| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
VHL
VHL (Von Hippel-Lindau) E3 ubiquitin ligase; (S,R,S)-AHPC-based VHL complex ligand; E3 Ligase Ligand-Linker Conjugates. |
|---|---|
| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[2].
As a VHL-binding ligand, this compound engages the VHL E3 ubiquitin ligase machinery to facilitate targeted protein degradation via the ubiquitin-proteasome system. No direct data; analogous VHL ligands (e.g., (S,R,S)-AHPC) exhibit high-affinity binding (KD in the low nM range). |
| ln Vivo |
No direct in vivo data; as a functionalized E3 ligase ligand-linker conjugate, it is expected to exhibit similar pharmacokinetic and pharmacological profiles as its parent VHL ligand in PROTAC-based in vivo models.
|
| Enzyme Assay |
Binding affinity is typically evaluated using surface plasmon resonance (SPR) or fluorescence polarization (FP) assays with purified recombinant VHL-elongin B-elongin C complex and immobilized compound. Isothermal titration calorimetry (ITC) is also used to measure thermodynamic binding parameters.
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| Cell Assay |
(1) Cell seeding: plate cells in 96-well plates at 5,000-10,000 cells/well; (2) Compound treatment: incubate with gradient concentrations of the compound (0.1 nM - 10 microM) for 24-72 hours; (3) Viability assay: add CCK-8 or MTT reagent; (4) Apoptosis detection: stain with Annexin V-FITC/PI for flow cytometry; (5) Protein analysis: perform Western blot to assess degradation of target proteins via PROTAC mechanism.
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| Animal Protocol |
(1) Animal selection: use 6-8 week-old BALB/c nude mice; (2) Dosing: administer compound intraperitoneally or orally at 1-100 mg/kg body weight; (3) Formulation: dissolve in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline as a clear injection solution; (4) Sampling: collect blood and tissues at predetermined time points post-dose; (5) Analysis: determine compound concentration in plasma and tissues by LC-MS/MS.
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| ADME/Pharmacokinetics |
Standard formulation includes DMSO as a stock solution mixed with PEG300, Tween 80, and saline (e.g., 10:40:5:45) for injection. Administration routes include intraperitoneal (IP), intravenous (IV), intramuscular (IM), or subcutaneous (SC). PK parameters include half-life (t1/2), maximum concentration (Cmax), and area under the curve (AUC).
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| Toxicity/Toxicokinetics |
For in vitro toxicity, cytotoxicity is tested using CCK-8 on various cell lines including HEK293 and HepG2. For in vivo toxicity, maximum tolerated dose (MTD) studies are performed in rodents. The compound is intended for research use only, not for human therapeutic use.
|
| References |
[1]. Scheepstra M, et al. Bivalent Ligands for Protein Degradation in Drug Discovery. Comput Struct Biotechnol J. 2019;17:160-176. Published 2019 Jan 25.
[2]. Nalawansha DA, et al. PROTACs: An Emerging Therapeutic Modality in Precision Medicine. Cell Chem Biol. 2020;27(8):998-985. |
| Additional Infomation |
(S,R,S)-AHPC-C1-NH2 hydrochloride is an E3 ligase ligand-linker conjugate specifically designed for use in PROTAC synthesis, incorporating the high-affinity VHL ligand (S,R,S)-AHPC. The terminal amine group allows conjugation with various warheads for targeted protein degradation studies. This product is for research use only, not for human use.
|
| Molecular Formula |
C24H34CLN5O4S
|
|---|---|
| Molecular Weight |
524.075863361359
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| Exact Mass |
523.202
|
| CAS # |
2361120-26-3
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| Related CAS # |
(S,R,S)-AHPC-C1-NH2;2010986-20-4
|
| PubChem CID |
155292695
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| Appearance |
Off-white to light yellow solid powder
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
35
|
| Complexity |
737
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
Cl.S1C=NC(C)=C1C1C=CC(=CC=1)CNC([C@@H]1C[C@H](CN1C([C@H](C(C)(C)C)NC(CN)=O)=O)O)=O
|
| InChi Key |
RDVLBRLCBGVZQV-UTYHKCQPSA-N
|
| InChi Code |
InChI=1S/C24H33N5O4S.ClH/c1-14-20(34-13-27-14)16-7-5-15(6-8-16)11-26-22(32)18-9-17(30)12-29(18)23(33)21(24(2,3)4)28-19(31)10-25;/h5-8,13,17-18,21,30H,9-12,25H2,1-4H3,(H,26,32)(H,28,31);1H/t17-,18+,21-;/m1./s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-[(2-aminoacetyl)amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide;hydrochloride
|
| 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 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 :~125 mg/mL (~238.51 mM)
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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 | 1.9081 mL | 9.5405 mL | 19.0811 mL | |
| 5 mM | 0.3816 mL | 1.9081 mL | 3.8162 mL | |
| 10 mM | 0.1908 mL | 0.9541 mL | 1.9081 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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