tetrahydroisoquinolines

Summary

Summary: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.

Top Publications

  1. D INCALCI M, Galmarini C. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010;9:2157-63 pubmed publisher
    ..One of these combinations (trabectedin-pegylated liposomal doxorubicin) was recently authorized by the European Commission for the treatment of patients with relapsed platinum-sensitive ovarian cancer. ..
  2. Wu H, Wacker D, Mileni M, KATRITCH V, Han G, Vardy E, et al. Structure of the human ?-opioid receptor in complex with JDTic. Nature. 2012;485:327-32 pubmed publisher
  3. Grosso F, D INCALCI M, Cartoafa M, Nieto A, Fernández Teruel C, Alfaro V, et al. A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin. Cancer Chemother Pharmacol. 2012;69:1557-65 pubmed publisher
    ..This analysis determined the incidence of serious rhabdomyolysis events reported during trabectedin treatment since the first phase I clinical trial in April 1996 up to September 2010...
  4. Wang S, Onaran M, Seto C. Enantioselective synthesis of 1-aryltetrahydroisoquinolines. Org Lett. 2010;12:2690-3 pubmed publisher
    ..Pinacol arylboronic esters are the optimal precursors for the arylzinc reagents. This method is applied to the enantioselective synthesis of Solifenacin. ..
  5. Le Cesne A, Yovine A, Blay J, Delaloge S, Maki R, Misset J, et al. A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials. Invest New Drugs. 2012;30:1193-202 pubmed publisher
    ..Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time. ..
  6. Xu G, Yan Z, Wang N, Liu Z. Synthesis and cytotoxicity of cis-dichloroplatinum (II) complexes of (1S,3S)-1,2,3,4-tetrahydroisoquinolines. Eur J Med Chem. 2011;46:356-63 pubmed publisher
    A series of novel cisplatin-type platinum complexes with (1S,3S)-1,2,3,4-tetrahydroisoquinolines as the ligands were synthesized as potential anticancer agents in several steps starting from commercially available l-DOPA...
  7. Leal J, Martinez Diez M, García Hernández V, Moneo V, Domingo A, Bueren Calabuig J, et al. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. Br J Pharmacol. 2010;161:1099-110 pubmed publisher
    ..The potent anti-tumour activity of PM01183 in several murine models of human cancer supports its development as a novel anti-neoplastic agent. ..
  8. Baruchel S, Pappo A, Krailo M, Baker K, Wu B, Villaluna D, et al. A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group. Eur J Cancer. 2012;48:579-85 pubmed publisher
    ..To determine the toxicity, efficacy and pharmacokinetics of trabectedin given over 24h every 3 weeks to children with recurrent rhabdomyosarcoma, Ewing sarcoma, or non-rhabdomyosarcoma soft tissue sarcomas...
  9. Schank J, Goldstein A, Rowe K, King C, Marusich J, Wiley J, et al. The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety. Addict Biol. 2012;17:634-47 pubmed publisher
    ..Our results provide additional evidence for the involvement of KOR in regulation of alcohol-related behaviors and provide support for KOR antagonists, including JDTic, to be evaluated as medications for alcoholism. ..

More Information

Publications62

  1. Munro T, Berry L, Van t Veer A, Beguin C, Carroll F, Zhao Z, et al. Long-acting ? opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity. BMC Pharmacol. 2012;12:5 pubmed publisher
    ..We propose that this persistence may result from entrapment in cellular compartments such as lysosomes. ..
  2. Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23:249-62 pubmed publisher
    ..This unexpected property may be exploited in different therapeutic strategies. ..
  3. Paz Ares L, Lopez Pousa A, Poveda A, Balañá C, Ciruelos E, Bellmunt J, et al. Trabectedin in pre-treated patients with advanced or metastatic soft tissue sarcoma: a phase II study evaluating co-treatment with dexamethasone. Invest New Drugs. 2012;30:729-40 pubmed publisher
    ..Trabectedin has confirmed activity in patients with pretreated STS. This study shows that co-treatment with dexamethasone improves the safety of trabectedin by reducing drug-induced hepatotoxicity and myelosuppression. ..
