Summary: Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.

Top Publications

  1. Sanford M, Scott L. Rotigotine transdermal patch: a review of its use in the treatment of Parkinson's disease. CNS Drugs. 2011;25:699-719 pubmed publisher
  2. Cummings S, Ensrud K, Delmas P, LaCroix A, Vukicevic S, Reid D, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med. 2010;362:686-96 pubmed publisher
    ..ClinicalTrials.gov number, NCT00141323.) ..
  3. Wullner U, Kassubek J, Odin P, Schwarz M, Naumann M, Häck H, et al. Transdermal rotigotine for the perioperative management of Parkinson's disease. J Neural Transm (Vienna). 2010;117:855-9 pubmed publisher
    ..Rotigotine treatment was considered feasible by patients, their anesthesiologists and neurologists with good control of PD symptoms and easy switching and re-switching of PD medication. ..
  4. Ensrud K, LaCroix A, Thompson J, Thompson D, Eastell R, Reid D, et al. Lasofoxifene and cardiovascular events in postmenopausal women with osteoporosis: Five-year results from the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL) trial. Circulation. 2010;122:1716-24 pubmed publisher
    ..5 mg/d was due primarily to lower risks of coronary revascularization procedures, hospitalization for unstable angina, and diagnosis of new ischemic heart disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00141323. ..
  5. Ratnam K, Feng X, Chuang P, Verma V, Lu T, Wang J, et al. Role of the retinoic acid receptor-? in HIV-associated nephropathy. Kidney Int. 2011;79:624-634 pubmed publisher
    ..Thus, a defect in the endogenous synthesis of retinoic acid contributes to loss of the protection by retinoic acid in HIVAN. Hence, RAR? agonists may be potential agents for the treatment of HIVAN. ..
  6. Nishimori H, Maeda Y, Teshima T, Sugiyama H, Kobayashi K, Yamasuji Y, et al. Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17. Blood. 2012;119:285-95 pubmed publisher
    ..These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD. ..
  7. Elshoff J, Braun M, Andreas J, Middle M, Cawello W. Steady-state plasma concentration profile of transdermal rotigotine: an integrated analysis of three, open-label, randomized, phase I multiple dose studies. Clin Ther. 2012;34:966-78 pubmed publisher
    ..Doses were achieved either by application of 1 large patch or a combination of smaller patches, resulting in the same total surface area. ..
  8. Sanz M, Albertos F, Otero E, Juez M, Morcillo E, Piqueras L. Retinoid X receptor agonists impair arterial mononuclear cell recruitment through peroxisome proliferator-activated receptor-? activation. J Immunol. 2012;189:411-24 pubmed publisher
    ..Thus, RXR agonists may constitute a new therapeutic tool in the control of the inflammatory process associated with cardiovascular disease. ..
  9. García L, Rivas Marín E, Floriano B, Bernhardt R, Ewen K, Reyes Ramírez F, et al. ThnY is a ferredoxin reductase-like iron-sulfur flavoprotein that has evolved to function as a regulator of tetralin biodegradation gene expression. J Biol Chem. 2011;286:1709-18 pubmed publisher

More Information


  1. Veeraraghavalu K, Zhang C, Miller S, Hefendehl J, Rajapaksha T, ULRICH J, et al. Comment on "ApoE-directed therapeutics rapidly clear ?-amyloid and reverse deficits in AD mouse models". Science. 2013;340:924-f pubmed publisher
    ..We now report that, although bexarotene reduces soluble A?40 levels in one of the mouse models, the drug has no impact on plaque burden in three strains that exhibit A? amyloidosis. ..
  2. Wei P, Walls M, Qiu M, Ding R, Denlinger R, Wong A, et al. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther. 2010;9:1618-28 pubmed publisher
    ..This compound is being investigated for the treatment of T-ALL and advanced solid tumors in phase I clinical trials. ..
  3. Tesseur I, Lo A, Roberfroid A, Dietvorst S, Van Broeck B, Borgers M, et al. Comment on "ApoE-directed therapeutics rapidly clear ?-amyloid and reverse deficits in AD mouse models". Science. 2013;340:924-e pubmed publisher
    ..We were not able to reproduce the described effects in several animal models. Drug formulation appears very critical. Our data call for extreme caution when considering this compound for use in AD patients. ..
