Genomes and Genes
Summary: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
- Qian P, Papiz M, Jackson P, Brindley A, Ng I, Olsen J, et al. Three-dimensional structure of the Rhodobacter sphaeroides RC-LH1-PufX complex: dimerization and quinone channels promoted by PufX. Biochemistry. 2013;52:7575-85 pubmed publisher..The structure of the RC-LH1-PufX complex explains the crucial role played by PufX in dimer formation, and it shows how quinone traffic traverses the LH1 complex as it shuttles between the RC and the cytochrome bc? complex. ..
- Singh A, Ahmad I, Akhter S, Jain G, Iqbal Z, Talegaonkar S, et al. Nanocarrier based formulation of Thymoquinone improves oral delivery: stability assessment, in vitro and in vivo studies. Colloids Surf B Biointerfaces. 2013;102:822-32 pubmed publisher..The effect of the treatment was confirmed by the histopathology of the liver microtome sections. ..
- Das S, Dey K, Dey G, Pal I, Majumder A, Maitichoudhury S, et al. Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma. PLoS ONE. 2012;7:e46641 pubmed publisher..TQ and DG, alone and in combination, inhibit cell proliferation and induce apoptosis in squamous cell carcinoma. The combination of TQ and DG is a potential antineoplastic therapy in this common skin cancer. ..
- He S, Zhang C, Shafi A, Sequeira M, Acquaviva J, Friedland J, et al. Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells irrespective of androgen receptor status or variant receptor expression. Int J Oncol. 2013;42:35-43 pubmed publisher..Together these data suggest that further investigation of ganetespib as a new therapeutic treatment for prostate cancer patients is warranted. ..
- Alam S, Khan Z, Mustafa G, Kumar M, Islam F, Bhatnagar A, et al. Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study. Int J Nanomedicine. 2012;7:5705-18 pubmed publisher..The high drug-targeting potential and efficiency demonstrates the significant role of the mucoadhesive properties of TQ-NP1. ..
- El Elimat T, Figueroa M, Raja H, Graf T, Adcock A, Kroll D, et al. Benzoquinones and terphenyl compounds as phosphodiesterase-4B inhibitors from a fungus of the order Chaetothyriales (MSX 47445). J Nat Prod. 2013;76:382-7 pubmed publisher..Of these, two were benzoquinones [betulinan A (1) and betulinan C (3)], and the third was a terphenyl compound, BTH-II0204-207:A (2)...
- Barrott J, Haystead T. Hsp90, an unlikely ally in the war on cancer. FEBS J. 2013;280:1381-96 pubmed publisher..We propose that in contrast to the majority of chemotherapeutics our growing armamentarium of investigational Hsp90 drugs represents an elegant choice that offers real hope in the long-term treatment of certain cancers. ..
- Li F, Rajendran P, Sethi G. Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway. Br J Pharmacol. 2010;161:541-54 pubmed publisher..Our study has identified STAT3 signalling as a target of TQ and has thus raised its potential application in the prevention and treatment of MM and other cancers. ..
- Palacios C, Martín Pérez R, López Pérez A, Pandiella A, Lopez Rivas A. Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis. Leuk Res. 2010;34:1533-8 pubmed publisher..The potential use of Hsp90 and autophagy inhibitors combinations as a therapeutic tool in MM is further discussed in our work. ..
- Chen F, Pandey D, Chadli A, Catravas J, Chen T, Fulton D. Hsp90 regulates NADPH oxidase activity and is necessary for superoxide but not hydrogen peroxide production. Antioxid Redox Signal. 2011;14:2107-19 pubmed publisher..We conclude that Hsp90 binds to the C-terminus of Noxes1-3 and 5 and is necessary for enzyme stability and superoxide production. Hsp90 does not bind to the C-terminus of Nox4 and is not required for hydrogen peroxide formation. ..
- Pallavi R, Roy N, Nageshan R, Talukdar P, Pavithra S, Reddy R, et al. Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug. J Biol Chem. 2010;285:37964-75 pubmed publisher..evansi growth in a mouse model of trypanosomiasis. In all, our biochemical characterization, drug interaction, and animal studies supported Hsp90 as a drug target and its inhibitor as a potential drug against protozoan diseases...
- Centenera M, Gillis J, Hanson A, Jindal S, Taylor R, Risbridger G, et al. Evidence for efficacy of new Hsp90 inhibitors revealed by ex vivo culture of human prostate tumors. Clin Cancer Res. 2012;18:3562-70 pubmed publisher..This approach, therefore, has the potential to enable more rational selection of therapeutic agents and biomarkers of response for clinical trials. ..
