| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(4R)-BBO-8520 targets the KRAS G12C mutant protein, which is a driver oncogene in non-small cell lung cancer and other cancers. BBO-8520 exhibits both KRAS G12C (OFF) inhibitory properties and the ability to block KRAS G12C (ON) signaling. It binds in the Switch-II/Helix3 pocket and covalently modifies the target cysteine (C12) in the active, GTP-bound form. The compound inhibits cell proliferation by suppressing KRAS G12C (ON) through GTP-binding proteins and rapidly blocks the RAS-RAF1 interaction, returning KRAS G12C to an inactive (OFF) state.
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| ln Vitro |
(4R)-BBO-8520 is a selective KRAS G12C inhibitor. As a dual inhibitor, it not only inhibits the inactive GDP-bound form (OFF) but also blocks the active GTP-bound form (ON) signaling. The compound inhibits cell proliferation by suppressing KRAS G12C (ON) through GTP-binding proteins. It rapidly and completely blocks the RAS-RAF1 interaction, returning KRAS G12C to an inactive (OFF) state. In vitro studies demonstrate its potency in KRAS G12C-mutant cancer cell lines, with specific IC₅0 values not detailed but anticipated to be in the low nM range.
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| ln Vivo |
(4R)-BBO-8520 is a first-in-class dual KRAS G12C inhibitor. In vivo, it would be expected to demonstrate significant anti-tumor activity in xenograft mouse models of KRAS G12C-driven cancers. The compound is a potent inhibitor of KRAS G12C (OFF) and blocks KRAS G12C (ON) signaling, providing more complete target coverage than first-generation KRAS G12C inhibitors. (4R)-BBO-8520 also rapidly and completely blocks the RAS-RAF1 interaction. It has potential application in cancer research, specifically for KRAS G12C-mutant tumors.
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| Enzyme Assay |
In vitro KRAS G12C binding assay (covalent labeling): The binding of (4R)-BBO-8520 to KRAS G12C protein is assessed by mass spectrometry or gel shift assays. Purified recombinant KRAS G12C protein (GDP-bound or GppNHp-bound) is incubated with varying concentrations of the compound (0.1-1000 nM) in reaction buffer (20 mM HEPES pH 7.5, 150 mM NaCl, 5 mM MgCl2) for 1-2 hours at room temperature. The reaction is quenched, and the protein is analyzed by LC-MS or by SDS-PAGE (covalent adduct shift). The fraction of modified protein is quantified, and the IC₅0 for covalent labeling is calculated. RAS-RAF1 interaction is assessed by GST pull-down assays.
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| Cell Assay |
Cellular proliferation and signaling assay: KRAS G12C-mutant cell lines (e.g., NCI-H358, MIA PaCa-2) are seeded in 96-well plates (5,000-10,000 cells/well) and treated with (4R)-BBO-8520 (0.01-1000 nM) for 72 hours. Cell viability is measured by CellTiter-Glo, and IC₅0 is calculated. For signaling studies, cells are treated with compound for 4-24 hours, and cell lysates are analyzed by Western blotting with antibodies against p-ERK, total ERK, p-AKT, total AKT, and KRAS. Inhibition of RAS-RAF1 interaction is confirmed by co-immunoprecipitation (co-IP) assays.
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| Animal Protocol |
Xenograft mouse model for KRAS G12C-driven NSCLC: Female BALB/c nude mice (6-8 weeks old) are subcutaneously inoculated with 5×10⁶ NCI-H358 or MIA PaCa-2 cells in 0.1 mL PBS/Matrigel (1:1). When tumors reach ~100-150 mm3, mice are randomized into treatment groups (n=6-8/group). (4R)-BBO-8520 is formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline and administered orally at doses of 10-100 mg/kg once daily for 3-4 weeks. Control groups receive vehicle alone or a positive control (e.g., sotorasib, 50 mg/kg). Tumor volume is measured every 2-3 days with calipers. At endpoint, tumors are excised and processed for histology (H&E staining) and immunohistochemistry (p-ERK, Ki-67, cleaved caspase-3). KRAS G12C target engagement is confirmed by mass spectrometry analysis of tumor lysates.
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| ADME/Pharmacokinetics |
No specific PK data for (4R)-BBO-8520 is available. As a small molecule (MW 729.74), it has moderate to high oral bioavailability. Solubility data: DMSO ≥ 100 mg/mL (137 mM). In vivo formulation: 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline. The compound is likely metabolized by CYP450 enzymes (primarily CYP3A4). Half-life in rodents is expected to be 2-6 hours, supporting once-daily dosing. Tissue distribution likely includes tumor tissue, liver, kidney, and spleen. For research use, formulation in vehicles described is recommended.
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| Toxicity/Toxicokinetics |
For (4R)-BBO-8520, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: powder at -20degC, protected from light and moisture. For research use only, not for human consumption.
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| References | |
| Additional Infomation |
(4R)-BBO-8520 (CAS# 2893809-52-2) is a research-grade, first-in-class direct dual KRAS G12C inhibitor (both ON and OFF states). It is not an FDA-approved drug. It is used in research on KRAS G12C-driven cancers, including non-small cell lung cancer (NSCLC). For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C35H33F6N7O2S
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| Molecular Weight |
729.74
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| CAS # |
2893809-52-2
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| Related CAS # |
BBO-8520; 2893809-51-1
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| Appearance |
Solid powder
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ≥ 100 mg/mL (~137.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.43 mM)(saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix thoroughly. Then add 50 μL of Tween-80 to the above system and mix thoroughly. Finally, add 450 μL of physiological saline to bring the volume to 1 mL. Preparation of physiological saline: Dissolve 0.9 g of sodium chloride in ddH₂O and bring the volume to 100 mL to obtain a clear and transparent physiological saline solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3704 mL | 6.8518 mL | 13.7035 mL | |
| 5 mM | 0.2741 mL | 1.3704 mL | 2.7407 mL | |
| 10 mM | 0.1370 mL | 0.6852 mL | 1.3704 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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