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| 5mg |
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| Targets |
HaloPROTAC3 targets HaloTag7 fusion proteins for degradation via the proteasomal pathway. It binds to VHL with an IC50 of 0.54 μM. The compound is a conjugate of ligands for E3 ligase (VHL) and a 16-atom-length linker. By forming a ternary complex between the HaloTag fusion protein, HaloPROTAC3, and VHL E3 ligase, it facilitates ubiquitination and subsequent degradation of the HaloTagged protein of interest.
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| ln Vitro |
HaloPROTAC3 is a highly potent and efficacious degrader of GFP-HaloTag7 fusion proteins with a DC50 of 19 nM. At 625 nM, it induces 90% degradation of GFP-HaloTag7. It binds to VHL with an IC50 of 0.54 μM. The compound demonstrates excellent degradation efficacy in cellular models and has been used to study the kinetic degradation profiles of various HaloTag fusion proteins.
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| ln Vivo |
In vivo, HaloPROTAC3 has been used to achieve targeted degradation of HaloTag fusion proteins in cellular and potentially animal models. The kinetics of degradation have been extensively studied, revealing that significant degradation occurs within hours after treatment. It has been employed in antiviral studies, where HaloG3BP1 targeted degradation using HaloPROTAC3 demonstrated antiviral effects against MNV1 infection. The compound's efficacy in vivo depends on the expression of the HaloTag fusion protein target.
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| Enzyme Assay |
Binding affinity of HaloPROTAC3 to VHL is measured using fluorescence polarization or surface plasmon resonance (SPR) assays. Recombinant VHL protein is incubated with a fluorescently labeled VHL ligand probe, and displacement by HaloPROTAC3 at varying concentrations is measured. IC50 values are calculated from competition curves. The assay confirms the compound's ability to engage the VHL E3 ligase with an IC50 of 0.54 μM.
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| Cell Assay |
Degradation activity is evaluated in HEK293 cells expressing GFP-HaloTag7 fusion protein. Cells are treated with HaloPROTAC3 at escalating concentrations (typically 0.1 nM to 10 μM) for 4-24 hours. GFP fluorescence is measured by flow cytometry or fluorescence microscopy to quantify remaining HaloTag7 protein. DC50 values are calculated from dose-response curves. Western blot analysis with anti-HaloTag or anti-GFP antibodies confirms degradation. The kinetics of degradation are assessed at various time points.
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| Animal Protocol |
In vivo studies with HaloPROTAC3 typically involve administration to mouse models expressing HaloTag fusion proteins of interest. The compound can be administered via intraperitoneal injection or other routes. Tissues are collected at various time points post-administration, and HaloTag fusion protein levels are quantified by Western blot or immunohistochemistry. Pharmacodynamic endpoints include assessment of target degradation efficiency and duration of effect.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of HaloPROTAC3 are characteristic of PROTAC molecules. It has a molecular formula of C41H55ClN4O8S and a molecular weight of 799.42. The compound is soluble in DMSO. It should be stored as a solid powder at -20°C for long-term stability or at 0-4°C for short-term use. As a PROTAC, it has a 16-atom linker connecting the HaloTag ligand and VHL ligand.
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| Toxicity/Toxicokinetics |
Toxicological data for HaloPROTAC3 are limited to research applications. The compound is for research use only and not intended for therapeutic use. As a tool compound for targeted protein degradation, toxicity is primarily evaluated in the context of the specific cell lines or animal models being studied. The compound is generally well-tolerated at concentrations used for in vitro degradation studies. Comprehensive toxicology profiling would be required for clinical development.
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| References | |
| Additional Infomation |
HaloPROTAC3 is the prototypical small-molecule VHL-recruiting HaloTag degrader and remains the most widely validated tool for HaloTag fusion protein depletion. It is also known as VH285-PEG4-C4-Cl. The compound enables the study of protein function by inducing degradation of specific HaloTagged proteins of interest. It has been used in diverse applications including receptor pharmacology, antiviral research, and the study of protein degradation kinetics. HaloPROTAC3 provides a chemical biology approach to investigate protein function with temporal control.
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| Molecular Formula |
C41H55CLN4O8S
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|---|---|
| Molecular Weight |
799.4154
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| Exact Mass |
798.34
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| Elemental Analysis |
C, 61.60; H, 6.94; Cl, 4.43; N, 7.01; O, 16.01; S, 4.01
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| CAS # |
1799506-07-2
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| PubChem CID |
156597126
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| Appearance |
Colorless to off-white liquid
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
23
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| Heavy Atom Count |
55
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| Complexity |
1190
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=C(SC=N1)C2=CC(=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)C)N4CC5=CC=CC=C5C4=O)O)OCCOCCOCCOCCCCCCCl
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| InChi Key |
UABTZMQNIWDHGQ-JGNAJVFASA-N
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| InChi Code |
InChI=1S/C41H55ClN4O8S/c1-28(2)37(46-25-32-10-6-7-11-34(32)40(46)49)41(50)45-26-33(47)23-35(45)39(48)43-24-31-13-12-30(38-29(3)44-27-55-38)22-36(31)54-21-20-53-19-18-52-17-16-51-15-9-5-4-8-14-42/h6-7,10-13,22,27-28,33,35,37,47H,4-5,8-9,14-21,23-26H2,1-3H3,(H,43,48)/t33-,35+,37+/m1/s1
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| Chemical Name |
(2S,4R)-N-(2-(2-(2-(2-((6-Chlorohexyl)oxy)ethoxy)ethoxy)ethoxy)-4-(4-methylthiazol-5-yl)benzyl)-4-hydroxy-1-((S)-3-methyl-2-(1-oxoisoindolin-2-yl)butanoyl)pyrrolidine-2-carboxamide
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| Synonyms |
HaloPROTAC-3; HaloPROTAC 3; Halo PROTAC-3; HaloPROTAC3
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2509 mL | 6.2545 mL | 12.5091 mL | |
| 5 mM | 0.2502 mL | 1.2509 mL | 2.5018 mL | |
| 10 mM | 0.1251 mL | 0.6255 mL | 1.2509 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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