- Yu C, Wu P, Hsu J, Ho Y, Hsu L, Chang Y, et al. Ardisianone, a natural benzoquinone, efficiently induces apoptosis in human hormone-refractory prostate cancers through mitochondrial damage stress and survivin downregulation. Prostate. 2013;73:133-45 pubmed publisher..The data provide evidence supporting that ardisianone is a potential anticancer agent against HRPCs. ..
- Ou W, Hubert C, Corson J, Bueno R, Flynn D, Sugarbaker D, et al. Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma. Neoplasia. 2011;13:12-22 pubmed..These compelling proapoptotic and antiproliferative responses indicate that HSP90 inhibition warrants clinical evaluation as a novel therapeutic strategy in mesothelioma. ..
- Alhosin M, Ibrahim A, Boukhari A, Sharif T, Gies J, Auger C, et al. Anti-neoplastic agent thymoquinone induces degradation of ? and ? tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts. Invest New Drugs. 2012;30:1813-9 pubmed publisher..Furthermore, they highlight the interest of developing anti-cancer therapies that target directly tubulin rather than microtubules dynamics. ..
- Woo C, Kumar A, Sethi G, Tan K. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol. 2012;83:443-51 pubmed publisher..In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of thymoquinone with a focus on its molecular targets, and its possible role in the treatment of inflammatory diseases and cancer. ..
- Davenport J, Manjarrez J, Peterson L, Krumm B, Blagg B, Matts R. Gambogic acid, a natural product inhibitor of Hsp90. J Nat Prod. 2011;74:1085-92 pubmed publisher..The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors. ..
- Arteaga C. Why is this effective HSP90 inhibitor not being developed in HER2+ breast cancer?. Clin Cancer Res. 2011;17:4919-21 pubmed publisher..This combination is one of several HER2-targeted therapies that will significantly improve the outcome of patients with this subtype of breast cancer. ..
- Beloueche Babari M, Arunan V, Jackson L, Perusinghe N, Sharp S, Workman P, et al. Modulation of melanoma cell phospholipid metabolism in response to heat shock protein 90 inhibition. Oncotarget. 2010;1:185-97 pubmed..Our findings provide a basis for using metabolic changes as non-invasive indicators of Hsp90 inhibition and potentially as biomarkers of anticancer activity with Hsp90 drugs in malignant melanoma and possibly in other cancers. ..
- Alkharfy K, Al Daghri N, Al Attas O, Alokail M. The protective effect of thymoquinone against sepsis syndrome morbidity and mortality in mice. Int Immunopharmacol. 2011;11:250-4 pubmed publisher..1817 and 0.0851, respectively). This study gives strength to the potential clinical relevance of thymoquinone in sepsis-related morbidity and mortality reduction and suggests that human studies should be performed. ..
- Brandes A, Ward C, Ronen S. 17-allyamino-17-demethoxygeldanamycin treatment results in a magnetic resonance spectroscopy-detectable elevation in choline-containing metabolites associated with increased expression of choline transporter SLC44A1 and phospholipase A2. Breast Cancer Res. 2010;12:R84 pubmed publisher..As Hsp90 inhibitors enter routine clinical use, t-Cho could thus provide an easily detectable, noninvasive metabolic biomarker of Hsp90 inhibition in breast cancer patients. ..
- Roué G, Perez Galan P, Mozos A, Lopez Guerra M, Xargay Torrent S, Rosich L, et al. The Hsp90 inhibitor IPI-504 overcomes bortezomib resistance in mantle cell lymphoma in vitro and in vivo by down-regulation of the prosurvival ER chaperone BiP/Grp78. Blood. 2011;117:1270-9 pubmed publisher..These results suggest that targeting unfolded protein response activation by the inhibition of Hsp90 may be an attractive model for the design of a new bortezomib-based combination therapy for MCL. ..
- Modi S, Stopeck A, Linden H, Solit D, Chandarlapaty S, Rosen N, et al. HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res. 2011;17:5132-9 pubmed publisher..Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted. ..
- Vaseva A, Yallowitz A, Marchenko N, Xu S, Moll U. Blockade of Hsp90 by 17AAG antagonizes MDMX and synergizes with Nutlin to induce p53-mediated apoptosis in solid tumors. Cell Death Dis. 2011;2:e156 pubmed publisher..To our knowledge Nutlin+17AAG represents the first effective pharmacologic knockdown of MDMX. Our study identifies 17AAG as a promising synthetic lethal partner for a more efficient Nutlin-based therapy. ..