  4. Boroojerdi B, Wolff H, Braun M, Scheller D. Rotigotine transdermal patch for the treatment of Parkinson's disease and restless legs syndrome. Drugs Today (Barc). 2010;46:483-505 pubmed publisher
    ..Overall, rotigotine transdermal patch has demonstrated favorable clinical efficacy and tolerability in the treatment of PD and RLS. ..
  5. Goldstein S, Neven P, Cummings S, Colgan T, Runowicz C, Krpan D, et al. Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause. 2011;18:17-22 pubmed publisher
    ..These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women. ..
  6. Price A, Xu G, Siemienski Z, Smithson L, Borchelt D, Golde T, et al. Comment on "ApoE-directed therapeutics rapidly clear ?-amyloid and reverse deficits in AD mouse models". Science. 2013;340:924-d pubmed publisher
    ..Using a nearly identical treatment regimen, we were unable to detect any evidence of drug efficacy despite demonstration of target engagement. ..
  7. Trenkwalder C, Kies B, Rudzinska M, Fine J, Nikl J, Honczarenko K, et al. Rotigotine effects on early morning motor function and sleep in Parkinson's disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord. 2011;26:90-9 pubmed publisher
    ..Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. ..
  8. Oertel W, Trenkwalder C, Benes H, Ferini Strambi L, Hogl B, Poewe W, et al. Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study. Lancet Neurol. 2011;10:710-20 pubmed publisher
    ..We did a prospective open-label extension of a 6-week, double-blind randomised trial to assess the safety, tolerability, and efficacy of rotigotine transdermal patch for up to 5 years in patients with restless legs syndrome...
  9. Cramer P, Cirrito J, Wesson D, Lee C, Karlo J, Zinn A, et al. ApoE-directed therapeutics rapidly clear ?-amyloid and reverse deficits in AD mouse models. Science. 2012;335:1503-6 pubmed publisher
    ..Thus, RXR activation stimulates physiological A? clearance mechanisms, resulting in the rapid reversal of a broad range of A?-induced deficits...
  10. Fitz N, Cronican A, Lefterov I, Koldamova R. Comment on "ApoE-directed therapeutics rapidly clear ?-amyloid and reverse deficits in AD mouse models". Science. 2013;340:924-c pubmed publisher
  11. Zhang C, Pavlicek A, Zhang Q, Lira M, Painter C, Yan Z, et al. Biomarker and pharmacologic evaluation of the ?-secretase inhibitor PF-03084014 in breast cancer models. Clin Cancer Res. 2012;18:5008-19 pubmed publisher
    ..The Notch pathway downstream genes may be used to predict the antitumor activity of PF-03084014 and enrich for responders among breast cancer patients. ..
  12. LaCroix A, Powles T, Osborne C, Wolter K, Thompson J, Thompson D, et al. Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women. J Natl Cancer Inst. 2010;102:1706-15 pubmed publisher
    ..78; 95% CI = 0.16 to 3.79; P(interaction) = .04). A 0.5-mg dose of lasofoxifene appears to reduce the risks of both total and ER+ invasive breast cancer in postmenopausal women with osteoporosis. ..
  13. Jarvis C, Goncalves M, Clarke E, Dogruel M, Kalindjian S, Thomas S, et al. Retinoic acid receptor-α signalling antagonizes both intracellular and extracellular amyloid-β production and prevents neuronal cell death caused by amyloid-β. Eur J Neurosci. 2010;32:1246-55 pubmed publisher
    ..In contrast, neither RARβ nor γ-agonists affect Aβ production or Aβ-mediated neuronal cell death. Therefore, RARα agonists have therapeutic potential for the treatment of AD. ..
  14. Ray Chaudhuri K, Martinez Martin P, Antonini A, Brown R, Friedman J, Onofrj M, et al. Rotigotine and specific non-motor symptoms of Parkinson's disease: post hoc analysis of RECOVER. Parkinsonism Relat Disord. 2013;19:660-5 pubmed publisher
    ..05). Rotigotine transdermal system may improve non-motor symptoms such as fatigue, symptoms of depression, anhedonia, and apathy in patients with PD; further prospective controlled studies are required to confirm this post hoc analysis. ..
  15. Dummer R, Beyer M, Hymes K, Epping M, Bernards R, Steinhoff M, et al. Vorinostat combined with bexarotene for treatment of cutaneous T-cell lymphoma: in vitro and phase I clinical evidence supporting augmentation of retinoic acid receptor/retinoid X receptor activation by histone deacetylase inhibition. Leuk Lymphoma. 2012;53:1501-8 pubmed publisher
    ..We conclude that concomitant administration of vorinostat and bexarotene is feasible only if lower doses of each drug are administered relative to the product label monotherapy doses. ..
