| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
This compound functions as a recruiting ligand for the E3 ubiquitin ligase Cereblon (CRBN). The (S,R,S)-AHPC motif (a derivative of Lenalidomide/Thalidomide) binds specifically to CRBN. In a complete PROTAC molecule, the target protein ligand is attached to the functional group of this linker. Once the complete PROTAC binds to both the target protein (e.g., BRD4) and CRBN, the ligase is recruited, leading to ubiquitination and subsequent proteasomal degradation of the target protein.
|
|---|---|
| ln Vitro |
The compound is a synthetic intermediate; therefore, its in vitro activity is measured by its ability to participate in click chemistry or conjugation reactions to form a functional PROTAC, rather than direct pharmacological activity. The complete PROTAC BRD4 Degrader-12 demonstrates potent degradation of BRD4 in cellular assays, with DC50 values in the low nanomolar range. This intermediate itself may have low cell permeability due to the TFA salt and long alkyl chain.
|
| ln Vivo |
The intermediate itself has no in vivo activity. The complete PROTAC molecule, BRD4 Degrader-12, has been evaluated in murine models of BET-dependent cancers. When administered intravenously or intraperitoneally, functional PROTACs demonstrate significant tumor growth inhibition (TGI) by reducing BRD4 protein levels in the tumor tissue. This specific linker-ligand conjugate is used as a starting material for synthesizing such in vivo-active molecules.
|
| Enzyme Assay |
No cell-free assays are performed on this intermediate. For the development of the final PROTAC molecule, biochemical assays such as TR-FRET (time-resolved fluorescence resonance energy transfer) are used to measure the binding affinity of the target protein ligand (e.g., to BRD4). Additionally, the binding of the AHPC ligand to CRBN can be confirmed by surface plasmon resonance (SPR) using recombinant CRBN protein.
|
| Cell Assay |
The intermediate is not tested directly in cells. The cellular activity is validated using the final PROTAC. For example, HeLa or 293T cells are transfected with a BRD4-GFP fusion protein. The cells are treated with the complete PROTAC (0.1-1000 nM) for 4-24 hours. The reduction of GFP signal (by Western blot or fluorescence microscopy) indicates degradation. This intermediate is a tool for researchers to synthesize the active molecule.
|
| Animal Protocol |
The intermediate is not intended for direct in vivo administration. The final PROTAC degrader is typically formulated in a vehicle containing a high percentage of PEG300, Tween-80, and saline (e.g., 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline). In animal studies, it is administered intraperitoneally (IP) at doses ranging from 10-50 mg/kg to observe pharmacodynamic effects on target protein degradation in tissues.
|
| ADME/Pharmacokinetics |
The TFA salt form is often used to improve the solubility of the amine-terminated intermediate, which is otherwise poorly soluble in water. The compound has a high molecular weight (MW 924.12). As a heterobifunctional intermediate, its own PK profile (e.g., half-life, clearance) is not characterized, as these properties are only relevant for the final, complete PROTAC molecule.
|
| Toxicity/Toxicokinetics |
This is a research-grade chemical (RUO) and is not intended for human therapeutic use. As a reactive intermediate (containing a methanesulfonothioate leaving group), it may be reactive and should be handled with care in a chemical fume hood. The ligand moiety, AHPC, is a known derivative of immunomodulatory drugs (IMiDs), which carry potential risks of teratogenicity and thrombocytopenia; safety precautions should be taken during handling.
|
| References |
[1]. Dragovich PS, et al. Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy. J Med Chem. 2021 Mar 11;64(5):2576-2607.
|
| Additional Infomation |
(S,R,S)-AHPC-isobutyl acetate-methanesulfonothioate-Me-C10-NH2 TFA is a highly specialized research tool for the field of targeted protein degradation (TPD) using PROteolysis TArgeting Chimeras (PROTACs). It exemplifies the modular synthesis of degraders, where an E3 ligase ligand is attached to a flexible linker. This product is not a drug itself and has no FDA approval; it is strictly for research and development purposes.
|
| Molecular Formula |
C40H60F3N5O10S3
|
|---|---|
| Molecular Weight |
924.12
|
| Appearance |
Typically exists as solid at room temperature
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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 | 1.0821 mL | 5.4106 mL | 10.8211 mL | |
| 5 mM | 0.2164 mL | 1.0821 mL | 2.1642 mL | |
| 10 mM | 0.1082 mL | 0.5411 mL | 1.0821 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