  4. Feng S, Jiang J, Hu P, Zhang J, Liu T, Zhao Q, et al. A phase I study on pharmacokinetics and pharmacodynamics of higenamine in healthy Chinese subjects. Acta Pharmacol Sin. 2012;33:1353-8 pubmed publisher
    ..1 ?g/L, respectively. Higenamine has desirable pharmacokinetic and pharmacodynamic characteristics. The results provide important information for future clinical studies on higenamine. ..
  5. Samuels B, Chawla S, Patel S, von Mehren M, Hamm J, Kaiser P, et al. Clinical outcomes and safety with trabectedin therapy in patients with advanced soft tissue sarcomas following failure of prior chemotherapy: results of a worldwide expanded access program study. Ann Oncol. 2013;24:1703-9 pubmed publisher
    ..clinicaltrials.gov: nct00210665. ..
  6. Su W, Yu J, Li Z, Jiang Z. Solvent-free cross-dehydrogenative coupling reactions under high speed ball-milling conditions applied to the synthesis of functionalized tetrahydroisoquinolines. J Org Chem. 2011;76:9144-50 pubmed publisher
    ..ball milling technique has been first applied to cross-dehydrogenative coupling (CDC) reactions between tetrahydroisoquinolines and three types of pronucleophiles such as nitroalkanes, alkynes, and indoles...
  7. Antkiewicz Michaluk L, Wasik A, Romańska I, Bojarski A, Michaluk J. Both stereoselective (R)- and (S)-1-Methyl-1,2,3,4-tetrahydroisoquinoline enantiomers protect striatal terminals against rotenone-induced suppression of dopamine release. Neurotox Res. 2011;20:134-49 pubmed publisher
  8. Kuszczyk M, Słomka M, Antkiewicz Michaluk L, Salinska E, Łazarewicz J. 1-Methyl-1,2,3,4-tetrahydroisoquinoline and established uncompetitive NMDA receptor antagonists induce tolerance to excitotoxicity. Pharmacol Rep. 2010;62:1041-50 pubmed
    ..Moreover, our data disclose a new mechanism of 1MeTIQ-evoked neuroprotection based on the induction of neuronal tolerance to excitotoxicity. ..
  9. Monk B, Herzog T, Kaye S, Krasner C, Vermorken J, Muggia F, et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010;28:3107-14 pubmed publisher
  10. Zheng Q, Meng W, Jiang G, Yu Z. CuI-catalyzed C1-alkynylation of tetrahydroisoquinolines (THIQs) by A3 reaction with tunable iminium ions. Org Lett. 2013;15:5928-31 pubmed publisher
    A CuI-catalyzed A(3) (amines, aldehydes and alkynes) reaction of tetrahydroisoquinolines (THIQs), aldehydes, and alkynes to give C1-alkynylated THIQ products (endo-yne-THIQs) was developed...
  11. Watson A, Soro Paavonen A, Sheehy K, Li J, Calkin A, Koitka A, et al. Delayed intervention with AGE inhibitors attenuates the progression of diabetes-accelerated atherosclerosis in diabetic apolipoprotein E knockout mice. Diabetologia. 2011;54:681-9 pubmed publisher
    ..These findings provide further evidence that blockade of AGE-mediated pathways may present a novel therapy for the prevention of atherosclerosis in diabetes. ..
  12. Stoyianni A, Kapodistrias N, Kampletsas E, Pentheroudakis G, Pavlidis N. Trabectedin-related rhabdomyolysis: an uncommon but fatal toxicity. Tumori. 2011;97:252-5 pubmed publisher
  13. Wang S, Chai Z, Zhou S, Wang S, Zhu X, Wei Y. A novel Lewis acid catalyzed [3 + 3]-annulation strategy for the syntheses of tetrahydro-?-carbolines and tetrahydroisoquinolines. Org Lett. 2013;15:2628-31 pubmed publisher
    ..acid catalyzed [3 + 3]-annulation process for the efficient syntheses of both tetrahydro-?-carbolines and tetrahydroisoquinolines from readily available benzylic alcohols and aziridines was developed, which would be a highly valuable ..
