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. 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)
In Vivo:
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: ≥ 1.25 mg/mL (2.21 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 1.25 mg/mL (2.21 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 1.25 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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.
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.
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.
Purity & Documentation
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Data Sheet (286 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
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. 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 |
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| DMSO | 1 mM | 1.7700 mL | 8.8502 mL | 17.7004 mL | 44.2509 mL |
| 5 mM | 0.3540 mL | 1.7700 mL | 3.5401 mL | 8.8502 mL | |
| 10 mM | 0.1770 mL | 0.8850 mL | 1.7700 mL | 4.4251 mL | |
| 15 mM | 0.1180 mL | 0.5900 mL | 1.1800 mL | 2.9501 mL | |
| 20 mM | 0.0885 mL | 0.4425 mL | 0.8850 mL | 2.2125 mL | |
| 25 mM | 0.0708 mL | 0.3540 mL | 0.7080 mL | 1.7700 mL | |
| 30 mM | 0.0590 mL | 0.2950 mL | 0.5900 mL | 1.4750 mL | |
| 40 mM | 0.0443 mL | 0.2213 mL | 0.4425 mL | 1.1063 mL | |
| 50 mM | 0.0354 mL | 0.1770 mL | 0.3540 mL | 0.8850 mL | |
| 60 mM | 0.0295 mL | 0.1475 mL | 0.2950 mL | 0.7375 mL | |
| 80 mM | 0.0221 mL | 0.1106 mL | 0.2213 mL | 0.5531 mL |
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