  16. Schnitzler A, Leffers K, Häck H. High compliance with rotigotine transdermal patch in the treatment of idiopathic Parkinson's disease. Parkinsonism Relat Disord. 2010;16:513-6 pubmed publisher
    ..5%) were mostly mild or moderate in intensity. Rotigotine transdermal patch was associated with high compliance in patients with Parkinson's disease under clinical practice conditions. ..
  17. Duvic M, Dummer R, Becker J, Poulalhon N, Ortiz Romero P, Grazia Bernengo M, et al. Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer. 2013;49:386-94 pubmed publisher
    ..Despite a very conservative definition of disease progression, panobinostat demonstrated activity with a manageable safety profile in bexarotene-exposed and -naïve CTCL patients. ClinicalTrials.gov Identifier: NCT00425555. ..
  18. Oertel W, LeWitt P, Giladi N, Ghys L, Grieger F, Boroojerdi B. Treatment of patients with early and advanced Parkinson's disease with rotigotine transdermal system: age-relationship to safety and tolerability. Parkinsonism Relat Disord. 2013;19:37-42 pubmed publisher
    ..Data from more representative PD populations are required to fully assess potential risks of DA therapy in elderly patients. ..
  19. Abbott R, Whittaker S, Morris S, Russell Jones R, Hung T, Bashir S, et al. Bexarotene therapy for mycosis fungoides and Sézary syndrome. Br J Dermatol. 2009;160:1299-307 pubmed publisher
    ..Bexarotene (Targretin) is a synthetic retinoid which is licensed for the treatment of advanced refractory cutaneous T-cell lymphoma (CTCL)...
  20. Trenkwalder C, Benes H, Poewe W, Oertel W, Garcia Borreguero D, de Weerd A, et al. Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2008;7:595-604 pubmed publisher
    ..24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome. Schwarz Biosciences. ..
  21. Oertel W, Benes H, Garcia Borreguero D, Geisler P, Hogl B, Saletu B, et al. Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe. Sleep Med. 2008;9:228-39 pubmed
    ..This dose-finding trial identified the range for a maintenance dose of rotigotine from 1mg/24h to 3mg/24h. The lowest dose was ineffective and, with the highest dose, no additional benefit was observed. ..
  22. Potera C. The sweet scent on baby's breath?. Environ Health Perspect. 2007;115:A491 pubmed
  23. LeWitt P, Boroojerdi B, MacMahon D, Patton J, Jankovic J. Overnight switch from oral dopaminergic agonists to transdermal rotigotine patch in subjects with Parkinson disease. Clin Neuropharmacol. 2007;30:256-65 pubmed
    ..Subjects and clinicians found the overnight switch to rotigotine convenient, well tolerated, and effective for control of PD signs and symptoms for subjects previously receiving low-to-moderate doses of oral dopaminergic agonists. ..
  24. Tooker P, Yen W, Ng S, Negro Vilar A, Hermann T. Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification. Cancer Res. 2007;67:4425-33 pubmed
    ..This suggests that bexarotene may have clinical utility in cancers where drug resistance by gene amplification is a major obstacle to successful therapy. ..
  25. Yen W, Prudente R, Lamph W. Synergistic effect of a retinoid X receptor-selective ligand bexarotene (LGD1069, Targretin) and paclitaxel (Taxol) in mammary carcinoma. Breast Cancer Res Treat. 2004;88:141-8 pubmed
    ..In summary, our results demonstrated the potential of using a RXR selective ligand in combination with chemotherapy for the treatment of breast cancer. ..
  26. Schupp M, Curtin J, Kim R, Billin A, Lazar M. A widely used retinoic acid receptor antagonist induces peroxisome proliferator-activated receptor-gamma activity. Mol Pharmacol. 2007;71:1251-7 pubmed
    ..Ro 41-5253 is a PPARgamma agonist as well as an RARalpha antagonist whose pleiotropic effects on NRs may signify a unique spectrum of biological responses. ..
