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Your search keyword '"W. Seibel"' showing total 3 results
Start Over Author "W. Seibel" Publisher nature pub. group
3 results on '"W. Seibel"'

1. A novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration.

Author

Chen Y, Chen Y, Jastrzebska B, Golczak M, Gulati S, Tang H, Seibel W, Li X, Jin H, Han Y, Gao S, Zhang J, Liu X, Heidari-Torkabadi H, Stewart PL, Harte WE, Tochtrop GP, and Palczewski K

Subjects
ATP-Binding Cassette Transporters genetics, Alcohol Oxidoreductases genetics, Animals, Cell Line, Tumor, Disease Models, Animal, Diterpenes, Female, HEK293 Cells, High-Throughput Screening Assays, Humans, Light adverse effects, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, NIH 3T3 Cells, Neuroprotective Agents therapeutic use, Protein Transport drug effects, Protein Transport genetics, Retinal Degeneration etiology, Retinal Degeneration pathology, Retinal Rod Photoreceptor Cells metabolism, Retinal Rod Photoreceptor Cells pathology, Retinal Rod Photoreceptor Cells radiation effects, Retinaldehyde pharmacology, Retinaldehyde therapeutic use, Rhodopsin agonists, Rhodopsin antagonists & inhibitors, Rhodopsin genetics, Thiophenes therapeutic use, Treatment Outcome, Neuroprotective Agents pharmacology, Protein Folding drug effects, Retinal Degeneration drug therapy, Retinal Rod Photoreceptor Cells drug effects, Rhodopsin metabolism, Thiophenes pharmacology
Abstract

Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity. YC-001 binds to bovine rod opsin with an EC 50 similar to 9-cis-retinal. The chaperone activity of YC-001 is evidenced by its ability to rescue the transport of multiple rod opsin mutants in mammalian cells. YC-001 is also an inverse agonist that non-competitively antagonizes rod opsin signaling. Significantly, a single dose of YC-001 protects Abca4 -/- Rdh8 -/- mice from bright light-induced retinal degeneration, suggesting its broad therapeutic potential.

Published
2018
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2. Author Correction: Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia.

Author

Jiang X, Hu C, Ferchen K, Nie J, Cui X, Chen CH, Cheng L, Zuo Z, Seibel W, He C, Tang Y, Skibbe JR, Wunderlich M, Reinhold WC, Dong L, Shen C, Arnovitz S, Ulrich B, Lu J, Weng H, Su R, Huang H, Wang Y, Li C, Qin X, Mulloy JC, Zheng Y, Diao J, Jin J, Li C, Liu PP, He C, Chen Y, and Chen J

Abstract

The original version of this Article contained an error in the spelling of the author James C. Mulloy, which was incorrectly given as James Mulloy. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2018
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3. Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia.

Author

Jiang X, Hu C, Ferchen K, Nie J, Cui X, Chen CH, Cheng L, Zuo Z, Seibel W, He C, Tang Y, Skibbe JR, Wunderlich M, Reinhold WC, Dong L, Shen C, Arnovitz S, Ulrich B, Lu J, Weng H, Su R, Huang H, Wang Y, Li C, Qin X, Mulloy JC, Zheng Y, Diao J, Jin J, Li C, Liu PP, He C, Chen Y, and Chen J

Subjects
Animals, Antineoplastic Combined Chemotherapy Protocols pharmacology, Cell Line, Tumor, Daunorubicin administration & dosage, Enzyme Inhibitors administration & dosage, Gene Expression Regulation, Leukemic drug effects, Humans, Kaplan-Meier Estimate, Leukemia, Experimental drug therapy, Leukemia, Experimental genetics, Leukemia, Experimental metabolism, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute metabolism, Mice, Inbred C57BL, Mixed Function Oxygenases genetics, Mixed Function Oxygenases metabolism, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, RNA Interference, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, STAT5 Transcription Factor genetics, STAT5 Transcription Factor metabolism, THP-1 Cells, Enzyme Inhibitors pharmacology, Leukemia, Myeloid, Acute drug therapy, Mixed Function Oxygenases antagonists & inhibitors, Proto-Oncogene Proteins antagonists & inhibitors, STAT3 Transcription Factor antagonists & inhibitors, STAT5 Transcription Factor antagonists & inhibitors
Abstract

Effective therapy of acute myeloid leukemia (AML) remains an unmet need. DNA methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Through a series of data analysis and drug screening, we identified two compounds (i.e., NSC-311068 and NSC-370284) that selectively suppress TET1 transcription and 5-hydroxymethylcytosine (5hmC) modification, and effectively inhibit cell viability in AML with high expression of TET1 (i.e., TET1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8;21) AML. NSC-311068 and especially NSC-370284 significantly repressed TET1-high AML progression in vivo. UC-514321, a structural analog of NSC-370284, exhibited a more potent therapeutic effect and prolonged the median survival of TET1-high AML mice over three fold. NSC-370284 and UC-514321 both directly target STAT3/5, transcriptional activators of TET1, and thus repress TET1 expression. They also exhibit strong synergistic effects with standard chemotherapy. Our results highlight the therapeutic potential of targeting the STAT/TET1 axis by selective inhibitors in AML treatment.

Published
2017
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