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)).
For research use only. We do not sell to patients.
- Formula: C46H55F3N8O8
- Molecular Weight:904.97
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Storage:
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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
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] |
In Vitro
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].
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).
In Vivo
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.
Chemical Information
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Molecular Weight 904.97
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (110.50 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
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: ≥ 5 mg/mL (5.53 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 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.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%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
References
Complete Stock Solution Preparation Table
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1050 mL | 5.5250 mL | 11.0501 mL | 27.6252 mL |
| 5 mM | 0.2210 mL | 1.1050 mL | 2.2100 mL | 5.5250 mL | |
| 10 mM | 0.1105 mL | 0.5525 mL | 1.1050 mL | 2.7625 mL | |
| 15 mM | 0.0737 mL | 0.3683 mL | 0.7367 mL | 1.8417 mL | |
| 20 mM | 0.0553 mL | 0.2763 mL | 0.5525 mL | 1.3813 mL | |
| 25 mM | 0.0442 mL | 0.2210 mL | 0.4420 mL | 1.1050 mL | |
| 30 mM | 0.0368 mL | 0.1842 mL | 0.3683 mL | 0.9208 mL | |
| 40 mM | 0.0276 mL | 0.1381 mL | 0.2763 mL | 0.6906 mL | |
| 50 mM | 0.0221 mL | 0.1105 mL | 0.2210 mL | 0.5525 mL | |
| 60 mM | 0.0184 mL | 0.0921 mL | 0.1842 mL | 0.4604 mL | |
| 80 mM | 0.0138 mL | 0.0691 mL | 0.1381 mL | 0.3453 mL | |
| 100 mM | 0.0111 mL | 0.0553 mL | 0.1105 mL | 0.2763 mL |
Lw13 Related Classifications
HY-162589 Related Classifications
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