Name: VH 032-linker 6
Brand: BOC Sciences
Price: 1099 USD
Availability: MadeToOrder

Purity

≥98%

ShelfLife

2 years

Storage

-20°C

IUPACName

(2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Synonyms

VH032-PEG3-acetylene; (2S,4R)-1-((S)-2-(tert-Butyl)-4-oxo-6,9,12-trioxa-3-azapentadec-14-yn-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

InChI Key

HHXQNDSXTCIWSG-CERRFVOPSA-N

InChI

InChI=1S/C31H42N4O7S/c1-6-11-40-12-13-41-14-15-42-19-26(37)34-28(31(3,4)5)30(39)35-18-24(36)16-25(35)29(38)32-17-22-7-9-23(10-8-22)27-21(2)33-20-43-27/h1,7-10,20,24-25,28,36H,11-19H2,2-5H3,(H,32,38)(H,34,37)/t24-,25+,28-/m1/s1

SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)COCCOCCOCC#C)O

Background Introduction

VH 032-linker 6 is a specialized E3 ligase ligand-linker conjugate designed for use in PROTAC (Proteolysis Targeting Chimera) drug development. It is based on the widely studied VH032 ligand, which selectively binds to the von Hippel-Lindau (VHL) E3 ubiquitin ligase—a key component for targeted protein degradation strategies. The addition of a tailored linker moiety enables effective conjugation to various target protein ligands, making VH 032-linker 6 an essential building block for next-generation chemical biology tools and therapeutic agents.

Mechanism

VH 032-linker 6 works by harnessing the natural protein degradation pathway of the ubiquitin-proteasome system. The VH032 moiety specifically binds to the VHL E3 ubiquitin ligase, while the attached linker provides a customizable functional handle. When incorporated into bifunctional PROTAC molecules, VH 032-linker 6 allows the simultaneous recruitment of VHL and a protein of interest. This brings the target protein into proximity with the E3 ligase, facilitating ubiquitination and subsequent proteasomal degradation, thereby selectively removing disease-causing or unwanted proteins from the cell.

Applications

VH 032-linker 6 is utilized extensively in PROTAC molecule synthesis, especially for targeting 'undruggable' proteins in oncology, neurodegenerative, and autoimmune diseases. It enables researchers to design and optimize bifunctional degraders for high-throughput screening, mechanistic studies, and preclinical drug discovery. Furthermore, VH 032-linker 6 is ideal for developing tool compounds for studying protein function, validating therapeutic targets, and advancing structure-activity relationship (SAR) analyses within the rapidly evolving field of targeted protein degradation.

• Potent VHL ligand ensures efficient recruitment of the E3 ubiquitin ligase complex for targeted protein degradation.
• Versatile linker arm allows flexible PROTAC design, enabling rapid development of novel protein degraders with enhanced selectivity.

1. Pharmacokinetics of heroin and its metabolites in vitreous humor and blood in a living pig model

André Gottås, Marianne Arnestad, Gudrun Høiseth, Per Steinar Halvorsen, Liliana C Bachs Forensic Toxicol . 2016;34(2):277-285. doi: 10.1007/s11419-016-0315-z.

Vitreous humor (VH) is an alternative matrix for drug analysis in forensic toxicology. However, little is known about the distribution of xenobiotics, such as opioids, into VH in living organisms. The aim of this study was to simultaneously measure heroin and metabolite concentrations in blood and VH after injection of heroin in a living pig model. Six pigs were under non-opioid anesthesia during the surgical operation and experiment. Ocular microdialysis was used to acquire dialysate from VH, and a venous catheter was used for blood sampling. Twenty milligrams of heroin was injected intravenously with subsequent sampling of blood and dialysate for 6 h. The samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Heroin was not detected in VH; 6-monoacetylmorphine (6-MAM) and morphine were first detected in VH after 60 min. The morphine concentration in VH thereafter increased throughout the experimental period. For 6-MAM,Cmaxwas reached after 230 min in VH. In blood, 6-MAM reachedCmaxafter 0.5 min, with a subsequent biphasic elimination phase. The blood and VH 6-MAM concentrations reached equilibrium after 2 h. In blood, morphine reachedCmaxafter 4.3 min, with a subsequent slower elimination than 6-MAM. The blood and VH morphine concentrations were in equilibrium about 6 h after injection of heroin. In conclusion, both 6-MAM and morphine showed slow transport into VH; detection of 6-MAM in VH did not necessarily reflect a recent intake of heroin. Because postmortem changes are expected to be small in VH, these experimental results could assist the interpretation of heroin deaths.

2. Prevalence, Determinants, and Consequences of Vestibular Hypofunction. Results From the KORA-FF4 Survey

Klaus Jahn, Ralf Strobl, Rolf Holle, Eva Grill, Nadine Lehnen, Erich Schneider, Annette Peters, Karl-Heinz Ladwig, Maria Heuberger, Birgit Linkohr, Murat Saglam Front Neurol . 2018 Dec 7;9:1076. doi: 10.3389/fneur.2018.01076.

