| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
| Targets |
DCN1
NAcM-OPT targets the protein-protein interaction between N-acetylated UBE2M (UBC12) and DCN1 (defective in cullin neddylation 1). DCN1 is a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. By disrupting the DCN1-UBE2M interaction, NAcM-OPT effectively inhibits the neddylation of cullins, leading to a modulation of cullin-RING ligase (CRL) activity. Cullin neddylation is a critical post-translational modification required for the full activity of CRL E3 ubiquitin ligases, which regulate the turnover of numerous proteins involved in cell cycle, DNA repair, and signal transduction. By blocking this interaction, NAcM-OPT selectively targets the NEDD8/CUL pathway. |
|---|---|
| ln Vitro |
Currently being used to investigate the effects of acute pharmacologic inhibition of the DCN1-UBE2M interaction on the NEDD8/CUL pathway, NAcM-OPT (Compound 67) is orally bioavailable and well tolerated in mice[1].
In vitro, NAcM-OPT potently inhibits the DCN1-UBE2M interaction with an IC₅₀ of 79 nM. It inhibits neddylation in cells and prevents anchorage-independent growth of a DCN1-amplified cell line without causing changes in protein homeostasis. NAcM-OPT (10 µM) reduces cullin 1 NEDDylation levels. It also protects keratinocytes from H₂O₂-induced oxidative damage by promoting autophagy. In a renal fibrosis study, NAcM-OPT was used to demonstrate that blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis in vitro. |
| ln Vivo |
In vivo, NAcM-OPT is an orally bioavailable DCN1 inhibitor. It has been used in animal studies to demonstrate that blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis in vivo, suggesting a novel therapeutic strategy for renal fibrosis. The glucose-responsive p53 degradation mediated by CRL4COP1 can be reversed by the neddylation inhibitor NAcM-OPT, suggesting that CRL4COP1 can be a targetable vulnerability for overnutrition-associated cancer.
|
| Enzyme Assay |
In vitro biochemical assays for NAcM-OPT typically involve time-resolved FRET (TR-FRET) assays to measure the inhibition of the DCN1-UBE2M interaction. Recombinant proteins are incubated with varying concentrations of NAcM-OPT, and the extent of interaction is measured. IC₅₀ values are calculated from dose-response curves. Selectivity assays are performed against DCNL2, DCNL3, DCNL4, and DCNL5. The compound's ability to inhibit neddylation can be assessed by Western blotting for NEDD8-conjugated cullins in cell lysates.
|
| Cell Assay |
For cell-based assays, relevant cell lines (e.g., HK-2 human renal tubular epithelial cells, NRK-49F rat kidney fibroblasts, keratinocytes, or DCN1-amplified cancer cell lines) are cultured in appropriate media. Cells are treated with NAcM-OPT at various concentrations (typically 1-50 µM) for defined periods. The effects on neddylation are assessed by Western blotting for NEDD8-conjugated cullins. Cell viability and proliferation are measured using standard assays such as MTT or CellTiter-Glo. Anchorage-independent growth is assessed by soft agar assays. Autophagy markers can be assessed by Western blotting for LC3-II and p62.
|
| Animal Protocol |
In vivo, NAcM-OPT is typically administered orally to rodents. The compound is formulated in suitable vehicles such as 5% DMSO/40% PEG300/5% Tween 80/50% ddH₂O for injection (4.35 mg/mL) or CMC-Na for oral administration (≥5 mg/mL homogeneous suspension). For renal fibrosis models (e.g., unilateral ureteral obstruction or unilateral ischemia-reperfusion injury), animals are treated with NAcM-OPT at various doses. Endpoints include histological assessment of fibrosis, collagen deposition, and analysis of neddylation and signaling pathways in kidney tissue.
|
| ADME/Pharmacokinetics |
NAcM-OPT (MW 434.40, C₂₃H₂₉Cl₂N₃O) is a solid compound. It is soluble in DMSO (87 mg/mL), ethanol (87 mg/mL), but insoluble in water. Purity: ≥98%. Storage: -20°C for up to 3 years as powder. For oral administration: homogeneous suspension in CMC-Na at ≥5 mg/mL. For injection: 5% DMSO/40% PEG300/5% Tween 80/50% ddH₂O at 4.35 mg/mL.
|
| Toxicity/Toxicokinetics |
NAcM-OPT is for research use only and is not intended for human therapeutic applications. Toxicity data are limited to in vitro and in vivo studies. The compound has been used in animal models at various doses without significant reported toxicity. Standard safety pharmacology and toxicology studies would be required for therapeutic development.
|
| References | |
| Additional Infomation |
1-Benzyl-1-(1-Butyl-4-piperidinyl)-3-(3,4-dichlorophenyl)urea is a type of urea compound.
NAcM-OPT is a research-grade chemical probe for studying neddylation, the ubiquitin-proteasome system, and cullin-RING ligase function. Its primary applications include cancer research, renal fibrosis research, and drug discovery. The compound is not an approved drug and has not entered clinical trials. It is commercially available from various chemical suppliers for research purposes only. Its mechanism involves selective inhibition of the DCN1-UBE2M interaction, blocking cullin neddylation and modulating CRL activity. NAcM-OPT has been shown to reverse glucose-responsive p53 degradation by inhibiting neddylation of CRL4COP1. |
| Molecular Formula |
C23H29CL2N3O
|
|---|---|
| Molecular Weight |
434.4018638134
|
| Exact Mass |
433.168
|
| Elemental Analysis |
C, 63.59; H, 6.73; Cl, 16.32; N, 9.67; O, 3.68
|
| CAS # |
2089293-61-6
|
| Related CAS # |
2089293-61-6;
|
| PubChem CID |
126711307
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
29
|
| Complexity |
493
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCCCN1CCC(CC1)N(CC2=CC=CC=C2)C(=O)NC3=CC(=C(C=C3)Cl)Cl
|
| InChi Key |
VPHJABWIKCBGMC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H29Cl2N3O/c1-2-3-13-27-14-11-20(12-15-27)28(17-18-7-5-4-6-8-18)23(29)26-19-9-10-21(24)22(25)16-19/h4-10,16,20H,2-3,11-15,17H2,1H3,(H,26,29)
|
| Chemical Name |
1-benzyl-1-(1-butylpiperidin-4-yl)-3-(3,4-dichlorophenyl)urea
|
| Synonyms |
NAcM-OPT; NAcM OPT; NAcMOPT;
|
| 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 |
| 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 : 87~125 mg/mL ( 200.27~287.75 )
Ethanol : ~87 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3020 mL | 11.5101 mL | 23.0203 mL | |
| 5 mM | 0.4604 mL | 2.3020 mL | 4.6041 mL | |
| 10 mM | 0.2302 mL | 1.1510 mL | 2.3020 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
