HDAC degrader-2
Based on 1 Customer Validation
HDAC degrader-2 is a HDAC degrader, and its DC50 for HDAC1 in MM.1S cells is 2.55 μM. HDAC degrader-2 recruits and covalently binds to DDB1, thereby inducing proteasomal degradation of HDAC1 and HDAC2. HDAC degrader-2 inhibits HDAC6 activity and increases the acetylation levels of α-tubulin and histone H3. HDAC degrader-2 induces early and late apoptosis and reduces the proliferative capacity of cancer cells. HDAC degrader-2 can be used for research on multiple myeloma and breast cancer.
For research use only. We do not sell to patients.
- Purity : 98.88%
- Formula: C32H35ClN4O5
- Molecular Weight:591.10
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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 |
|---|---|---|---|---|
| MM.1S | IC50 |
3.28 μM
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Antiproliferative activity against human MM.1S multiple myeloma cells assessed via CellTiterGlo 2.0 cell viability assay.
Antiproliferative activity against human MM.1S multiple myeloma cells assessed via CellTiterGlo 2.0 cell viability assay.
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41089485 |
| MCF7 | IC50 |
3.46 μM
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Antiproliferative activity against human MCF-7 breast cancer cells assessed via MTT cell viability assay.
Antiproliferative activity against human MCF-7 breast cancer cells assessed via MTT cell viability assay.
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41089485 |
In Vitro
HDAC degrader-2 (SZ-2) (1-10 μM; 24 h) potently degrades HDAC1 and HDAC2 (with Dmax, 24 h values of 99% and 90%, respectively) in MM.1S cells after 24-hour treatment, with minimal effect on other HDAC subtypes at concentrations ≤5 μM[1].
HDAC degrader-2 (10 μM; 24 h) degrades HDAC1 (with a Dmax, 24 h value of 38%) in MCF-7 cells after 24-hour treatment at 10 μM, with no effect on HDAC6[1].
HDAC degrader-2 (0.016-10 μM; 24 h) induces concentration-dependent degradation of HDAC1 in MM.1S cells after 24-hour treatment, with a DC50, 24 h value of 2.55 μM[1].
HDAC degrader-2 inhibits purified HDAC1 with an IC50 of 6.41 μM and purified HDAC6 with an IC50 of 0.479 μM, exhibiting preferential potency against HDAC6[1].
HDAC degrader-2 (5 μM; 24 h) inhibits HDAC6 and class I HDACs in MM.1S cells after 24-hour treatment at 5 μM, as shown by increased levels of acetylated α-tubulin and acetylated histone H3[1].
HDAC degrader-2 (10 μM; 24 h) induces HDAC1 degradation in MM.1S cells after 24-hour treatment at 10 μM in a DDB1-dependent manner, as confirmed by lack of activity with the non-DDB1-binding analog SZ-2-N[1].
HDAC degrader-2 potently inhibits proliferation of MM.1S cells with an IC50 of 3.28 μM and MCF-7 cells with an IC50 of 3.46 μM[1].
HDAC degrader-2 (SZ-2) (5 μM; 48 h) induces significant apoptosis in MM.1S cells after 48-hour treatment at 5 μM, with activity comparable to the control agent Ricolinostat (HY-16026)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MM.1S multiple myeloma cells
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Concentration:1 μM; 5 μM; 10 μM
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Incubation Time:24 h
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Result:Induced significant degradation of HDAC1 and HDAC2 in MM.1S cells.
Caused no degradation of HDAC3, HDAC4, HDAC6, or HDAC8 at 5 μM, though a slight reduction in these proteins was seen at 10 μM.
Reached maximum degradation (D_max, 24 h) of HDAC1 at 99%, and HDAC2 at 90%.
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Cell Line:MM.1S multiple myeloma cells
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Concentration:0.016 μM, 0.08 μM, 0.4 μM, 2 μM, 10 μM
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Incubation Time:24 h
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Result:Induced concentration-dependent degradation of HDAC1, with a DC50, 24 h value of 2.55 μM.
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Cell Line:MM.1S multiple myeloma cells
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Concentration:5 μM
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Incubation Time:24 h
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Result:Strongly upregulated Ac-α-tubulin (a known HDAC6 substrate) and upregulated Ac-histone H3 (a class I HDAC substrate), confirming inhibition of HDAC6 and class I HDACs (including HDAC1 and HDAC2) in cells.
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Cell Line:MM.1S multiple myeloma cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Caused robust HDAC1 degradation, while the negative control SZ-2-N (which cannot bind DDB1 covalently) did not induce any HDAC1 degradation at the same concentration.
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Cell Line:MM.1S multiple myeloma cells
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Concentration:5 μM
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Incubation Time:48 h
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Result:Significantly increased the number of early and late apoptotic MM.1S cells, with an apoptotic cell count comparable to that induced by ricolinostat.
Chemical Information
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Appearance Solid
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Molecular Weight 591.10
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Formula C32H35ClN4O5
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SMILES
O=C(NCCCCCCC(NO)=O)C1=CC=C(C2CC(C3=CC=CC(OCC4=CC=CC=C4)=C3)=NN2C(CCl)=O)C=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (169.18 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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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.
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.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
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, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.6918 mL | 8.4588 mL | 16.9176 mL | 42.2940 mL |
| 5 mM | 0.3384 mL | 1.6918 mL | 3.3835 mL | 8.4588 mL | |
| 10 mM | 0.1692 mL | 0.8459 mL | 1.6918 mL | 4.2294 mL | |
| 15 mM | 0.1128 mL | 0.5639 mL | 1.1278 mL | 2.8196 mL | |
| 20 mM | 0.0846 mL | 0.4229 mL | 0.8459 mL | 2.1147 mL | |
| 25 mM | 0.0677 mL | 0.3384 mL | 0.6767 mL | 1.6918 mL | |
| 30 mM | 0.0564 mL | 0.2820 mL | 0.5639 mL | 1.4098 mL | |
| 40 mM | 0.0423 mL | 0.2115 mL | 0.4229 mL | 1.0574 mL | |
| 50 mM | 0.0338 mL | 0.1692 mL | 0.3384 mL | 0.8459 mL | |
| 60 mM | 0.0282 mL | 0.1410 mL | 0.2820 mL | 0.7049 mL | |
| 80 mM | 0.0211 mL | 0.1057 mL | 0.2115 mL | 0.5287 mL | |
| 100 mM | 0.0169 mL | 0.0846 mL | 0.1692 mL | 0.4229 mL |
HDAC degrader-2 Related Classifications
HY-178161 Related Classifications
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