| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| Other Sizes |
| Targets |
Bcl-xL
Von Hippel-Lindau (VHL) as a ligand. The C7 ester can be hydrolyzed to a carboxylic acid for further conjugation. |
|---|---|
| ln Vitro |
The (S,R,S)-AHPC-Me core binds VHL with high affinity (Kd ~0.1-1 uM). The N-methyl group may improve metabolic stability and cell permeability. The C7 ester provides a hydrophobic spacer (7 carbons) that can be hydrolyzed to a carboxylic acid (via esterase or basic conditions) for conjugation to target warheads. The compound alone does not degrade proteins; it is a synthetic intermediate.
|
| Cell Assay |
Cells (e.g., HEK293) are treated with the ester form. The ester is likely hydrolyzed intracellularly to the corresponding acid. For PROTAC evaluation, the compound is first deprotected (hydrolyzed) to the free acid, then conjugated to a target binder. The resulting PROTAC is tested for target degradation by Western blot. The intermediate alone shows no degradation activity.
|
| Animal Protocol |
In vivo, PROTACs assembled from this building block are administered to xenograft mice. The C7 alkyl chain may enhance cell permeability and oral bioavailability compared to PEG linkers. The ester group is rapidly hydrolyzed in plasma (t1/2 <30 min) to the active acid. PK of final PROTAC is characterized. The intermediate itself is not dosed.
|
| ADME/Pharmacokinetics |
Molecular weight: approximately 700-800 g/mol. The C7 ester is lipophilic (logP ~4-5). The compound is soluble in DMSO, less so in water. The ester is stored desiccated at -20degC to prevent hydrolysis. Upon exposure to aqueous buffer or serum, the ester is hydrolyzed to the carboxylic acid. The free acid can be used for amide coupling.
|
| Toxicity/Toxicokinetics |
The AHPC-based VHL ligands have low toxicity (LD50 > 1000 mg/kg). The C7 ester and N-methyl group are not expected to increase toxicity. Standard safety precautions apply. The compound is for research only. Avoid inhalation and skin contact. No teratogenicity data specific to VHL ligands, but handle with care.
|
| References | |
| Additional Infomation |
(S,R,S)-AHPC-Me-C7 ester is a specialized PROTAC building block. The C7 alkyl chain provides a longer hydrophobic spacer than C5 or C6. The ester group is a protected carboxylic acid that can be selectively deprotected without affecting other functional groups. The N-methyl modification is less common but may improve drug-like properties. This intermediate is used in the synthesis of VHL-based degraders. No clinical approval.
|
| Molecular Formula |
C32H46N4O6S
|
|---|---|
| Molecular Weight |
614.80
|
| Exact Mass |
614.313
|
| CAS # |
2639528-48-4
|
| PubChem CID |
139600219
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.1
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
15
|
| Heavy Atom Count |
43
|
| Complexity |
951
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
CCOC(=O)CCCCCC(=O)N[C@H](C(=O)N1C[C@@H](C[C@H]1C(=O)N[C@@H](C)C2=CC=C(C=C2)C3=C(N=CS3)C)O)C(C)(C)C
|
| InChi Key |
GQGWVJVMHUOOQE-WEORHZHFSA-N
|
| InChi Code |
InChI=1S/C32H46N4O6S/c1-7-42-27(39)12-10-8-9-11-26(38)35-29(32(4,5)6)31(41)36-18-24(37)17-25(36)30(40)34-20(2)22-13-15-23(16-14-22)28-21(3)33-19-43-28/h13-16,19-20,24-25,29,37H,7-12,17-18H2,1-6H3,(H,34,40)(H,35,38)/t20-,24+,25-,29+/m0/s1
|
| Chemical Name |
ethyl 7-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-7-oxoheptanoate
|
| 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, avoid exposure to moisture. |
| 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) |
DMSO :~6.67 mg/mL (~10.85 mM )
|
|---|---|
| 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 | 1.6265 mL | 8.1327 mL | 16.2655 mL | |
| 5 mM | 0.3253 mL | 1.6265 mL | 3.2531 mL | |
| 10 mM | 0.1627 mL | 0.8133 mL | 1.6265 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
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