L013
L013 is an orally active and selective NRF2 PROTAC degrader. L013 directly binds to the NRF2 protein and promotes NRF2 ubiquitination and UPS-related degradation through a Cullin-dependent, CRBN-related process. L013 inhibits RNA polymerase II transcriptional elongation and downregulates NFE2L2 transcript levels. L013 selectively reduces NRF2 protein/mRNA and inhibits proliferation/colony formation in esophageal squamous cell carcinoma cells with NRF2 hyperactivation. L013 inhibits tumor growth in the KYSE150 esophageal squamous cell carcinoma xenograft mouse model and reduces intratumoral NRF2 and Ki-67 protein levels. L013 can be used for research on esophageal squamous cell carcinoma and lung squamous cell carcinoma.
(Pink: Keap1-Nrf2 ligand (HY-189822); Blue: Ligands for E3 Ligase ligand (HY-41547); Black: linker (HY-W574507)).
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 分子式: C42H53ClN12O4
- 分子量:825.40
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
IC50 & Target
[1]|
RNA Polymerase |
体外実験
L013 decreases NFE2L2 mRNA and reduces pSer2 CTD occupancy/RNA Pol II CTD Ser2 phosphorylation in KYSE150 ESCC cells, consistent with impaired transcriptional elongation[1].
L013 (500 nM-1 μM; 1-24 h) promotes NRF2 ubiquitination and enhances NRF2-CRBN binding in KYSE150 and KYSE510 ESCC cells, whereas UPS/proteasome inhibition only partially reverses L013-mediated NRF2 reduction[1].
L013 (10 nM-1 μM; 48-72 h) inhibits organoid viability and degrades NRF2 in ESCC and LUSC organoids, with selective sensitivity in ESCC#3 and LUSC#1 with high NRF2 expression[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KYSE150 and KYSE510 ESCC cells
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Concentration:1 nM, 10 nM, 50 nM, 100 nM, 200 nM, 500 nM, 1 μM, 5 μM, 10 μM (dose-depend)
1 μM (time-depend) -
Incubation Time:8 h (dose-depend)
0, 1, 2, 4, 6, 8 h (time-depend) -
Result:Was a rapid and selective NRF2 degrader in KYSE150 and KYSE510 ESCC cells.
Parmacokinetics
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (male, 6-week-old, 1.5×106 KYSE150 cells)[1]
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Dosage:10 mg/kg
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Administration:oral gavage; every other day
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Result:Inhibited tumor growth in KYSE150 xenografts, with reduced tumor volume and tumor weight compared with vehicle control groups.
IHC showed reduced NRF2 and Ki-67 levels in L013-treated xenografts.
- RNA extraction experimental
- Ki-67 Immunostaining Proliferation Assay
- Patient-Derived Xenograft (PDX)
- Patient-Derived Orthotopic Xenograft (PDOX)
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Soft Agar Colony Formation Assay
- Colony Formation (Clonogenic) Assay
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Cell Viability Determination by MTT Colorimetric Assay
- Intraperitoneal/Peritoneal Dissemination Xenograft
- How to Choose the Right Model Animal
化学情報
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分子量 825.40
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分子式 C42H53ClN12O4
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SMILES
CN(N=C1)C(CC2CC2)=C1C3=NC(N[C@H](CC4)CC[C@@H]4NCC5=CN(N=N5)CCCCCCCCNC6=CC=CC(C(N7C8CCC(NC8=O)=O)=O)=C6C7=O)=NC=C3Cl
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
L013 関連分類
HY-210438 関連分類
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