1949837-12-0
1949837-12-0 structure
- Name: ARV-771
- Chemical Name: ARV-771
- CAS Number: 1949837-12-0
- Molecular Formula: C49H60ClN9O7S2
- Molecular Weight: 986.640
- Catalog: Signaling Pathways Epigenetics Epigenetic Reader Domain
- Create Date: 2018-02-21 19:46:19
- Modify Date: 2024-01-08 14:59:09
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ARV-771 is a potent bromodomain and extra-terminal (BET) proteins degrader based on PROTAC technology with Kd values of 4.7, 7.6, 7.6 nM against BRD2, BRD3 and BRD4, respectively.
| Name | ARV-771 |
|---|---|
| Synonyms |
N-({3-[2-({[(6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetyl}amino)ethoxy]propoxy}acetyl)-3-methyl-L-valyl-(4R)-4-hydroxy-N-{(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide
L-Prolinamide, N-[2-[3-[2-[[2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetyl]amino]ethoxy]propoxy]acetyl]-3-methyl-L-valyl-4-hydroxy-N-[(1S)-1-[4-(4-methyl-5-thiazolyl)phenyl]ethyl]-, (4R)- |
| Description | ARV-771 is a potent bromodomain and extra-terminal (BET) proteins degrader based on PROTAC technology with Kd values of 4.7, 7.6, 7.6 nM against BRD2, BRD3 and BRD4, respectively. |
|---|---|
| Related Catalog | |
| Target |
Kd: 4.7 nM (BRD2), 7.6 nM (BRD3), 7.6 nM (BRD4)[1] IC50: <1 nM (c-MYC protein)[1] |
| In Vitro | ARV-771, a small-molecule pan-BET degrader based on proteolysis-targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. ARV-771 potently degrades BRD2/3/4 in 22Rv1 cells with a DC50 less than 5 nM. c-MYC protein is a downstream effector of BET proteins. Treatment with ARV-771 results in depletion of c-MYC with an IC50 of less than 1 nM. ARV-771 shows strong antiproliferative effect on 22Rv1, VCaP, and LnCaP95 cell lines. ARV-771 treatment has a pronounced effect on cell morphology consistent with apoptosis. FL-AR and AR-V7 mRNA are down-regulated upon treatment with 10 nM ARV-771 in VCaP cells. ARV-771 has an antiandrogenic effect on a number of AR-regulated genes in VCaP cells[1]. |
| In Vivo | Treatment of non castrated male Nu/Nu mice bearing AR-V7+ 22Rv1 tumor xenografts with daily subcutaneous injections of ARV-771 at 10 mg/kg for 3 d results in 37% and 76% down-regulation of BRD4 and c-MYC levels, respectively, in tumor tissue. A marked down-regulation in levels of AR-V7 is observed in the 22Rv1 tumors after ARV-771 treatment[1]. |
| Cell Assay | ARV-771 is dissolved in DMSO. 22Rv1 cells (5,000 cells per well) are dosed with ARV-771 serially diluted 1:3 for a 10-point dose curve for 72 h. CellTiter-Glo Luminescent Cell Viability Assay is added, and the plate is read on a luminometer. Data are analyzed and plotted using GraphPad Prism software[1]. |
| Animal Admin | Mice: Mice bearing tumors are treated with ARV-771 (5, 10, 30, 50 mg/kg) for up to 3 wk, depending on the experiment. Mice are sacrificed 8 h after the final dose. Plasma and tissues are harvested and flash frozen for further analysis[1]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C49H60ClN9O7S2 |
| Molecular Weight | 986.640 |
| Exact Mass | 985.374573 |
| LogP | 3.84 |
| Index of Refraction | 1.674 |
| Storage condition | 2-8℃ |