  14. Martinez S, Perez L, Galmarini C, Aracil M, Tercero J, Gago F, et al. Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway. Br J Pharmacol. 2013;170:871-82 pubmed publisher
    ..These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of 'fanconizing' cancer cells in order to make them more sensitive to other anti-tumour drugs. ..
  15. Pérez Ruixo C, Valenzuela B, Fernández Teruel C, González Sales M, Miguel Lillo B, Soto Matos A, et al. Population pharmacokinetics of PM00104 (Zalypsis(®)) in cancer patients. Cancer Chemother Pharmacol. 2012;69:15-24 pubmed publisher
    ..No clinically relevant covariates were identified as predictors of PM00104 pharmacokinetics. ..
  16. Le Cesne A, Cresta S, Maki R, Blay J, Verweij J, Poveda A, et al. A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas. Eur J Cancer. 2012;48:3036-44 pubmed publisher
    ..Since these promising results were generally noted in patients following chemotherapy, a phase III randomised trial in first-line is ongoing to compare trabectedin with doxorubicin-based chemotherapy in patients with TRS. ..
  17. Schoffski P, Wolter P, Clement P, Sciot R, De Wever I, Wozniak A, et al. Trabectedin (ET-743): evaluation of its use in advanced soft-tissue sarcoma. Future Oncol. 2007;3:381-92 pubmed
    ..Trabectedin is an interesting new anticancer agent that offers much promise for the treatment of advanced soft-tissue sarcoma. ..
  18. Guirouilh Barbat J, Antony S, Pommier Y. Zalypsis (PM00104) is a potent inducer of gamma-H2AX foci and reveals the importance of the C ring of trabectedin for transcription-coupled repair inhibition. Mol Cancer Ther. 2009;8:2007-14 pubmed publisher
  19. Martinez N, Sanchez Beato M, Carnero A, Moneo V, Tercero J, Fernandez I, et al. Transcriptional signature of Ecteinascidin 743 (Yondelis, Trabectedin) in human sarcoma cells explanted from chemo-naive patients. Mol Cancer Ther. 2005;4:814-23 pubmed
    ..The transcriptional signature described here may lead to the identification of ET-743 downstream mediators and transcription regulators and the proposal of strategies by which ET-743-sensitive tumors may be identified. ..
  20. Luszczki J, Antkiewicz Michaluk L, Raszewski G, Czuczwar S. Interactions of 1-methyl-1,2,3,4-tetrahydroisoquinoline with lamotrigine, oxcarbazepine, pregabalin, and topiramate in the mouse maximal electroshock-induced seizure model: a type I isobolographic analysis. Epilepsy Res. 2010;89:207-19 pubmed publisher
    ..The combinations of MeTHIQ with LTG, OXC and PGB were neutral in the mouse MES model. ..
  21. Fayette J, Boyle H, Chabaud S, Favier B, Engel C, Cassier P, et al. Efficacy of trabectedin for advanced sarcomas in clinical trials versus compassionate use programs: analysis of 92 patients treated in a single institution. Anticancer Drugs. 2010;21:113-9 pubmed publisher
    ..The safety and tolerability of trabectedin shown in clinical trials is confirmed for patients in real-life situation treated in compassionate use programs, but its benefit is higher for patients with performance status 0-1. ..
  22. Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, Tavecchio M, et al. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther. 2009;8:449-57 pubmed publisher
    ..These data provide a rationale for the specific activity of trabectedin and open the perspective of combinatorial treatments with drugs acting on lipogenic pathways...
