| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
PROTAC KRAS G12C degrader-1 targets the KRAS G12C mutant protein, a key oncogenic driver in several cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer. The compound is a heterobifunctional molecule that binds to KRAS G12C via its KRAS-targeting ligand and to the E3 ubiquitin ligase Cereblon (CRBN) via its CRBN ligand. This induces CRBN/KRASG12C dimerization, leading to ubiquitination and proteasomal degradation of KRAS G12C.
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| ln Vitro |
Compound 10 (PROTAC KRAS G12C degrader-1) binds KRASG12C in vitro and CRBN in cells. It then causes CRBN/KRASG12C dimerization and, in a CRBN-dependent way, degrades GFP-KRASG12C in reporter cells [1].
In vitro, PROTAC KRAS G12C degrader-1 induces CRBN/KRASG12C dimerization and degrades GFP-KRASG12C in reporter cells. It is a KRASG12C PROTAC degrader based on Cereblon. The compound effectively degrades GFP-tagged KRASG12C in reporter cell systems, demonstrating its ability to target and eliminate the oncogenic KRAS G12C protein. Further cellular efficacy data are not reported. |
| ln Vivo |
In vivo, PROTAC KRAS G12C degrader-1 is designed to degrade the KRAS G12C mutant protein in animal models of KRAS G12C-driven cancers. By promoting the degradation of this oncogenic driver, the compound has the potential to inhibit tumor growth and improve outcomes in preclinical models. However, specific in vivo efficacy data have not been published. The compound is based on Cereblon, a commonly used E3 ligase for PROTAC development.
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| Enzyme Assay |
A cell-free binding assay for PROTAC KRAS G12C degrader-1 is not typical for a full PROTAC. To assess CRBN binding, a TR-FRET-based assay can be performed using recombinant His-tagged CRBN and biotin-labeled thalidomide derivative. For KRAS G12C binding, SPR can be used with purified KRAS G12C protein. The compound induces CRBN/KRASG12C dimerization, which can be measured using an AlphaScreen or TR-FRET proximity assay with labeled CRBN and KRAS proteins.
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| Cell Assay |
A GFP-KRASG12C reporter cell line is used for cellular degradation assays. Cells are seeded in 96-well plates. PROTAC KRAS G12C degrader-1 is added at varying concentrations (0.1-1000 nM) and incubated for 6-24 hours. GFP fluorescence is measured as a readout of protein degradation. Alternatively, cells are lysed and analyzed by Western blot using an anti-KRAS antibody. The DC50 (concentration for 50% degradation) is calculated from the dose-response curve.
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| Animal Protocol |
PROTAC KRAS G12C degrader-1 can be studied in mouse xenograft models of KRAS G12C-driven cancers. Female BALB/c nude mice are implanted subcutaneously with KRAS G12C-mutant cancer cells (e.g., NCI-H358 or MIA PaCa-2). When tumors reach 100-150 mm3, mice are randomized and treated intraperitoneally or orally with PROTAC KRAS G12C degrader-1 (10-50 mg/kg) dissolved in a vehicle (10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline). Tumor volume is measured every 2-3 days. KRAS G12C degradation in tumors is confirmed by Western blot.
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| ADME/Pharmacokinetics |
PROTAC KRAS G12C degrader-1 has a molecular weight of 917.47 and the molecular formula C50H54ClFN8O6. The product is a powder with >98% purity. It should be stored at -20degC for up to 3 years. In solvent, it is stable for 6 months at -80degC or 1 month at -20degC. Specific PK parameters have not been reported. The compound is soluble in DMSO. For in vivo use, it requires formulation with a suitable vehicle.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for PROTAC KRAS G12C degrader-1 are available. As a research-grade PROTAC, it is used at low concentrations in vitro and in vivo. The compound is based on Cereblon, which is a well-established E3 ligase for PROTACs with a favorable safety profile. However, formal toxicology studies have not been conducted. Standard safety precautions for handling PROTAC molecules should be followed.
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| References | |
| Additional Infomation |
PROTAC KRAS G12C degrader-1 (CAS: 2984236-79-3) is a research-grade PROTAC and is not approved for clinical use. It is a Cereblon-based KRASG12C PROTAC degrader that induces CRBN/KRASG12C dimerization and degrades GFP-KRASG12C in reporter cells. This compound is a valuable research tool for studying KRAS G12C-driven cancers. This product is for research use only.
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| Molecular Formula |
C50H54CLFN8O6
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|---|---|
| Molecular Weight |
917.47
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| Exact Mass |
916.384
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| CAS # |
2984236-79-3
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| PubChem CID |
162642758
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| Appearance |
Light yellow to green yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
66
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| Complexity |
1700
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C=CC(=O)N1CCN(CC1)C2=NC(=NC3=C(C(=C(C=C32)Cl)C4=CC(=CC5=CC=CC=C54)O)F)NCCCCCCCCCCCCNC6=CC=CC7=C6C(=O)N(C7=O)C8CCC(=O)NC8=O
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| InChi Key |
FMYAMLPDKZOVMB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C50H54ClFN8O6/c1-2-41(63)58-24-26-59(27-25-58)46-36-30-37(51)42(35-29-32(61)28-31-16-11-12-17-33(31)35)44(52)45(36)56-50(57-46)54-23-14-10-8-6-4-3-5-7-9-13-22-53-38-19-15-18-34-43(38)49(66)60(48(34)65)39-20-21-40(62)55-47(39)64/h2,11-12,15-19,28-30,39,53,61H,1,3-10,13-14,20-27H2,(H,54,56,57)(H,55,62,64)
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| Chemical Name |
4-[12-[[6-chloro-8-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-(4-prop-2-enoylpiperazin-1-yl)quinazolin-2-yl]amino]dodecylamino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
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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 :~100 mg/mL (~109.00 mM)
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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 | 1.0900 mL | 5.4498 mL | 10.8995 mL | |
| 5 mM | 0.2180 mL | 1.0900 mL | 2.1799 mL | |
| 10 mM | 0.1090 mL | 0.5450 mL | 1.0900 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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