LC-2
Based on 2 publication(s) in Google Scholar
LC-2 is a potent and first-in-class von Hippel-Lindau-based PROTAC capable of degrading endogenous KRAS G12C, with DC50s between 0.25 and 0.76 μM. LC-2 covalently binds KRAS G12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRAS G12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRAS G12C cell lines.
(Pink: KRas G12C ligand (HY-130149); Blue: VHL ligand (HY-125845); Black: linker).
For research use only. We do not sell to patients.
- Purity: 98.48%
- CAS No.: 2502156-03-6
- Formula: C59H71ClFN11O7S
- Molecular Weight:1132.78
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
Publications Citing Use of MedChemExpress (MCE) LC-2
MoreAll PROTACs Isoforms
More
Biological Activity
|
KRAS(G12C) 0.25-0.76 μM (DC50) |
VHL |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | DC50 |
0.25 μM
Compound: 18; LC-2
|
Protac activity at VHL E3 ligase/KRAS G12 degradation in human MDA-MB-231 cells assessed as VHL degradation by western blot analysis
Protac activity at VHL E3 ligase/KRAS G12 degradation in human MDA-MB-231 cells assessed as VHL degradation by western blot analysis
|
[PMID: 33656892] |
| NCI-H2030 | DC50 |
0.59 μM
Compound: 38
|
Protac activity at VHL/KRAS G12C mutant in human NCI-H2030 cells assessed as degradation of KRAS G12C mutant incubated for 24 hrs by immunoblot assay
Protac activity at VHL/KRAS G12C mutant in human NCI-H2030 cells assessed as degradation of KRAS G12C mutant incubated for 24 hrs by immunoblot assay
|
[PMID: 37542991] |
LC-2 induces degradation of endogenous KRASG12C in multiple KRAS mutant cancer cell (NCI-H2030, MIA PaCa-2, SW1573, NCI-H23 and NCI-H358 cells) with DC50s between 0.25 and 0.76 μM. LC-2-induced KRASG12C degradation occurs via a bona fide PROTAC mechanism. MIA PaCa-2, NCI-H23, and SW1573 cells are treated with 2.5 μM of LC-2 for 6, 24, 48, and 72 h. In all three cell lines, maximal KRAS degradation occurred within 24 h and was sustained up to 72 h[1].
LC-2-induced (2.5 μM; 6-24 hours) KRAS G12C degradation modulates Erk signaling in homozygous and heterozygous KRAS mutant cell lines[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:MIA PaCa-2 cells and NCI-H23 cells
-
Concentration:2.5 μM
-
Incubation Time:6-24 hours
-
Result:Inhibition and degradation of KRAS G12C decreases pErk signaling at 6 and 24 h in homozygous MIA PaCa-2 cells
Chemical Information
-
CAS No. 2502156-03-6
-
Appearance Solid
-
Molecular Weight 1132.78
-
Formula C59H71ClFN11O7S
-
Color Off-white to brown
-
SMILES
O=C(NCC1=CC=C(C=C1)C2=C(N=CS2)C)[C@H]3N(C[C@@H](C3)O)C([C@H](C(C)(C)C)NC(CCOCCCN4[C@@H](CCC4)COC5=NC(N6C[C@@H](N(CC6)C(C(F)=C)=O)CC#N)=C7C(CN(CC7)C8=C9C(Cl)=CC=CC9=CC=C8)=N5)=O)=O
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (2)
-
Journal Impact Factor
-
Most Recent
-
Biochem Biophys Res Commun
Accelerating PROTAC drug discovery: Establishing a relationship between ubiquitination and target protein degradation. [Abstract]2022 Nov 5:628:68-75. PMID: 36084553 -
Solvent & Solubility
DMSO : 100 mg/mL (88.28 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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: ≥ 2.5 mg/mL (2.21 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: 2.08 mg/mL (1.84 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.08 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 (20.8 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.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%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
-
Data Sheet (278 KB)
-
SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
-
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.8828 mL | 4.4139 mL | 8.8278 mL | 22.0696 mL |
| 5 mM | 0.1766 mL | 0.8828 mL | 1.7656 mL | 4.4139 mL | |
| 10 mM | 0.0883 mL | 0.4414 mL | 0.8828 mL | 2.2070 mL | |
| 15 mM | 0.0589 mL | 0.2943 mL | 0.5885 mL | 1.4713 mL | |
| 20 mM | 0.0441 mL | 0.2207 mL | 0.4414 mL | 1.1035 mL | |
| 25 mM | 0.0353 mL | 0.1766 mL | 0.3531 mL | 0.8828 mL | |
| 30 mM | 0.0294 mL | 0.1471 mL | 0.2943 mL | 0.7357 mL | |
| 40 mM | 0.0221 mL | 0.1103 mL | 0.2207 mL | 0.5517 mL | |
| 50 mM | 0.0177 mL | 0.0883 mL | 0.1766 mL | 0.4414 mL | |
| 60 mM | 0.0147 mL | 0.0736 mL | 0.1471 mL | 0.3678 mL | |
| 80 mM | 0.0110 mL | 0.0552 mL | 0.1103 mL | 0.2759 mL |
LC-2 Related Classifications
HY-137516 Related Classifications
Powered by Bioz