- Hussain A, Uddin S, Ahmed M, Bu R, Ahmed S, Abubaker J, et al. Prognostic significance of XIAP expression in DLBCL and effect of its inhibition on AKT signalling. J Pathol. 2010;222:180-90 pubmed publisher..In summary, our data suggest that XIAP expression is a poor prognostic factor in DLBCL and the XIAP-AKT relationship should be explored further as a potential therapeutic target in DLBCL. ..
- Ammar E, Gameil N, Shawky N, Nader M. Comparative evaluation of anti-inflammatory properties of thymoquinone and curcumin using an asthmatic murine model. Int Immunopharmacol. 2011;11:2232-6 pubmed publisher..On the other hand, CMN was a less potent inhibitor of all measured parameters, despite its superior inhibitory effect on TNF-? mRNA levels. ..
- Su D, Delaplane S, Luo M, Rempel D, Vu B, Kelley M, et al. Interactions of apurinic/apyrimidinic endonuclease with a redox inhibitor: evidence for an alternate conformation of the enzyme. Biochemistry. 2011;50:82-92 pubmed..Collectively, our results suggest that APE1 adopts a partially unfolded state, which we propose is the redox active form of the enzyme. ..
- Fishel M, Jiang Y, Rajeshkumar N, Scandura G, Sinn A, He Y, et al. Impact of APE1/Ref-1 redox inhibition on pancreatic tumor growth. Mol Cancer Ther. 2011;10:1698-708 pubmed publisher..These data indicate that E3330, inhibitor of APE1/Ref-1, has potential in pancreatic cancer and clinical investigation of APE1/Ref-1 molecular target is warranted. ..
- Kobayashi N, Toyooka S, Soh J, Yamamoto H, Dote H, Kawasaki K, et al. The anti-proliferative effect of heat shock protein 90 inhibitor, 17-DMAG, on non-small-cell lung cancers being resistant to EGFR tyrosine kinase inhibitor. Lung Cancer. 2012;75:161-6 pubmed publisher..These results suggested that 17-DMAG is a potential novel therapeutic agent for NSCLC patients with EGFR mutations with or without EGFR-TKI resistance. ..
- Floris G, Debiec Rychter M, Wozniak A, Stefan C, Normant E, Faa G, et al. The heat shock protein 90 inhibitor IPI-504 induces KIT degradation, tumor shrinkage, and cell proliferation arrest in xenograft models of gastrointestinal stromal tumors. Mol Cancer Ther. 2011;10:1897-908 pubmed publisher..The sequence of drug administration in the combination arms warrants further studies. ..
- Siegel D, Jagannath S, Vesole D, Borello I, Mazumder A, Mitsiades C, et al. A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma. Leuk Lymphoma. 2011;52:2308-15 pubmed publisher..Four patients had stable disease, demonstrating modest single-agent activity in relapsed or relapsed/refractory MM. ..
- Sequist L, Gettinger S, Senzer N, Martins R, Janne P, Lilenbaum R, et al. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol. 2010;28:4953-60 pubmed publisher..Grade 3 or higher liver function abnormalities were observed in nine patients (11.8%). IPI-504 has clinical activity in patients with NSCLC, particularly among patients with ALK rearrangements. ..
- Lam L, Zhang Z, Board P, Xun L. Reduction of benzoquinones to hydroquinones via spontaneous reaction with glutathione and enzymatic reaction by S-glutathionyl-hydroquinone reductases. Biochemistry. 2012;51:5014-21 pubmed publisher..Here we demonstrate that several benzoquinones spontaneously reacted with GSH to form GS-hydroquinones via Michael addition, and four GS-HQRs from yeast and ..
- Katragadda U, Teng Q, Rayaprolu B, Chandran T, Tan C. Multi-drug delivery to tumor cells via micellar nanocarriers. Int J Pharm. 2011;419:281-6 pubmed publisher..PEG-DSPE/TPGS mixed micelles may provide a novel and advantageous delivery approach for paclitaxel/17-AAG combination therapy. ..
- Huntoon C, Nye M, Geng L, Peterson K, Flatten K, Haluska P, et al. Heat shock protein 90 inhibition depletes LATS1 and LATS2, two regulators of the mammalian hippo tumor suppressor pathway. Cancer Res. 2010;70:8642-50 pubmed publisher..Taken together, these results identify LATS1 and LATS2 as novel HSP90 clients and show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells. ..
