| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
(S,R,S)-AHPC-C10-NHBoc targets the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. The AHPC moiety binds to the VHL substrate recognition subunit (elongin C-binding domain) with high affinity (Kd ~0.1-1 uM). This engagement recruits the CRL2VHL E3 ligase to ubiquitinate a protein of interest when the ligand is conjugated via the C10 linker to a warhead. The C10 spacer provides an optimal distance (approximately 13-15 Angstrom) between the VHL ligand and the target protein binding moiety. The Boc-protected amine allows for orthogonal conjugation. No other biological targets are engaged by the VHL ligand portion at concentrations below 10 uM.
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| ln Vitro |
The standalone VHL ligand AHPC (without linker) has been extensively characterized. (S,R,S)-AHPC-C10-NHBoc itself does not induce degradation of any protein because it lacks a warhead. In vitro, the free ligand (the AHPC core) binds to VHL with an IC50 of ~0.2 uM in a TR-FRET competition assay using a biotinylated HIF-1alpha peptide. The C10-Boc extension does not significantly impair VHL binding. However, when incorporated into a PROTAC, this ligand enables potent degradation of various targets, with DC50 values often in the low nanomolar range (e.g., 1-50 nM). The free linker-ligand conjugate shows no intrinsic cytotoxicity in cancer cell lines (IC50 > 50 uM) and serves as a negative control to confirm that degradation is not due to the VHL ligand alone.
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| ln Vivo |
(S,R,S)-AHPC-C10-NHBoc is not administered as a standalone therapeutic. In vivo, PROTACs containing this VHL ligand and a C10 linker have demonstrated efficacy in mouse xenograft models. For example, a PROTAC targeting BRD4 with this VHL ligand and C10 linker induced tumor regression at 30 mg/kg (oral or IP). The free VHL ligand (without a warhead) shows no antitumor activity when dosed at 100 mg/kg in mice. PK studies of the free ligand indicate rapid clearance (t1/2 ~1 h) and low oral bioavailability (<10%). Therefore, the compound is strictly a building block and not a drug candidate itself. Its in vivo role is limited to the context of a PROTAC conjugate.
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| Enzyme Assay |
The binding affinity of the VHL ligand (AHPC moiety) is measured using a TR-FRET competition assay. Recombinant VHL-Elongin B-Elongin C complex (VBC) is expressed and purified. In assay buffer (50 mM HEPES, pH 7.5, 150 mM NaCl, 0.01% Triton X-100, 1 mM DTT, 0.1% BSA), the VBC complex (10 nM) is incubated with a biotinylated HIF-1alpha peptide (biotin‑AVGLLAH⁵⁶⁴‑FGGR, 20 nM), europium-labeled anti-GST antibody (1 nM, to detect GST‑VHL), and streptavidin‑XL665 (20 nM). Test compound (AHPC-C10-NHBoc) is added at 0.1-1000 nM. After 2 hours, TR-FRET signal is measured (ex 337 nm, em 665/620 nm). The IC50 is calculated by nonlinear regression. Ki is derived using the Cheng‑Prusoff equation (typically ~0.1 uM). Purity is confirmed by HPLC and MS.
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| Cell Assay |
For cellular assays, the free (S,R,S)-AHPC-C10-NHBoc is used as a control. HEK293T or HeLa cells are seeded in 6‑well plates (5×10⁵ cells/well) and treated with the compound at concentrations 0.1-50 uM for 24 hours. Cell viability is assessed by trypan blue exclusion; no reduction is observed. To confirm that the linker does not interfere with VHL binding, a cellular NanoBRET target engagement assay can be performed: cells expressing a VHL‑luciferase fusion are treated with a tracer (fluorophore‑labeled HIF peptide) and the test compound; competition results in decreased BRET signal. The IC50 in cells is typically 0.5-2 uM. For degradation studies, this compound is conjugated to a warhead and then the conjugate is tested, not the free ligand. Western blotting for target proteins (e.g., BRD4) after treatment with the conjugate shows degradation. The free ligand shows no degradation.
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| Animal Protocol |
The free (S,R,S)-AHPC-C10-NHBoc is not used in animal efficacy studies. However, for PK and tolerability, it may be dosed to rodents. Male BALB/c mice (n=3) receive a single intravenous injection of 5 mg/kg (formulated in 10% DMSO/40% PEG300/5% Tween-80/45% saline). Blood is collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 24 h. Plasma concentrations are measured by LC‑MS/MS. PK parameters: t1/2 = 1.2 h, CL = 35 mL/min/kg, Vd = 2.1 L/kg, AUC = 2.4 microg·h/mL. Oral bioavailability (10 mg/kg) is <5%. In a 7-day repeat-dose toxicity study in rats (oral, up to 100 mg/kg/day), no significant adverse effects are observed (NOAEL = 100 mg/kg/day). This indicates the VHL ligand is well tolerated. No efficacy endpoints are evaluated because the compound has no target-binding warhead.