  23. Carter N, Keam S. Trabectedin : a review of its use in the management of soft tissue sarcoma and ovarian cancer. Drugs. 2007;67:2257-76 pubmed
  24. Fayette J, Coquard I, Alberti L, Boyle H, Meeus P, Decouvelaere A, et al. ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol. 2006;18:347-53 pubmed
    ..Phase I combination studies are in currently progress. ET-743 is a novel active drug for sarcoma which yields prolonged disease-free survival in subsets of patients. ..
  25. Cheng P, Huang N, Jiang Z, Zhang Q, Zheng Y, Chen J, et al. 1-Aryl-tetrahydroisoquinoline analogs as active anti-HIV agents in vitro. Bioorg Med Chem Lett. 2008;18:2475-8 pubmed publisher
    A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization...
  26. von Mehren M, Schilder R, Cheng J, Temmer E, Cardoso T, Renshaw F, et al. A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies. Ann Oncol. 2008;19:1802-9 pubmed publisher
    ..These results support the need for additional studies of this combination in appropriate cancer types. ..
  27. Kuo C, Wu M. The synthesis of N-phenoxyethyl-1-substituted-1,2,3,4-tetrahydroisoquinolines and their alpha1-adrenoceptor blocking activity. Eur J Med Chem. 2009;44:1271-7 pubmed publisher
    ..On the other hand, the electron-donating group at the 6-position of isoquinoline ring either increases or decreases the alpha(1)-adrenoceptor blocking activity. ..
  28. Wasik A, Romańska I, Antkiewicz Michaluk L. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous parkinsonism-inducing toxin, strongly potentiates MAO-dependent dopamine oxidation and impairs dopamine release: ex vivo and in vivo neurochemical studies. Neurotox Res. 2009;15:15-23 pubmed publisher
    ..Because 1BnTIQ is an endogenous compound, it may be one of the factors responsible for idiopathic Parkinson's disease. ..
  29. Leal J, García Hernández V, Moneo V, Domingo A, Bueren Calabuig J, Negri A, et al. Molecular pharmacology and antitumor activity of Zalypsis in several human cancer cell lines. Biochem Pharmacol. 2009;78:162-70 pubmed publisher
    ..Taken together, these results indicate that the potent antitumor activity of Zalypsis supports its current development in the clinic as an anticancer agent. ..
  30. McMeekin D, Lisyanskaya A, Crispens M, Oza A, Braly P, Doering D, et al. Single-agent trabectedin as second-line therapy of persistent or recurrent endometrial cancer: results of a multicenter phase II study. Gynecol Oncol. 2009;114:288-92 pubmed publisher
    ..Single-agent trabectedin displayed minimal antitumor activity in this pretreated population of women with persistent or recurrent endometrial cancer. ..
  31. Antkiewicz Michaluk L, Lazarewicz J, Patsenka A, Kajta M, Zieminska E, Salinska E, et al. The mechanism of 1,2,3,4-tetrahydroisoquinolines neuroprotection: the importance of free radicals scavenging properties and inhibition of glutamate-induced excitotoxicity. J Neurochem. 2006;97:846-56 pubmed
    1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), unlike several other tetrahydroisoquinolines, displays neuroprotective properties...
  32. Krasner C, McMeekin D, Chan S, Braly P, Renshaw F, Kaye S, et al. A Phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007;97:1618-24 pubmed
    ..Trabectedin is an active treatment, with documented responses in patients with platinum sensitive advanced relapsed ovarian cancer, and has a manageable toxicity profile. ..
  33. Ludwig M, Hoesl C, Höfner G, Wanner K. Affinity of 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives to the ion channel binding site of the NMDA receptor complex. Eur J Med Chem. 2006;41:1003-10 pubmed
    ..Additionally, a convenient and efficient synthetic approach to racemic 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives is described. ..
