| Targets |
DC50: 98.4 nM (SOS1)[1]
PROTAC SOS1 degrader-1 TFA targets SOS1 (Son of Sevenless homolog 1), a guanine nucleotide exchange factor (GEF) that activates RAS proteins by promoting the exchange of GDP for GTP. SOS1 is a key upstream activator of KRAS, and its inhibition or degradation can suppress KRAS signaling. The compound operates through a unique mechanism: it binds to SOS1 and recruits an E3 ubiquitin ligase via its linker, leading to ubiquitination and subsequent proteasomal degradation of SOS1. |
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| ln Vitro |
In vitro, PROTAC SOS1 degrader-1 TFA potently degrades SOS1 with a DC50 of 98.4 nM. It shows antiproliferative activity in cancer cells with various KRAS mutations. The degradation of SOS1 disrupts the RAS signaling pathway, inhibiting cell proliferation and inducing apoptosis in KRAS-driven cancer cells. The compound's activity is mediated through the formation of a ternary complex between the PROTAC molecule, SOS1, and the E3 ubiquitin ligase.
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| ln Vivo |
In vivo, PROTAC SOS1 degrader-1 TFA has demonstrated antitumor efficacy in preclinical models. By degrading SOS1 and suppressing KRAS signaling, the compound inhibits tumor growth in KRAS-mutant cancers. The compound shows low toxicity, making it a promising candidate for targeted cancer therapy research. Detailed in vivo efficacy data, including effects on tumor growth and survival in xenograft models, are described in the primary literature.
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| Enzyme Assay |
Non-cellular binding assays for PROTAC SOS1 degrader-1 TFA involve studying its interactions with SOS1 and E3 ubiquitin ligase components. Binding affinity to SOS1 can be measured using techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The formation of the ternary complex (PROTAC-SOS1-E3 ligase) can be assessed using biochemical assays such as AlphaScreen or pull-down experiments. These assays confirm the compound's mechanism of action.
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| Cell Assay |
In vitro cellular experiments with PROTAC SOS1 degrader-1 TFA are conducted in cancer cell lines with various KRAS mutations. Cells are treated with the compound at various concentrations, and SOS1 protein levels are assessed by Western blotting to confirm degradation and determine the DC50. Cell viability and proliferation are evaluated using standard assays such as CellTiter-Glo or MTT. Downstream signaling pathway effects (e.g., ERK phosphorylation) are assessed to confirm pathway inhibition.
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| Animal Protocol |
In vivo animal studies for PROTAC SOS1 degrader-1 TFA are performed in murine xenograft models using KRAS-mutant cancer cell lines. Tumor-bearing mice are treated with the compound via appropriate routes of administration. Tumor growth is monitored over time, and endpoints include tumor volume measurements, survival analysis, and pharmacodynamic assessments of SOS1 degradation and KRAS pathway inhibition in tumor tissues. Efficacy and toxicity are evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PROTAC SOS1 degrader-1 TFA are characterized during preclinical development. As a PROTAC molecule, it has a larger molecular weight and different physicochemical properties compared to traditional small molecule inhibitors. The TFA salt form enhances solubility. Detailed pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution would be determined in appropriate animal models. Storage conditions should follow the supplier's recommendations.
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| Toxicity/Toxicokinetics |
Toxicity data for PROTAC SOS1 degrader-1 TFA are generated during preclinical development. The compound has demonstrated low toxicity in preclinical studies. As a protein degrader, potential toxicities may include off-target degradation effects. Comprehensive toxicology studies would assess safety margins and identify target organ toxicities. Researchers should consult the safety data sheet and handle the compound with appropriate laboratory safety precautions for research use only.
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| References | |
| Additional Infomation |
PROTAC SOS1 degrader-1 TFA is a research compound that operates through a unique mechanism involving the formation of a ternary complex between the PROTAC molecule, SOS1, and the E3 ubiquitin ligase. The compound shows antiproliferative activity in cancer cells with various KRAS mutations. It is a promising candidate for targeted cancer therapy research. All products are for research use only.
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| Molecular Formula |
C59H77CLF4N10O6S
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|---|---|
| Molecular Weight |
1165.82
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| Appearance |
White to off-white 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~85.78 mM; with sonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8578 mL | 4.2888 mL | 8.5777 mL | |
| 5 mM | 0.1716 mL | 0.8578 mL | 1.7155 mL | |
| 10 mM | 0.0858 mL | 0.4289 mL | 0.8578 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.
Products are for research use only; We do not sell to patients
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