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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
The primary target of NVS-CECR2-1 is CECR2, a bromodomain-containing protein. It binds to the CECR2 BRD with high affinity (IC50 = 47 nM; Kd = 80 nM). By inhibiting CECR2, it disrupts chromatin remodeling and transcriptional regulation, leading to anticancer effects. It shows no cross-reactivity in a panel of 48 bromodomain targets or major kinase, protease, and receptor panels.
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| ln Vitro |
NVS-CECR2-1 diminishes all pancreatic viability at 1-4 μM for 72 hours [1]. NVS-CECR2-1 (1-6 μM; 72 hours) was developed to boost mitochondria within cells [1]. In SW48 cells, NVS-CECR2-1 (10 μM; 2 hr) suppresses CECR2 BRD's chromatin binding. Its IC50 value is predicted to be 0.64 μM. NVS-CECR2-1 (0.5–4 μM; 10 days) decreases the clonogenic activity of SW48 cells in a dose-dependent manner. NVS-CECR2-1 (5, 10, 15 μM; 2 hours) cleaves chromatin from chromatin in a linear manner. a distance from CECR2 that doesn't impact BRG1[1]. -CECR2-1 removes CECR2 from intracellular chromatin and prevents the CECR2 BRD from binding to chromatin [1].
In vitro, NVS-CECR2-1 exhibits cytotoxic activity and induces apoptosis against various cancer cells. It inhibits chromatin binding of CECR2 BRD. In SW48 cells, treatment with 1-6 μM for 72 hours has been shown to boost mitochondria within cells. Its selectivity for CECR2 makes it a valuable tool for studying CECR2-specific functions. |
| ln Vivo |
In vivo, NVS-CECR2-1 has antitumor activity. It induces apoptosis in cancer cells through both CECR2-targeting and CECR2-independent mechanisms. While specific in vivo animal model data is not extensively detailed in the available literature, its cytotoxic activity in cancer cells suggests potential efficacy in xenograft models.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for NVS-CECR2-1 involve bromodomain binding assays using recombinant CECR2 BRD protein. The compound's binding affinity is measured using techniques such as fluorescence polarization, AlphaScreen, or surface plasmon resonance (SPR). IC50 and Kd values are determined from binding curves. Selectivity is assessed by profiling against a panel of bromodomains and other protein families.
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| Cell Assay |
Cell viability assay[1]
Cell Types: colon (SW48, HT29 and HCT116), lung (H460), urinary epithelium (SV-HUC-1), cervix (HeLa) and bone (U2OS), human embryonic kidney (HEK) 293 T cell Tested Concentrations: 1, 1.5, 2, 2.5, 3, 4 μM Incubation Duration: 72 hrs (hours) Experimental Results: Viability diminished in all cancer cells analyzed in a dose-dependent manner. demonstrated dose-dependent cytotoxicity against HEK 293 T cells. Apoptosis analysis [1] Cell Types: SW48 cells Tested Concentrations: 0.5, 1, 1.5, 2, 4, 6 μM Incubation Duration: 72 hrs (hours) Experimental Results: Apoptosis increased in a dose-dependent manner, exceeding 80% of cells at 6°C Apoptosis occurs at μM and has little effect on necrosis. In vitro cellular assays for NVS-CECR2-1 are conducted in various cancer cell lines. Cells are treated with the compound, and cell viability is measured using assays such as MTT or CellTiter-Glo to assess cytotoxicity. Apoptosis is evaluated by measuring caspase activation, annexin V staining, or PARP cleavage. The compound's effects on mitochondrial function can be assessed by measuring mitochondrial membrane potential or ATP levels. |
| Animal Protocol |
In vivo animal studies for NVS-CECR2-1 would likely involve mouse xenograft models using cancer cell lines sensitive to the compound. Mice would be administered the compound orally or intraperitoneally, and tumor growth inhibition would be monitored. The compound's ability to induce apoptosis and its effects on CECR2 target engagement in tumors could be assessed by immunohistochemistry or western blotting.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NVS-CECR2-1 indicate it has a molecular weight of 495.68 and a molecular formula of C27H37N5O2S. It is soluble in DMSO. The compound is typically stored as a powder at -20°C. Its oral bioavailability and other PK parameters would be determined in preclinical studies, as it is a research probe for in vivo use.
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| Toxicity/Toxicokinetics |
Toxicological information for NVS-CECR2-1 is limited to preclinical studies. As a bromodomain inhibitor, it may have effects on gene expression and cellular differentiation. Its selectivity for CECR2 over other bromodomains suggests a favorable off-target profile. Comprehensive toxicology studies would be required for clinical development, including assessments of hematological, gastrointestinal, and reproductive toxicity.
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| References | |
| Additional Infomation |
Bromine domain inhibitors
NVS-CECR2-1 is a potent and selective chemical probe for studying CECR2 function in chromatin remodeling and transcriptional regulation. It has antitumor activity and induces apoptosis in cancer cells. The compound is available from research chemical suppliers for preclinical studies. It is not approved for clinical use and is intended for research purposes only. |
| Molecular Formula |
C27H37N5O2S
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|---|---|
| Molecular Weight |
495.68
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| Exact Mass |
495.266
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| CAS # |
1992047-61-6
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| Related CAS # |
1992047-61-6;NVS-CECR2-1 HCl;
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| PubChem CID |
117072550
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
712.7±70.0 °C at 760 mmHg
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| Flash Point |
384.8±35.7 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.659
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| LogP |
4.14
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
836
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCS(=O)(=O)C1=NC(=CC(=N1)NC2CC2)C3=CC4=C(C=C3)N(C=C4)C5CC(NC(C5)(C)C)(C)C
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| InChi Key |
XVECNLUKQDKOST-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H37N5O2S/c1-6-13-35(33,34)25-29-22(15-24(30-25)28-20-8-9-20)18-7-10-23-19(14-18)11-12-32(23)21-16-26(2,3)31-27(4,5)17-21/h7,10-12,14-15,20-21,31H,6,8-9,13,16-17H2,1-5H3,(H,28,29,30)
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| Chemical Name |
N-cyclopropyl-2-propylsulfonyl-6-[1-(2,2,6,6-tetramethylpiperidin-4-yl)indol-5-yl]pyrimidin-4-amine
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| Synonyms |
NVSCECR21 NVS1NVS CECR2 1 NVS-1 NVS 1 NVS-CECR2-1
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~66.67 mg/mL (~134.50 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.04 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 25.0 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 | 2.0174 mL | 10.0872 mL | 20.1743 mL | |
| 5 mM | 0.4035 mL | 2.0174 mL | 4.0349 mL | |
| 10 mM | 0.2017 mL | 1.0087 mL | 2.0174 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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