- Luo S, Wang T, Qin H, Lei H, Xia Y. Obligatory role of heat shock protein 90 in iNOS induction. Am J Physiol Cell Physiol. 2011;301:C227-33 pubmed publisher..In view of the essential role of Hsp90 in iNOS gene transactivation, targeting Hsp90 may represent a new approach to intervene iNOS expression in diseases. ..
- Hu R, Zhu K, Li Y, Yao K, Zhang R, Wang H, et al. Embelin induces apoptosis through down-regulation of XIAP in human leukemia cells. Med Oncol. 2011;28:1584-8 pubmed publisher..Taken together, these findings suggest that embelin results in human leukemia cells apoptosis through caspase-dependent mechanisms involving down-regulation of XIAP. ..
- Kelley M, Luo M, Reed A, Su D, Delaplane S, Borch R, et al. Functional analysis of novel analogues of E3330 that block the redox signaling activity of the multifunctional AP endonuclease/redox signaling enzyme APE1/Ref-1. Antioxid Redox Signal. 2011;14:1387-401 pubmed publisher..This progress in synthesizing and isolating biologically active novel E3330 analogues that effectively inhibit the APE1 redox function validates the utility of further translational anticancer therapeutic development. ..
- Fishel M, Colvin E, Luo M, Kelley M, Robertson K. Inhibition of the redox function of APE1/Ref-1 in myeloid leukemia cell lines results in a hypersensitive response to retinoic acid-induced differentiation and apoptosis. Exp Hematol. 2010;38:1178-88 pubmed publisher..Targeting of APE1/Ref-1 redox function may allow manipulation of the retinoid response with therapeutic implications. ..
- Kim M, Jo S, Ha K, Song J, Jang H, Kwon Y. Antimicrobial activities of 1,4-benzoquinones and wheat germ extract. J Microbiol Biotechnol. 2010;20:1204-9 pubmed..typhimurium (32 microgram/ml) and B. cereus (32 microgram/ml). The results suggest that wheat germ extract has potential for the development of natural antimicrobials and food preservatives for controlling foodborne pathogens. ..
- Gurung R, Lim S, Khaw A, Soon J, Shenoy K, Mohamed Ali S, et al. Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells. PLoS ONE. 2010;5:e12124 pubmed publisher..Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in the management for brain tumours. ..
- Regan P, Jacobs J, Wang G, Torres J, Edo R, Friedmann J, et al. Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma. Int J Oncol. 2011;38:105-12 pubmed..Together our data suggest that Hsp90 inhibition suppresses the growth of neuroblastoma through multiple cellular pathways and that MYC/MYCN destabilization is among the important consequences of Hsp90 inhibition. ..
- Mohany M, El Feki M, Refaat I, Garraud O, Badr G. Thymoquinone ameliorates the immunological and histological changes induced by exposure to imidacloprid insecticide. J Toxicol Sci. 2012;37:1-11 pubmed..Taken together, our data reveal the benefits of TQ supplementation for ameliorating IC toxicity by decreasing oxidative stress and enhancing immune efficiency. ..
- O Malley K, Langmann G, Ai J, Ramos Garcia R, Vessella R, Wang Z. Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance. Prostate. 2012;72:1117-23 pubmed publisher..Targeting Hsp90 or the mechanism by which HSP90 regulates androgen-independent AR nuclear localization and activation may lead to new approaches to prevent and/or treat castration-resistant prostate cancer. ..
- Uddin M, Park W, Kim Y, Pyon J, Park S. Effects of auxins on sorgoleone accumulation and genes for sorgoleone biosynthesis in sorghum roots. J Agric Food Chem. 2011;59:12948-53 pubmed publisher..Transcript accumulation was apparent for all genes, but particularly for DES2, which increased up to 475-fold and 180-fold following 72 h exposure to NAA and IBA, respectively, compared to no treatment...
- Winder P, Baker H, Linley P, Guzmán E, Pomponi S, Diaz M, et al. Neopetrosiquinones A and B, sesquiterpene benzoquinones isolated from the deep-water sponge Neopetrosia cf. proxima. Bioorg Med Chem. 2011;19:6599-603 pubmed publisherTwo new marine-derived sesquiterpene benzoquinones which we designate as neopetrosiquinones A (1) and B (2), have been isolated from a deep-water sponge of the family Petrosiidae...