  27. Naidu Y, Chaudhuri K. Transdermal rotigotine: a new non-ergot dopamine agonist for the treatment of Parkinson's disease. Expert Opin Drug Deliv. 2007;4:111-8 pubmed
    ..Clinical trials demonstrate the efficacy of rotigotine in early and advanced Parkinson's disease, with important implications for treatment of non-motor symptoms of Parkinson's disease. ..
  28. Martínez Pérez O, López Sánchez A, Reyes Ramírez F, Floriano B, Santero E. Integrated response to inducers by communication between a catabolic pathway and its regulatory system. J Bacteriol. 2007;189:3768-75 pubmed
  29. Ashby R, McCarthy C, Maleszka R, Megaw P, Morgan I. A muscarinic cholinergic antagonist and a dopamine agonist rapidly increase ZENK mRNA expression in the form-deprived chicken retina. Exp Eye Res. 2007;85:15-22 pubmed
    ..These results suggest that both muscarinic acetylcholine antagonists and dopamine agonists act early in the signal cascade controlling eye growth, possibly within the retina itself. ..
  30. Ke H, Foley G, Simmons H, Shen V, Thompson D. Long-term treatment of lasofoxifene preserves bone mass and bone strength and does not adversely affect the uterus in ovariectomized rats. Endocrinology. 2004;145:1996-2005 pubmed
    ..These data suggest that lasofoxifene is an effective antiosteoporosis agent, and its efficacy and safety can be maintained over an extended period of time. ..
  31. Hoover L, Burton E, O Neill M, Brooks B, Sreedharan S, Dawson N, et al. Retinoids regulate TGFbeta signaling at the level of Smad2 phosphorylation and nuclear accumulation. Biochim Biophys Acta. 2008;1783:2279-86 pubmed publisher
    ..These data show retinoid signaling influences the TGFbeta pathway in an acute and direct manner that has been unappreciated until now. ..
  32. Watts R, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology. 2007;68:272-6 pubmed
    ..Adverse events were similar to those found with other transdermal systems and dopamine agonists. ..
  33. Martínez Pérez O, Moreno Ruiz E, Floriano B, Santero E. Regulation of tetralin biodegradation and identification of genes essential for expression of thn operons. J Bacteriol. 2004;186:6101-9 pubmed
  34. Stiasny Kolster K, Kohnen R, Schollmayer E, Moller J, Oertel W. Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord. 2004;19:1432-8 pubmed
    ..This pilot study suggests that continuous delivery of rotigotine by means of a patch may provide an effective and well-tolerated treatment of RLS symptoms both during night and day. ..
  35. Giladi N, Boroojerdi B, Korczyn A, Burn D, Clarke C, Schapira A. Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord. 2007;22:2398-404 pubmed
    ..Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease. ..
  36. Li Y, Zhang Y, Hill J, Shen Q, Kim H, Xu X, et al. The Rexinoid LG100268 prevents the development of preinvasive and invasive estrogen receptor negative tumors in MMTV-erbB2 mice. Clin Cancer Res. 2007;13:6224-31 pubmed
    ..Rexinoid LG100268 is an effective chemopreventive agent in preventing the development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice. ..
  37. Pinkerton J, Goldstein S. Endometrial safety: a key hurdle for selective estrogen receptor modulators in development. Menopause. 2010;17:642-53 pubmed publisher
    ..Further investigation of newer SERMs is warranted to more clearly define the endometrial safety of these agents. ..
  38. LeWitt P, Lyons K, Pahwa R. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology. 2007;68:1262-7 pubmed
  39. Moreno Ruiz E, Hernáez M, Martínez Pérez O, Santero E. Identification and functional characterization of Sphingomonas macrogolitabida strain TFA genes involved in the first two steps of the tetralin catabolic pathway. J Bacteriol. 2003;185:2026-30 pubmed
    ..ThnA1, ThnA2, and ThnA3 were essential for tetralin ring-hydroxylating dioxygenase activity. ThnB was identified as a dehydrogenase required for tetralin biodegradation. ..
  40. Fu J, Ding Y, Huang D, Li H, Chen X. The retinoid X receptor-selective ligand, LGD1069, inhibits tumor-induced angiogenesis via suppression of VEGF in human non-small cell lung cancer. Cancer Lett. 2007;248:153-63 pubmed
    ..Collectively, our results suggest a role of LGD1069 in treatment for non-small cell lung cancer by inhibition of tumor-induced angiogenesis. ..
