AIM: To discover novel [20(OH)D3] analogs as antiproliferative therapeutics. MATERIALS AND METHODS: We studied in vitro liver microsome stability, in vivo toxicity using mice, vitamin D receptor (VDR) translocation, in vitro antiproliferative effect, CYP enzyme metabolism. RESULTS: 20S- and 20R(OH)D3 had reasonable half-lives of 50 min and 30 min (average) respectively in liver microsomes. They were non-hypercalcemic at a high dose of 60 μg/kg. Three new 20(OH)D3 analogs were designed, synthesized and tested. They showed higher or comparable potency for inhibition of proliferation of normal keratinocytes and in the induction of VDR translocation from cytoplasm to nucleus, compared to 1,25(OH)2D3. These new analogs demonstrated different degrees of metabolism through a range of vitamin D-metabolizing CYP enzymes. CONCLUSION: Their lack of calcemic toxicity at high doses and their high biological activity suggest that this novel 20(OH)D3 scaffold may represent a promising platform for further development of therapeutically-useful agents.
AIM: To discover novel [20(OH)D3] analogs as antiproliferative therapeutics. MATERIALS AND METHODS: We studied in vitro liver microsome stability, in vivo toxicity using mice, vitamin D receptor (VDR) translocation, in vitro antiproliferative effect, CYP enzyme metabolism. RESULTS: 20S- and 20R(OH)D3 had reasonable half-lives of 50 min and 30 min (average) respectively in liver microsomes. They were non-hypercalcemic at a high dose of 60 μg/kg. Three new 20(OH)D3 analogs were designed, synthesized and tested. They showed higher or comparable potency for inhibition of proliferation of normal keratinocytes and in the induction of VDR translocation from cytoplasm to nucleus, compared to 1,25(OH)2D3. These new analogs demonstrated different degrees of metabolism through a range of vitamin D-metabolizing CYP enzymes. CONCLUSION: Their lack of calcemic toxicity at high doses and their high biological activity suggest that this novel 20(OH)D3 scaffold may represent a promising platform for further development of therapeutically-useful agents.
Authors: Andrzej T Slominski; Wei Li; Syamal K Bhattacharya; Richard A Smith; Patti L Johnson; Jianjun Chen; Kathleen E Nelson; Robert C Tuckey; Duane Miller; Yan Jiao; Weikuan Gu; Arnold E Postlethwaite Journal: J Invest Dermatol Date: 2011-01-13 Impact factor: 8.551
Authors: Tae-Kang Kim; Jin Wang; Zorica Janjetovic; Jianjun Chen; Robert C Tuckey; Minh N Nguyen; Edith K Y Tang; Duane Miller; Wei Li; Andrzej T Slominski Journal: Mol Cell Endocrinol Date: 2012-04-21 Impact factor: 4.102
Authors: Andrzej Slominski; Jordan Zjawiony; Jacobo Wortsman; Igor Semak; Jeremy Stewart; Alexander Pisarchik; Trevor Sweatman; Josep Marcos; Chuck Dunbar; Robert C Tuckey Journal: Eur J Biochem Date: 2004-11
Authors: Edith K Y Tang; Jianjun Chen; Zorica Janjetovic; Elaine W Tieu; Andrzej T Slominski; Wei Li; Robert C Tuckey Journal: Drug Metab Dispos Date: 2013-03-01 Impact factor: 3.922
Authors: Andrzej T Slominski; Zorica Janjetovic; Brian E Fuller; Michal A Zmijewski; Robert C Tuckey; Minh N Nguyen; Trevor Sweatman; Wei Li; Jordan Zjawiony; Duane Miller; Tai C Chen; Gerard Lozanski; Michael F Holick Journal: PLoS One Date: 2010-03-26 Impact factor: 3.240
Authors: Robert C Tuckey; Wei Li; Jordan K Zjawiony; Michal A Zmijewski; Minh N Nguyen; Trevor Sweatman; Duane Miller; Andrzej Slominski Journal: FEBS J Date: 2008-04-10 Impact factor: 5.542
Authors: Michal A Zmijewski; Wei Li; Jordan K Zjawiony; Trevor W Sweatman; Jianjun Chen; Duane D Miller; Andrzej T Slominski Journal: Photochem Photobiol Sci Date: 2008-09-04 Impact factor: 3.982
Authors: Zorica Janjetovic; Michal A Zmijewski; Robert C Tuckey; Damon A DeLeon; Minh N Nguyen; Lawrence M Pfeffer; Andrzej T Slominski Journal: PLoS One Date: 2009-06-19 Impact factor: 3.240
Authors: Andrzej T Slominski; Michal A Zmijewski; Igor Semak; Trevor Sweatman; Zorica Janjetovic; Wei Li; Jordan K Zjawiony; Robert C Tuckey Journal: PLoS One Date: 2009-02-03 Impact factor: 3.240
Authors: Andrzej T Slominski; Anna A Brożyna; Michal A Zmijewski; Wojciech Jóźwicki; Anton M Jetten; Rebecca S Mason; Robert C Tuckey; Craig A Elmets Journal: Lab Invest Date: 2017-02-20 Impact factor: 5.662
Authors: Andrzej T Slominski; Anyamanee Chaiprasongsuk; Zorica Janjetovic; Tae-Kang Kim; Joanna Stefan; Radomir M Slominski; Vidya Sagar Hanumanthu; Chander Raman; Shariq Qayyum; Yuwei Song; Yuhua Song; Uraiwan Panich; David K Crossman; Mohammad Athar; Michael F Holick; Anton M Jetten; Michal A Zmijewski; Jaroslaw Zmijewski; Robert C Tuckey Journal: Cell Biochem Biophys Date: 2020-05-22 Impact factor: 2.194
Authors: Andrzej T Slominski; Tae-Kang Kim; Judith V Hobrath; Allen S W Oak; Edith K Y Tang; Elaine W Tieu; Wei Li; Robert C Tuckey; Anton M Jetten Journal: J Steroid Biochem Mol Biol Date: 2016-09-28 Impact factor: 4.292
Authors: Justyna M Wierzbicka; Michał A Żmijewski; Anna Piotrowska; Boguslaw Nedoszytko; Magdalena Lange; Robert C Tuckey; Andrzej T Slominski Journal: Mol Cell Endocrinol Date: 2016-08-12 Impact factor: 4.102
Authors: Zongtao Lin; Srinivasa R Marepally; Tae-Kang Kim; Zorica Janjetovic; Allen Sw Oak; Arnold E Postlethwaite; Linda K Myers; Robert C Tuckey; Andrzej T Slominski; Duane D Miller; Wei Li Journal: Anticancer Res Date: 2016-03 Impact factor: 2.480
Authors: Andrzej T Slominski; Anna A Brożyna; Michal A Zmijewski; Zorica Janjetovic; Tae-Kang Kim; Radomir M Slominski; Robert C Tuckey; Rebecca S Mason; Anton M Jetten; Purushotham Guroji; Jörg Reichrath; Craig Elmets; Mohammad Athar Journal: Adv Exp Med Biol Date: 2020 Impact factor: 2.622