- Badr G, Lefevre E, Mohany M. Thymoquinone inhibits the CXCL12-induced chemotaxis of multiple myeloma cells and increases their susceptibility to Fas-mediated apoptosis. PLoS ONE. 2011;6:e23741 pubmed publisher..In conclusion, we demonstrate the potent anti-myeloma activity of TQ, providing a rationale for further clinical evaluation. ..
- Oh W, Galsky M, Stadler W, Srinivas S, Chu F, Bubley G, et al. Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer. Urology. 2011;78:626-30 pubmed publisher..Therefore, additional evaluation in CRPC patients is not warranted. IPI-504 is being investigated at less-intensive doses and schedules in other tumor types. ..
- Morais T, Romoff P, Fávero O, Reimão J, Lourenço W, Tempone A, et al. Anti-malarial, anti-trypanosomal, and anti-leishmanial activities of jacaranone isolated from Pentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae). Parasitol Res. 2012;110:95-101 pubmed publisher..75 ?g/mL) and a selectivity index of 3. The obtained results suggested that jacaranone, as other similar secondary metabolites or synthetic analogs, might be useful tolls for drug design for in vivo studies against protozoan diseases. ..
- Iyer G, Morris M, Rathkopf D, Slovin S, Steers M, Larson S, et al. A phase I trial of docetaxel and pulse-dose 17-allylamino-17-demethoxygeldanamycin in adult patients with solid tumors. Cancer Chemother Pharmacol. 2012;69:1089-97 pubmed publisher..The recommended phase II dose is docetaxel 70 mg/m(2) and 17-AAG 500 mg/m(2). ..
- Moyer A, Fridley B, Jenkins G, Batzler A, Pelleymounter L, Kalari K, et al. Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011;120:33-41 pubmed publisher..If these observations are validated in future clinical studies, this SNP signal might represent a potential biomarker for risk of acetaminophen hepatotoxicity. The mechanisms responsible for this association remain unclear. ..
- Nawrat C, Lewis W, Moody C. Synthesis of amino-1,4-benzoquinones and their use in Diels-Alder approaches to the aminonaphthoquinone antibiotics. J Org Chem. 2011;76:7872-81 pubmed publisherA new protocol for the synthesis of protected amino-1,4-benzoquinones by oxidation of the corresponding 2,5-dimethoxyaniline derivatives using PhI(OAc)(2) or PhI(OCOCF(3))(2) in water containing 2.5% methanol is reported...
- Hung C, Tsai M, Wu Y, Wang R. Identification of heat-shock protein 90 beta in Japanese encephalitis virus-induced secretion proteins. J Gen Virol. 2011;92:2803-9 pubmed publisher..Our results show that Hsp90?, not Hsp90?, is present in the JEV-induced secretion medium and is required for JEV infectivity in BHK-21 cells. ..
- Millson S, Chua C, Roe S, Polier S, Solovieva S, Pearl L, et al. Features of the Streptomyces hygroscopicus HtpG reveal how partial geldanamycin resistance can arise with mutation to the ATP binding pocket of a eukaryotic Hsp90. FASEB J. 2011;25:3828-37 pubmed publisher..This is the first study to demonstrate that partial GdA resistance is possible by mutation within the ATP binding pocket of Hsp90. ..
- Richardson P, Badros A, Jagannath S, Tarantolo S, Wolf J, Albitar M, et al. Tanespimycin with bortezomib: activity in relapsed/refractory patients with multiple myeloma. Br J Haematol. 2010;150:428-37 pubmed publisher..The study was closed prematurely for resource-based reasons, precluding dose comparison. Nonetheless, antitumour activity was observed, with promising response rates and promising severity of peripheral neuropathy. ..
- Joshi P, Stoddart C. Impaired infectivity of ritonavir-resistant HIV is rescued by heat shock protein 90AB1. J Biol Chem. 2011;286:24581-92 pubmed publisher..These results suggest a possible role for HSP90AB1 in postentry HIV replication and may provide an attractive target for therapeutic intervention. ..
- Xie Q, Wondergem R, Shen Y, Cavey G, Ke J, Thompson R, et al. Benzoquinone ansamycin 17AAG binds to mitochondrial voltage-dependent anion channel and inhibits cell invasion. Proc Natl Acad Sci U S A. 2011;108:4105-10 pubmed publisher..We conclude that some of the effects of 17-AAG and other ansamycins are due to their effects on VDAC and that this may play a role in their clinical activity. ..