High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor
High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor
Prostate cancer is the most frequently diagnosed malignancy in men. growth is primarily dependent on the activity of the androgen receptor (AR), justifies the use of androgen deficiency therapy as a standard treatment for metastatic disease. Inhibition of androgen antagonists axis using the second generation have improved patient survival, yet are systematically exposed to the mechanisms of resistance, which leads to an average life not exceeding 5 years.
Counteracting this opposition has become the object of a large number of investigations, with particular emphasis on the identification of new AR inhibitors, whether they are hostile to the receptor by competitive or non-competitive binding. To this end, a lot of high content screens have been done, to identify non-steroidal AR antagonists new, using a variety of approaches, but reported the results somewhat controversial, depending on the approach and the model cells used for screening. In our study, we used U2OS osteosarcoma cells stably transfected with AR or ARv7 and luciferase reporter as the previous model validated to screen libraries of phytochemical Prestwick.
The results of our screen identified ellipticine, harmol and harmine hydrochloride as a hit was confirmed. Surprisingly, we could show that harmol hydrochloride, previously identified as inhibitors of non-competitive AR or inhibitor weak signal androgen, the actual competitive antagonist of the AR, which inhibit the growth line of prostate cancer VCAP, the concentration of which does not affect the growth of DU145 and PC3 cells AR negative , Interestingly, we also reported for the first time that harmol hydrochloride is selective for the AR, because it can not alter the activity of other nuclear receptors, such as the glucocorticoid receptor (GR), progesterone receptor (PR), or mineralocorticoid receptor (MR).
In addition, we show that, contrary to enzalutamide, harmol hydrochloride showed no athletic activity against pregnane X receptor (PXR), a master regulator of drug metabolism. Together, our results explain the importance of the cellular context to playback new AR antagonists. They further indicated that several potential hits were identified previously may have been overlooked.
High Content Screening Using New U2OS Reporter Cell Models Identifies Harmol Hydrochloride as a Selective and Competitive Antagonist of the Androgen Receptor
high content drug screening for Fanconi anemia therapy
ackground: Fanconi anemia is a rare disease clinically characterized by malformations, bone marrow failure and an increased risk of solid tumors and hematologic malignancies. The only treatment available is hematopoietic stem cell transplantation for bone marrow failure or leukemia, and surgical resection of solid tumors. Therefore, there is still an urgent need for new therapeutic options. With this purpose, we developed a cell-based high-content screening assays to identify new drugs with therapeutic potential in FA.
Results: A line U2OS cell-mediated talen FANCA-deficient were stably transfected with YFP-fusion protein FANCD2. These cells can not form the focus of fluorescent or monoubiquitinate endogenous or exogenous FANCD2 to DNA damage and is more sensitive to mitomycin C when compared to the parental wild-type counterparts. FANCA correction by retroviral infection restored the ability of the cell lines to form FANCD2 focus and ubiquitinate FANCD2.
Feasibility of cell-based system is interrogated in utero screening of 3802 compounds, including Prestwick library 1200 FDA-approved drugs. Potential Hits individually identified and then tested for their ability to save FANCD2 focus and monoubiquitination and chromosome stability in the absence of FANCA.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rabbit Angiotensin I Converting Enzyme (ACE) in serum, plasma and other biological fluids.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rabbit Angiotensin I Converting Enzyme (ACE) in serum, plasma and other biological fluids.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rabbit Angiotensin I Converting Enzyme (ACE) in serum, plasma and other biological fluids.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rabbit Angiotensin I Converting Enzyme (ACE) in serum, plasma and other biological fluids.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Rabbit Angiotensin I Converting Enzyme (ACE) in samples from Serum, plasma and other biological fluids. with no significant corss-reactivity with analogues from other species.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rabbit Angiotensin I Converting Enzyme (ACE) in samples from serum, plasma or other biological fluids.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rabbit Angiotensin I Converting Enzyme (ACE) in samples from serum, plasma or other biological fluids.
Rabbit Angiotensin I Converting Enzyme (ACE) ELISA Kit
Description: A sandwich ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Mouse Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Mouse Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Mouse Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Porcine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Porcine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Porcine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Monkey Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Monkey Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Monkey Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Goat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Goat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Goat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Canine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Canine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Canine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Angiotensin I Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive for quantitative measurement of Rabbit Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive for quantitative measurement of Rabbit Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive for quantitative measurement of Rabbit Angiotensin Converting Enzyme in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Rabbit Angiotensin I Converting Enzyme 2 (ACE2) ELISA Kit
Description: A sandwich ELISA kit for detection of Angiotensin I Converting Enzyme from Rabbit in samples from blood, serum, plasma, cell culture fluid and other biological fluids.
ACE ELISA Kit| Rabbit Angiotensin I Converting Enzyme ELISA Kit
Conclusion: While, unfortunately, there is no tested compounds were able to restore FANCA-deficient cell, our studies show the potential capacity to screen large compound libraries in the context of Fanconi anemia therapy on optimized and cost-effective platform.
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