  41. Cesario R, Stone J, Yen W, Bissonnette R, Lamph W. Differentiation and growth inhibition mediated via the RXR:PPARgamma heterodimer in colon cancer. Cancer Lett. 2006;240:225-33 pubmed
    ..These findings were confirmed in vivo in a Moser xenograft tumor model. Collectively, our data suggest a potential role for utilizing a combination regimen of a RXR and PPARgamma agonist in the treatment of colon cancer. ..
  42. Yen W, Lamph W. The selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced breast carcinoma. Mol Cancer Ther. 2005;4:824-34 pubmed
    ..Our results suggest a role for bexarotene in combination with chemotherapeutic agents in prevention and overcoming acquired drug resistance in advanced breast carcinoma. ..
  43. Esteva F, Glaspy J, Baidas S, Laufman L, Hutchins L, Dickler M, et al. Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer. J Clin Oncol. 2003;21:999-1006 pubmed
    ..However, it is an oral agent with minimal toxicity and a unique mechanism of action, which produced clinical benefit in approximately 20% of patients. Future efforts should define populations likely to benefit from this agent. ..
  44. Castner S, Goldman Rakic P. Enhancement of working memory in aged monkeys by a sensitizing regimen of dopamine D1 receptor stimulation. J Neurosci. 2004;24:1446-50 pubmed
  45. Yen W, Corpuz M, Prudente R, Cooke T, Bissonnette R, Negro Vilar A, et al. A selective retinoid X receptor agonist bexarotene (Targretin) prevents and overcomes acquired paclitaxel (Taxol) resistance in human non-small cell lung cancer. Clin Cancer Res. 2004;10:8656-64 pubmed
    ..Our results suggest that bexarotene may offer a novel approach to prevent and overcome paclitaxel resistance in patients with NSCLC. ..
  46. Yen W, Lamph W. A selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced prostate cancer. Prostate. 2006;66:305-16 pubmed
    ..Our results suggest a role of bexarotene in combination with chemotherapeutic agents in prevention and overcoming acquired drug resistance in advanced prostate cancer. ..
  47. Rasooly R, Schuster G, Gregg J, Xiao J, Chandraratna R, Stephensen C. Retinoid x receptor agonists increase bcl2a1 expression and decrease apoptosis of naive T lymphocytes. J Immunol. 2005;175:7916-29 pubmed
    ..Thus, this effect on Bcl2a1 expression may account for the decreased apoptosis seen in naive T lymphocytes treated with RXR agonists. ..
  48. Fountaine R, Nishizawa Y, Wei G, Dogolo L, Calcagni A, Gardner M. Clinical pharmacology of lasofoxifene in Japanese and white postmenopausal women. J Clin Pharmacol. 2006;46:693-9 pubmed
  49. Folkertsma S, van Noort P, de Heer A, Carati P, Brandt R, Visser A, et al. The use of in vitro peptide binding profiles and in silico ligand-receptor interaction profiles to describe ligand-induced conformations of the retinoid X receptor alpha ligand-binding domain. Mol Endocrinol. 2007;21:30-48 pubmed
  50. Klemann C, Raveney B, Klemann A, Ozawa T, von Horsten S, Shudo K, et al. Synthetic retinoid AM80 inhibits Th17 cells and ameliorates experimental autoimmune encephalomyelitis. Am J Pathol. 2009;174:2234-45 pubmed publisher
    ..These findings suggest that retinoid signaling regulates both inflammatory Th17 cells and Th17-like regulatory cells. ..
  51. Rascol O, Perez Lloret S. Rotigotine transdermal delivery for the treatment of Parkinson's disease. Expert Opin Pharmacother. 2009;10:677-91 pubmed
  52. Oertel W, Benes H, Garcia Borreguero D, Geisler P, Hogl B, Trenkwalder C, et al. One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome. Sleep Med. 2008;9:865-73 pubmed publisher
    ..The transdermal patch was safe and generally well tolerated by the majority of patients. Comparable to any transdermal therapy, application site reactions were the main treatment complication. ..
  53. Gardner M, Taylor A, Wei G, Calcagni A, Duncan B, Milton A. Clinical pharmacology of multiple doses of lasofoxifene in postmenopausal women. J Clin Pharmacol. 2006;46:52-8 pubmed
    ..09 ng/mL to 6.43 ng/mL. Lasofoxifene partially suppressed luteinizing hormone, follicle-stimulating hormone, low-density lipoprotein, and N-telopeptide. ..