Name: NV03
Brand: BOC Sciences
Rating: 5 (1 reviews)

Purity

95%

Appearance

Solid

Storage

Store at -20°C

IUPACName

N-[3-(diethylamino)propyl]-2-(7,12-dimethyl-9-oxo-5-thia-1,10,11-triazatricyclo[6.4.0.02,6]dodeca-2(6),3,7,11-tetraen-10-yl)acetamide

Synonyms

N-(3-(Diethylamino)propyl)-2-(5,9-dimethyl-8-oxothieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazin-7(8H)-yl)acetamide; Thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine-7(8H)-acetamide, N-[3-(diethylamino)propyl]-5,9-dimethyl-8-oxo-

Density

1.29±0.1 g/cm3 (Predicted)

InChI Key

KNZQAVKYBBYDKV-UHFFFAOYSA-N

InChI

InChI=1S/C19H27N5O2S/c1-5-22(6-2)10-7-9-20-16(25)12-23-19(26)17-13(3)18-15(8-11-27-18)24(17)14(4)21-23/h8,11H,5-7,9-10,12H2,1-4H3,(H,20,25)

Canonical SMILES

CCN(CC)CCCNC(=O)CN1C(=O)C2=C(C3=C(N2C(=N1)C)C=CS3)C

Background Introduction

NV03 is a specialized ligand designed for high-affinity binding to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase complex. VHL ligands are essential tools in the targeted protein degradation field, particularly for the development of PROTACs that leverage the ubiquitin-proteasome system to induce selective degradation of disease-causing proteins. NV03 features an optimized scaffold and functionalized linker attachment site, allowing effective and flexible PROTAC synthesis for both preclinical and translational research.

Mechanism

NV03 operates as a VHL E3 ligase ligand, engaging the VHL component within the CUL2-VHL E3 ubiquitin ligase complex. By binding to VHL, NV03 facilitates the recruitment of an E3 ligase to a designated target protein via a bifunctional PROTAC molecule. This induced proximity leads to ubiquitination of the target protein and its subsequent degradation by the cellular proteasome. The chemical structure of NV03 supports efficient conjugation to various linkers and target warheads for tailored degrader design, ensuring high selectivity and potency.

Applications

NV03 serves as a foundational reagent for the development of VHL-based PROTACs and targeted protein degraders. Key applications include:

• Synthesis of bifunctional VHL-recruiting PROTACs for protein of interest (POI) degradation in oncology, neurology, and other therapeutic research fields.
• Use in SAR studies and medicinal chemistry campaigns to optimize degrader efficacy and selectivity.
• Customization for academic and industrial drug discovery pipelines, enabling rapid exploration of novel chemical space for TPD modalities.
• Application in mechanism-of-action and target validation experiments via selective knockdown of proteins in cell-based and in vivo models. NV03 empowers researchers to drive innovation in targeted protein degradation and next-generation therapeutics.

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Optimized binder for VHL E3 ligase facilitates efficient protein degradation in PROTAC applications.
• High chemical stability and purity support reliable synthesis of next-generation targeted protein degraders.

1. Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain

Hailong Zhang, Guoliang Xun, En Li, Cheryl H Arrowsmith, Hugh Y Zhu, Peter J Brown, Wen Xiao, Irene Chau, Chunliang Lu, Abdellah Allali-Hassani, Counde Oyang, Xiao Luo, Kehao Zhao, Guillermo Senisterra, Peter Atadja, Taraneh Hajian, Fengling Li, Peter Loppnau, Zhengtian Yu, Masoud Vedadi SLAS Discov . 2018 Oct;23(9):930-940. doi: 10.1177/2472555218766278.

Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a multidomain protein that plays a critical role in maintaining DNA methylation patterns through concurrent recognition of hemimethylated DNA and histone marks by various domains, and recruitment of DNA methyltransferase 1 (DNMT1). UHRF1 is overexpressed in various cancers, including breast cancer. The tandem tudor domain (TTD) of UHRF1 specifically and tightly binds to histone H3 di- or trimethylated at lysine 9 (H3K9me2 or H3K9me3, respectively), and this binding is essential for UHRF1 function. We developed an H3K9me3 peptide displacement assay, which was used to screen a library of 44,000 compounds for small molecules that disrupt the UHRF1-H3K9me3 interaction. This screen resulted in the identification of NV01, which bound to UHRF1-TTD with a Kdvalue of 5 μM. The structure of UHRF1-TTD in complex with NV01 confirmed binding to the H3K9me3-binding pocket. Limited structure-based optimization of NV01 led to the discovery of NV03 (Kdof 2.4 μM). These well-characterized small-molecule antagonists of the UHRF1-H3K9me2/3 interaction could be valuable starting chemical matter for developing more potent and cell-active probes toward further characterizing UHRF1 function, with possible applications as anticancer therapeutics.

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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