GAL-02-221
Based on 1 Customer Validation
GAL-02-221 is a BRD4 PROTAC degrader with blood-brain barrier permeability, with a DC50 of 0.009 μM (Jurkat BRD4-HiBiT). GAL-02-221 induces proteasome-catalyzed BRD4 degradation, binds to VHL to trigger BRD4 ubiquitination, and recruits the VHL E3 ligase complex to participate in protein degradation. GAL-02-221 degrades BRD4 in breast cancer cells as well as mouse liver and brain tissues. GAL-02-221 is applicable to research related to breast cancer.
(Pink: BRD4 ligand (HY-78695); Blue: VHL ligand (HY-112078); Black: linker (HY-33366)).
For research use only. We do not sell to patients.
- Purity: 99.87%
- CAS No.: 2409538-70-9
- Formula: C50H62ClN9O8S2
- Molecular Weight:1016.67
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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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
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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BRD4 0.009 μM (DC50) |
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Cell Line
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Type | Value | Description | References |
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| CWR22R | EC50 |
90 nM
Compound: 79; ARV-771
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Antiproliferative activity against human 22Rv1 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay
Antiproliferative activity against human 22Rv1 cells assessed as reduction in cell viability incubated for 48 hrs by MTT assay
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[PMID: 38199162] |
| L02 | IC50 |
400 nM
Compound: 1; PRO
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Antiproliferative activity against human L02 cells harboring minimal integrin alphaVbeta3 expression assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human L02 cells harboring minimal integrin alphaVbeta3 expression assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
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[PMID: 38055861] |
| MCF7 | IC50 |
30 nM
Compound: 1; PRO
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Antiproliferative activity against human MCF7 cells harboring low integrin alphaVbeta3 expression assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human MCF7 cells harboring low integrin alphaVbeta3 expression assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
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[PMID: 38055861] |
| MDA-MB-231 | IC50 |
90 nM
Compound: 1; PRO
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Antiproliferative activity against human MDA-MB-231 cells harboring high integrin alphaVbeta3 expression assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
Antiproliferative activity against human MDA-MB-231 cells harboring high integrin alphaVbeta3 expression assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay
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[PMID: 38055861] |
GAL-02-221 (5-100 nM; 4 h continuous incubation, 1 h incubation followed by 23 h washout) induces BRD4 degradation in MCF-7, MDA-MB-231, SK-BR-3 and BT-474 breast cancer cell lines[1].
GAL-02-221 (10-point half-log titration starting at 100 μM; 0.5-2 h) binds to VHL in intact HEK293 cells, with an IC50 of approximately 1.3 μM at both 30 min and 2 h, and no time-dependent change in potency[2].
GAL-02-221 (10-point half-log titration starting at 100 μM; 25 min post-digitonin permeabilization) exhibits enhanced binding potency to the VHL target in digitonin (HY-N4000)-permeabilized HEK293 cells, confirming that cell permeability limits its activity in intact cells[2].
GAL-02-221 (10-point half-log titration starting at 100 μM; 1-5 h) potently degrades BRD4 in Jurkat BRD4-HiBiT cells, with a DC50 of 0.009 μM and a maximum degradation rate of 96% after 5 h of incubation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7, MDA-MB-231, SK-BR-3, BT-474
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Concentration:5, 10, 50, 100 nM
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Incubation Time:4 h (continuous incubation); 1 h incubation followed by 23 h washout
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Result:Induced BRD4 degradation in all tested cell lines.
Showed varying degradation profiles likely related to differential BRD4 expression levels across cell lines.
Demonstrated BRD4 degradation after 4 h of continuous incubation.
Demonstrated BRD4 degradation after a 1 h incubation followed by 23 h washout.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 8-12 weeks, 20-24 g)[2]
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Dosage:10 mg/kg
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Administration:i.v.; single dose
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Result:Reached measurable concentrations of ~20 ng/g in brain tissue at 0.25 hours postdose.
Reached measurable concentrations of ~2 ng/g in brain tissue at 1 hour postdose.
Reached measurable concentrations of ~1 ng/g in brain tissue at 2 hours postdose.
Induced BRD4 degradation in perfused brain tissue at early time points.
Chemical Information
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CAS No. 2409538-70-9
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Appearance Solid
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Molecular Weight 1016.67
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Formula C50H62ClN9O8S2
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Color White to off-white
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SMILES
O=C([C@H]1N(C([C@H](C(C)(C)C)NC(COCCOCCOCCNC(C[C@H]2C3=NN=C(C)N3C4=C(C(C)=C(C)S4)C(C5=CC=C(Cl)C=C5)=N2)=O)=O)=O)C[C@H](O)C1)N[C@H](C6=CC=C(C7=C(C)N=CS7)C=C6)C
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Synonyms
PROTAC BRD4 Degrader-5
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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 2 years -20°C 1 year
Solvent & Solubility
DMSO : 145 mg/mL (142.62 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: ≥ 7.25 mg/mL (7.13 mM); Clear solution
This protocol yields a clear solution of ≥ 7.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (72.5 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: 7.25 mg/mL (7.13 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 7.25 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 (72.5 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:
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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
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Data Sheet (277 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
[1]. Maneiro MA, et al. Antibody-PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4. ACS chemical biology. 2020 Jun 19;15(6):1306-1312. [Content Brief]
[2]. Leconte GA, et al. A Lipid Prodrug Strategy Enhances Targeted Protein Degrader CNS Pharmacokinetics. Journal of medicinal chemistry. 2025 Aug 28;68(16):17339-17349. [Content Brief]
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 | 0.9836 mL | 4.9180 mL | 9.8360 mL | 24.5901 mL |
| 5 mM | 0.1967 mL | 0.9836 mL | 1.9672 mL | 4.9180 mL | |
| 10 mM | 0.0984 mL | 0.4918 mL | 0.9836 mL | 2.4590 mL | |
| 15 mM | 0.0656 mL | 0.3279 mL | 0.6557 mL | 1.6393 mL | |
| 20 mM | 0.0492 mL | 0.2459 mL | 0.4918 mL | 1.2295 mL | |
| 25 mM | 0.0393 mL | 0.1967 mL | 0.3934 mL | 0.9836 mL | |
| 30 mM | 0.0328 mL | 0.1639 mL | 0.3279 mL | 0.8197 mL | |
| 40 mM | 0.0246 mL | 0.1230 mL | 0.2459 mL | 0.6148 mL | |
| 50 mM | 0.0197 mL | 0.0984 mL | 0.1967 mL | 0.4918 mL | |
| 60 mM | 0.0164 mL | 0.0820 mL | 0.1639 mL | 0.4098 mL | |
| 80 mM | 0.0123 mL | 0.0615 mL | 0.1230 mL | 0.3074 mL | |
| 100 mM | 0.0098 mL | 0.0492 mL | 0.0984 mL | 0.2459 mL |
GAL-02-221 Related Classifications
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