Objective:Uni- or bilateral vestibular hypofunction (VH) impairs balance and mobility, and may specifically lead to injury from falls and to disability. The extent of this problem in the general population is still unknown and most likely to be underestimated. Objective of this study was to determine the prevalence, determinants, and consequences of VH in the general population.Methods:Data originates from the cross-sectional second follow-up (FF4) in 2013/14 of the KORA (Cooperative Health Research in the Region of Augsburg)-S4 study (1999-2001) from Southern Germany. This was a random sample of the target population consisting of all residents of the region aged 25-74 years in 1999. We included all participants who reported moderate or severe vertigo or dizziness during the last 12 months and a random sub-sample of participants representative for the general population without vertigo or dizziness during the last 12 months were tested. VH was assessed with the Video-Head Impulse Test (vHIT). Trained examiners applied high-acceleration, small-amplitude passive head rotations ("head impulses") to the left and right in the plane of the horizontal semicircular canals while participants fixated a target straight ahead. During head impulses, head movements were measured with inertial sensors, eye movements with video-oculography (EyeSeeCam vHIT).Results:A total of 2,279 participants were included (mean age 60.8 years, 51.6% female), 570 (25.0%) with moderate or severe vertigo or dizziness during the last 12 months. Of these, 450 were assessed with vHIT where 26 (5.8%) had unilateral VH, and 16 (3.6%) had bilateral VH. Likewise, 190 asymptomatic participants were tested. Of these 5 (2.6%) had unilateral VH, and 2 (1.1%) had bilateral VH. Prevalence of uni- or bilateral VH among tested symptomatic participants was 2.4% in those < 48 years, and 32.1% in individuals aged 79 and over. Age-adjusted prevalence was 6.7% (95% CI 4.8%; 8.6%). VH was associated with worse health, falls, hearing loss, hearing impairment, and ear pressure.Conclusion:VH may affect between 53 and 95 million adults in Europe and the US. While not all affected persons will experience the full spectrum of symptoms and consequences, adequate diagnostic and therapeutic measures should become standard of care to decrease the burden of disease.

3. Factors contributing to coronavirus disease 2019 vaccine hesitancy among healthcare workers in Iran: A descriptive-analytical study

Mehran Taherkhani, Mohammadreza Dinmohammadi, Sakineh Mohammadi, Mohammad Ali Yadegary Clin Epidemiol Glob Health . 2022 Nov-Dec;18:101182. doi: 10.1016/j.cegh.2022.101182.

Background:Despite the easy availability of coronavirus disease 2019 (COVID-19) vaccination services for healthcare workers (HCWs), some of them hesitate about receiving the vaccine. The aim of this study was to assess the factors contributing to COVID-19 vaccine hesitancy (VH) among HCWs in Iran.Methods:This cross-sectional descriptive-analytical study was conducted in 2021-2022. Participants were 551 HCWs selected through systematic random sampling from four leading university hospitals in Zanjan, Iran. A demographic questionnaire and a 36-item COVID-19 VH questionnaire were used for data collection. Data were analyzed using the SPSS software (v. 20) and through the independent-samplet-test, the one-way analysis of variance, and the multiple linear regression analysis.Findings:Participants' age mean was 34.40 ± 7.77 years and most of them were female (65.9%) and married (70.8%) and had university education (88.6%). The mean score of VH was 96.29 ± 12.88 (in the possible range of 36-180), 79.49% of participants had moderate VH, and 17.42% of them had high VH. COVID-19 VH had significant relationship with organizational role, history of chronic disease, COVID-19-related knowledge, history of COVID-19 vaccination, and history of colleagues' or relatives' death after vaccination (P < 0.05). The significant predictors of COVID-19 VH were COVID-19-related knowledge (ß = -0.113; P = 0.008) and history of COVID-19 vaccination (β = 0.165; P < 0.001).Conclusion:COVID-19 VH among HCWs is moderate to high, nurses have the highest VH, and the significant predictors of VH are COVID-19-related knowledge and history of COVID-19 vaccination.

The VH 032-linker 6 E3 Ligase Ligand-Linker Conjugate plays a crucial role in the development of PROTACs by facilitating targeted protein degradation. This molecule combines the specificity of the VH 032 ligand with a versatile linker, enabling efficient recruitment of the E3 ligase to the target protein. The following provides a detailed description of this molecule.

Linker: The linker in VH 032-linker 6 is a flexible, medium-length polyethylene glycol (PEG) chain, allowing for optimal spatial arrangement between the ligand and the target protein. Its non-cleavable nature ensures stability and maintains the integrity of the PROTAC molecule during the degradation process.

Ligand: The ligand component of this conjugate is derived from VH 032, a potent and selective small molecule that binds the VHL E3 ligase. Its structural characteristics include a high affinity for the E3 ligase, ensuring effective recruitment and ubiquitination of the target protein.

Reactive Site: The reactive site in VH 032-linker 6 is designed for conjugation with target protein ligands through an amide bond formation. This site is compatible with nucleophilic groups, such as amines, facilitating robust and stable covalent linkage in the PROTAC assembly.

Recommended Target Protein Ligand: A suitable warhead for this molecule would be a small molecule inhibitor with a reactive amine group, which allows for efficient conjugation via the reactive site. This setup offers the advantage of selective degradation of the target protein, enhancing the potential for therapeutic applications and mechanistic studies in cellular environments. Researchers can utilize this conjugate in experiments focused on elucidating protein function and validating drug targets.

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