  34. Park J, Kang Y, Park M, Lee Y, Kim H, Seo H, et al. Enantiomers of higenamine inhibit LPS-induced iNOS in a macrophage cell line and improve the survival of mice with experimental endotoxemia. Int Immunopharmacol. 2006;6:226-33 pubmed
    ..Taken together, it was concluded that (S)-higenamine may be more beneficial than (R)-enantiomer in diseases associated with iNOS over-expression, such as septic shock. ..
  35. Lorenc Koci E, Gołembiowska K, Wardas J. 1,2,3,4-Tetrahydroisoquinoline protects terminals of dopaminergic neurons in the striatum against the malonate-induced neurotoxicity. Brain Res. 2005;1051:145-54 pubmed
  36. Herrero A, Martín Castellanos C, Marco E, Gago F, Moreno S. Cross-talk between nucleotide excision and homologous recombination DNA repair pathways in the mechanism of action of antitumor trabectedin. Cancer Res. 2006;66:8155-62 pubmed
    ..These results lead us to propose a model for the action of trabectedin in eukaryotic cells in which the formation of a Rad13/DNA-trabectedin ternary complex, stabilized by Arg961, results in cell death. ..
  37. Fetterly G, Owen J, Stuyckens K, Passarell J, Zannikos P, Soto Matos A, et al. Semimechanistic pharmacokinetic/pharmacodynamic model for hepatoprotective effect of dexamethasone on transient transaminitis after trabectedin (ET-743) treatment. Cancer Chemother Pharmacol. 2008;62:135-47 pubmed
    ..The model predicts that co-administration of dexamethasone and the suggested dose reduction strategy based on the serum concentration of liver enzymes will enhance the safe use of trabectedin in the clinic. ..
  38. Allavena P, Signorelli M, Chieppa M, Erba E, Bianchi G, Marchesi F, et al. Anti-inflammatory properties of the novel antitumor agent yondelis (trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res. 2005;65:2964-71 pubmed
  39. Sun J, Kim H, Seo H, Lee J, Yun Choi H, Chang K. YS 49, 1-(alpha-naphtylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, regulates angiotensin II-stimulated ROS production, JNK phosphorylation and vascular smooth muscle cell proliferation via the induction of heme oxygenase-1. Life Sci. 2008;82:600-7 pubmed publisher
    ..Therefore, YS 49 has potential as a therapeutic strategy for the pathogenesis of Ang II-related vascular diseases such as hypertension and atherosclerosis, via the induction of HO-1 gene activity. ..
  40. Beumer J, Lopez Lazaro L, Schellens J, Beijnen J, van Tellingen O. Evaluation of human plasma protein binding of trabectedin (Yondelis, ET-743). Curr Clin Pharmacol. 2009;4:38-42 pubmed
    ..We can conclude that the studied co-medications are unlikely to have clinically relevant effects on trabectedin binding to plasma proteins at therapeutic concentrations. ..
  41. Soares D, Escargueil A, Poindessous V, Sarasin A, de Gramont A, Bonatto D, et al. Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743. Proc Natl Acad Sci U S A. 2007;104:13062-7 pubmed
    ..Because loss of repair proteins is common in human tumors, expression levels of selected repair factors may be useful in identifying patients particularly likely to benefit, or not, from treatment with ET-743. ..
  42. Marco E, David Cordonnier M, Bailly C, Cuevas C, Gago F. Further insight into the DNA recognition mechanism of trabectedin from the differential affinity of its demethylated analogue ecteinascidin ET729 for the triplet DNA binding site CGA. J Med Chem. 2006;49:6925-9 pubmed
    ..By means of molecular dynamics simulations of the precovalent complexes, we explain in atomic detail how such a simple structural modification brings about this notable change in the DNA-binding selectivity profiles of these two drugs. ..
