| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
K-Ras (mutant KRAS G12C) for targeted degradation; Cereblon E3 ubiquitin ligase for recruitment via the Cereblon-binding ligand. The PROTAC binds to mutant K-Ras and recruits Cereblon, leading to ubiquitination and proteasomal degradation of the K-Ras protein.
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|---|---|
| ln Vitro |
Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. Target proteins are broken down by PROTAC through the intracellular ubiquitin-proteasome system coupling [1].
In vitro, this PROTAC effectively degrades K-Ras in SW1573 cells, with ≥70% degradation efficacy. The compound's chemical properties: molecular weight 999.12, formula C53H62N10O10. Solubility: 33.33 mg/mL in DMSO (33.36 mM). Purity: ≥98%. When PROTAC K-Ras Degrader-1 binds to mutant KRAS G12C, it recruits E3 ubiquitin ligase to the mutant protein, leading to its degradation. The compound is a potent degrader based on PROTAC technology. |
| ln Vivo |
In vivo, this PROTAC is expected to have antitumor activity by degrading K-Ras in tumors. It serves as a tool to validate K-Ras degradation as a therapeutic strategy for KRAS-mutant cancers. Specific in vivo efficacy data (e.g., xenograft studies) are not extensively reported in publicly available sources, but the compound is designed for research applications in targeted protein degradation.
|
| Enzyme Assay |
Cellular degradation assay: SW1573 cells (KRAS G12C mutant) are seeded in 6-well plates and treated with PROTAC K-Ras Degrader-1 (0.01-1 uM) for 24 hours. Cells are lysed in RIPA buffer, and 30-40 ug protein is resolved by SDS-PAGE. Proteins are transferred to PVDF membranes and probed with anti-K-Ras (or anti-pan-Ras) and anti-GAPDH antibodies. Band intensity is quantified by densitometry to determine degradation percentage (Dmax) and DC50. ≥70% degradation efficacy is reported.
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| Cell Assay |
Cell proliferation assay: SW1573 or other KRAS G12C mutant cancer cell lines are seeded in 96-well plates and treated with PROTAC K-Ras Degrader-1 (0.001-10 uM) for 48-72 hours. Cell viability is measured using MTT, CellTiter-Glo, or CCK-8 assays. IC50 values for growth inhibition are determined from dose-response curves.
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| Animal Protocol |
Mouse xenograft models: The PROTAC could be tested in tumor-bearing mice (e.g., SW1573 xenografts in immunodeficient mice) with administration via intraperitoneal injection (10-50 mg/kg, daily or every other day) for 14-21 days. Tumor volumes are measured, and tumors are harvested for K-Ras protein level analysis by Western blot and immunohistochemistry to confirm target degradation in vivo.
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| ADME/Pharmacokinetics |
As a PROTAC (MW 999.12), its pharmacokinetics are influenced by its large size and properties. It may have limited oral bioavailability and require parenteral administration. PK parameters such as half-life, clearance, and bioavailability are not extensively reported. Storage: dry, dark, -20degC for up to 1 year.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported. As a targeted degrader, it may have off-target effects on other proteins. The Cereblon-based recruitment may also lead to degradation of other Cereblon neosubstrates (e.g., IKZF1/3), which could have immunological effects.
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| References | |
| Additional Infomation |
This is a research compound, not an approved drug. It is a tool for studying K-Ras degradation and exploring PROTAC technology for targeting the traditionally "undruggable" K-Ras oncogene. CAS number: 2378258-52-5. For research use only, not for human use.
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| Molecular Formula |
C53H62N10O10
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|---|---|
| Molecular Weight |
999.12039232254
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| Exact Mass |
998.465
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| CAS # |
2378258-52-5
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| PubChem CID |
139579413
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
22
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| Heavy Atom Count |
73
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| Complexity |
1970
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
O(CCOCCOCCOCCNC1=CC=CC2C(N(C(C=21)=O)C1C(NC(CC1)=O)=O)=O)[C@H]1CN(C)[C@H](COC2=NC3CN(C4=CC=CC5C=CC=CC4=5)CCC=3C(=N2)N2CCN(C(C=C)=O)[C@@H](CC#N)C2)C1
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| InChi Key |
KGFCORDWMRCVAC-VYIZRSQBSA-N
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| InChi Code |
InChI=1S/C53H62N10O10/c1-3-47(65)62-22-21-61(31-36(62)16-18-54)49-40-17-20-60(44-13-6-9-35-8-4-5-10-39(35)44)33-43(40)56-53(58-49)73-34-37-30-38(32-59(37)2)72-29-28-71-27-26-70-25-24-69-23-19-55-42-12-7-11-41-48(42)52(68)63(51(41)67)45-14-15-46(64)57-50(45)66/h3-13,36-38,45,55H,1,14-17,19-34H2,2H3,(H,57,64,66)/t36-,37-,38+,45?/m0/s1
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| Chemical Name |
2-[(2S)-4-[2-[[(2S,4R)-4-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]-1-methylpyrrolidin-2-yl]methoxy]-7-naphthalen-1-yl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-prop-2-enoylpiperazin-2-yl]acetonitrile
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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. |
| 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 : ~33.33 mg/mL (~33.36 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.50 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 25.0 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: ≥ 2.5 mg/mL (2.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0009 mL | 5.0044 mL | 10.0088 mL | |
| 5 mM | 0.2002 mL | 1.0009 mL | 2.0018 mL | |
| 10 mM | 0.1001 mL | 0.5004 mL | 1.0009 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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