Lw13
Lw13 is a Hsp90 PROTAC degrader. Lw13 induces Hsp90 degradation via the ubiquitin-proteasome system, destabilizes client proteins HER2 and AKT, and blocks the activation of the HER2/AKT/mTOR signaling pathway. Lw13 inhibits the metastasis of cervical cancer cells, induces cell cycle arrest and apoptosis (apoptosis). Lw13 exerts synergistic anti-tumor activity with Cisplatin (HY-17394). Lw13 is applicable to cervical cancer-related research.
(Pink: HSP90 ligand (HY-10213); Blue: Cereblon ligand (HY-A0003); Black: linker (HY-W129147)).
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: C46H55F3N8O8
- 分子量:904.97
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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
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| C-33-A | IC50 |
0.07 μM
Compound: lw13
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Antiproliferative activity against human C-33-A cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human C-33-A cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay
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[PMID: 38861809] |
| HeLa | IC50 |
0.08 μM
Compound: lw13
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Antiproliferative activity against human HeLa cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human HeLa cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay
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[PMID: 38861809] |
| SiHa | IC50 |
0.05 μM
Compound: lw13
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Antiproliferative activity against human SiHa cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human SiHa cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay
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[PMID: 38861809] |
体外実験
Lw13 (72 h) potently inhibits the proliferation of SiHa, HeLa, C33A and CaSki cervical cancer cells, with IC50 values of 0.05, 0.08, 0.07 and 0.05 μM, respectively[1].
Lw13 (0.01-1 μM; 4-48 h) degrades Hsp90 in a time- and dose-dependent manner in SiHa cervical cancer cells, with the degradation effect peaking at a concentration of 0.05 μM after 10 h of incubation[1].
Lw13 (0.01-1 μM; 14 days) inhibits colony formation of SiHa cervical cancer cells in a concentration-dependent manner[1].
Lw13 (0.01-1 μM; 24-48 h) inhibits the migration of SiHa cervical cancer cells[1].
Lw13 (0.05-10 μM) acts synergistically with cisplatin to inhibit the proliferation of SiHa cervical cancer cells[1].
Lw13 (0.01-1 μM) inhibits the activation of the HER2/AKT/mTOR signaling pathway in SiHa cervical cancer cells by reducing the protein levels of HER2 and AKT, as well as decreasing the phosphorylation of AKT and mTOR[1].
Lw13 (0.05-10 μM; 48 h) induces concentration-dependent apoptosis in SiHa cervical cancer cells, with significant increases in both early and late apoptotic cell populations after 48 h of incubation[1].
Lw13 (0.05-10 μM; 48 h) induces concentration-dependent G2/M cell cycle arrest in SiHa cervical cancer cells after 48 h of incubation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SiHa cervical cancer cells
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Concentration:0.01, 0.025, 0.05, 0.075, 0.1, 0.5 and 1 μM
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Incubation Time:4, 6, 8, 10, 12, 24, 36 and 48 h
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Result:Reduced Hsp90 levels by 8 h, with maximum degradation at 10 h, and levels returned to DMSO control levels by 36 h when treated with 1 μM.
Achieved maximum Hsp90 degradation at 0.05 μM (10 h incubation), with a hook effect observed at concentrations above 0.075 μM.
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Cell Line:CaSki cervical cancer cells
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Concentration:0.005-5 μM
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Incubation Time:10 h
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Result:Significantly reduced Hsp90 protein levels when treated with 0.05 μM for 10 h.
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Cell Line:SiHa cervical cancer cells
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Concentration:0.01, 0.05, 0.1, 0.5 and 1 μM
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Incubation Time:14 days
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Result:Inhibited cell colony formation in a concentration-dependent manner, with effective inhibition at concentrations ≥ 0.05 μM, and was more effective than cisplatin at blocking colony formation.
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Cell Line:SiHa cervical cancer cells
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Concentration:0.01, 0.05, 0.1, 0.5 and 1 μM
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Incubation Time:24 and 48 h
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Result:Inhibited cell migration at 0.05 μM.
Almost completely blocked cell migration within 48 h when treated with 0.5 μM.
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Cell Line:SiHa cervical cancer cells
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Concentration:0.05, 1, 2.5, 5 and 10 μM
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Incubation Time:48 h
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Result:Induced cell apoptosis in a concentration-dependent manner, with a strong correlation to late-stage apoptosis.
Increased early-stage apoptosis compared to untreated cells.
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Cell Line:SiHa cervical cancer cells
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Concentration:0.05, 1, 2.5, 5 and 10 μM
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Incubation Time:48 h
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Result:Increased the proportion of cells arrested in the G2/M phase in a concentration-dependent manner, with the highest arrest observed at 10 μM (30% of cells in G2/M phase).
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 (female, 4 weeks old, subcutaneous cervical cancer xenograft model via injection of 5×106 SiHa cells into right lower axilla, treatment initiated when tumor volume reached 100 mm3)[1]
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Dosage:2 mg/kg
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Administration:i.p.; every two days for 30 days
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Result:Exhibited higher tumor growth inhibition (TGI) than cisplatin at the same dose.
Enhanced cisplatin's antitumor activity with a higher TGI index than either agent alone when combined with 2 mg/kg cisplatin.
Caused no significant body weight loss, indicating no overt toxicity.
Reduced Ki67 staining in tumor tissues compared to the control group, indicating decreased tumor cell proliferation.
化学情報
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分子量 904.97
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分子式 C46H55F3N8O8
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SMILES
O=C(N)C1=C(N[C@@H]2CC[C@@H](OC(CNC(CCCCCCCNC3=C4C(C(N(C5CCC(NC5=O)=O)C4)=O)=CC=C3)=O)=O)CC2)C=C(N6N=C(C(F)(F)F)C7=C6CC(C)(C)CC7=O)C=C1
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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)
Lw13 関連分類
HY-162589 関連分類
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