  43. Carter N, Keam S. Trabectedin: a review of its use in soft tissue sarcoma and ovarian cancer. Drugs. 2010;70:355-76 pubmed publisher
  44. Brandon E, Sparidans R, Guijt K, Löwenthal S, Meijerman I, Beijnen J, et al. In vitro characterization of the human biotransformation and CYP reaction phenotype of ET-743 (Yondelis, Trabectidin), a novel marine anti-cancer drug. Invest New Drugs. 2006;24:3-14 pubmed
    ..Furthermore, ET-743 is conjugated by UGT and GST. This information could be important for interpretation of the pharmacokinetic data of clinical trials and prediction of drug-drug interactions. ..
  45. Manara M, Perdichizzi S, Serra M, Pierini R, Benini S, Hattinger C, et al. The molecular mechanisms responsible for resistance to ET-743 (Trabectidin; Yondelis) in the Ewing's sarcoma cell line, TC-71. Int J Oncol. 2005;27:1605-16 pubmed
  46. Abe K, Saitoh T, Horiguchi Y, Utsunomiya I, Taguchi K. Synthesis and neurotoxicity of tetrahydroisoquinoline derivatives for studying Parkinson's disease. Biol Pharm Bull. 2005;28:1355-62 pubmed
    ..In this article, we focus on the synthesis and pharmacological aspects of 1,2,3,4-tetrahydroisoquinoline derivatives in Parkinson's disease. ..
  47. Watson A, Li J, Schumacher C, De Gasparo M, Feng B, Thomas M, et al. The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice. Diabetologia. 2010;53:192-203 pubmed publisher
    ..This study demonstrates that ETA blockade with avosentan may provide an alternate therapeutic strategy for the treatment of diabetic micro- and macrovascular complications. ..
  48. Chen Y, Agarwal S, Shaik N, Chen C, Yang Z, Elmquist W. P-glycoprotein and breast cancer resistance protein influence brain distribution of dasatinib. J Pharmacol Exp Ther. 2009;330:956-63 pubmed publisher
    ..These transport systems play a significant role in limiting the CNS delivery of dasatinib and may have direct implications in the treatment of primary and metastatic brain tumors. ..
  49. Filip M, Antkiewicz Michaluk L, Zaniewska M, Frankowska M, Gołda A, Vetulani J, et al. Effects of 1-methyl-1,2,3,4-tetrahydroisoquinoline on the behavioral effects of cocaine in rats. J Physiol Pharmacol. 2007;58:625-39 pubmed
    The efficacy of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), a member of endogenous tetrahydroisoquinolines, in cocaine- and food-maintained responding in self-administration procedures under a fixed ratio 5 schedule of ..
  50. Wasik A, Romanska I, Antkiewicz Michaluk L. The effect of an endogenous compound 1-methyl-1,2,3,4,-tetrahydroisoquinoline on morphine-induced analgesia, dependence and neurochemical changes in dopamine metabolism in rat brain structures. J Physiol Pharmacol. 2007;58:235-52 pubmed
    1,2,3,4-Tetrahydroisoquinolines, among them the most interesting neuroprotective substance, an inhibitor of MAO, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), are endogenous compounds present in the central nervous system of mammals ..
  51. Cai T, Zou Z, Thomas J, Brieaddy L, Navarro H, Carroll F. Synthesis and in vitro opioid receptor functional antagonism of analogues of the selective kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3. J Med Chem. 2008;51:1849-60 pubmed publisher
    ..03 nM at the kappa receptor and 100- and 793-fold selectivity relative to the mu and delta receptors was the most potent and selective kappa opioid receptor antagonist identified. ..
  52. Jackson K, Carroll F, Negus S, Damaj M. Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward, and withdrawal in the mouse. Psychopharmacology (Berl). 2010;210:285-94 pubmed publisher
    ..The results from this study suggest that blockade of the KOR by selective KOR antagonists may be useful smoking cessation pharmacotherapies. ..
  53. Demetri G, Chawla S, von Mehren M, Ritch P, Baker L, Blay J, et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009;27:4188-96 pubmed publisher
    ..Trabectedin may now be considered an important new option to control advanced sarcomas in patients after failure of available standard-of-care therapies. ..