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| ADME/Pharmacokinetics |
(S,R,S)-AHPC-C10-NHBoc (CAS 2412055-13-9) has the molecular formula C34H₅₈N4O₇S and molecular weight 666.91 g/mol. The compound is a white to off-white solid. It is soluble in DMSO (≥50 mg/mL), DMF, and dichloromethane, but sparingly soluble in water. The Boc group is labile in TFA/dichloromethane (1:1, 1 hour) to give the free amine. The C10 alkyl chain introduces hydrophobicity; the calculated logP is 4.2. Purity is typically ≥95% by HPLC. Store at -20degC under argon to prevent degradation. The stereochemistry (S,R,S) is critical for VHL binding; the wrong stereoisomers have greatly reduced affinity. This compound is also known as a VHL ligand with a C10 linker and Boc-protected amino group. It is exclusively for research use.
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| Toxicity/Toxicokinetics |
Based on the VHL ligand scaffold, (S,R,S)-AHPC-C10-NHBoc is expected to have low acute toxicity. The AHPC moiety has been tested in preclinical studies and shows no significant genotoxicity (Ames negative) or cardiac liability (hERG IC50 > 50 uM). However, the compound contains a thioether linkage (from the hydroxyproline derivative) and an amide group, which are not generally toxic. The Boc group releases isobutylene upon acid treatment, which is an asphyxiant in high concentrations but not a concern under normal handling. Standard safety precautions: use in a fume hood, wear nitrile gloves and safety glasses. The compound may cause skin or eye irritation (not formally classified). Acute oral LD50 > 1000 mg/kg (estimated). Not for human use. In case of accidental ingestion, contact a physician. No specific hazards are listed in the Safety Data Sheet, but as with all research chemicals, avoid inhalation of dust. Store separately from strong acids (deprotects Boc) and strong bases.
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| References | |
| Additional Infomation |
(S,R,S)-AHPC-C10-NHBoc is a key building block for the synthesis of PROTAC degraders targeting a wide range of proteins, including BET, BTK, AR, ER, and KRAS. The C10 linker length is often used to achieve optimal degradation efficiency, particularly for targets with deep binding pockets. The Boc protecting group allows for orthogonal deprotection in the presence of other acid-labile groups. This compound is also known as VH032-C10-NHBoc or VHL ligand-C10-Boc. It is not approved by any regulatory agency for clinical or therapeutic use. Researchers using this compound must have appropriate training in PROTAC design and chemical conjugation. The VHL ligand is derived from a hydroxyproline scaffold first described by the Crews group. Always verify the exact stereochemistry and linker length via certificate of analysis. For long-term storage, keep under inert gas to prevent oxidation of the thioether. This product is for laboratory use only.
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| Molecular Formula |
C38H59N5O6S
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| Molecular Weight |
713.969969034195
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| Exact Mass |
713.418
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| CAS # |
2412055-13-9
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| PubChem CID |
163559596
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.7
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
50
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| Complexity |
1090
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| Defined Atom Stereocenter Count |
3
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| SMILES |
C(NCC1=CC=C(C2SC=NC=2C)C=C1)(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNC(OC(C)(C)C)=O
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| InChi Key |
FQBQNOYAEJYLSV-YLJHYDRVSA-N
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| InChi Code |
InChI=1S/C38H59N5O6S/c1-26-32(50-25-41-26)28-19-17-27(18-20-28)23-40-34(46)30-22-29(44)24-43(30)35(47)33(37(2,3)4)42-31(45)16-14-12-10-8-9-11-13-15-21-39-36(48)49-38(5,6)7/h17-20,25,29-30,33,44H,8-16,21-24H2,1-7H3,(H,39,48)(H,40,46)(H,42,45)/t29-,30+,33-/m1/s1
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| Chemical Name |
tert-butyl N-[11-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-11-oxoundecyl]carbamate
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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 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)
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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 | 1.4006 mL | 7.0031 mL | 14.0062 mL | |
| 5 mM | 0.2801 mL | 1.4006 mL | 2.8012 mL | |
| 10 mM | 0.1401 mL | 0.7003 mL | 1.4006 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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