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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Potential Biological Targets Prediction, ADME Profiling, and Molecular Docking Studies of Novel Steroidal Products from Cunninghamella blakesleana

Author(s): Maria Yousuf*, Sidra Rafi, Urooj Ishrat, Alekberzadeh Shafiga, Gulnara Dashdamirova , Vazirova Leyla and Heydarov Iqbal

Volume 18, Issue 2, 2022

Published on: 08 June, 2021

Page: [288 - 305] Pages: 18

DOI: 10.2174/1573406417666210608143128

Price: $65

Abstract

Background: New potential biological targets prediction through inverse molecular docking technique is another smart strategy to forecast the possibility of compounds being biologically active against various target receptors.

Objective: In this case of designed study, we screened our recently obtained novel acetylenic steroidal biotransformed products [(1) 8- β-methyl-14-α-hydroxyΔ4tibolone (2) 9-α-HydroxyΔ4 tibolone (3) 8- β-methyl-11- β-hydroxyΔ4tibolone (4) 6- β-hydroxyΔ4tibolone, (5) 6- β-9-α-dihydroxyΔ4tibolone (6) 7- β-hydroxyΔ4tibolone)] from fungi Cunninghemella Blakesleana to predict their possible biological targets and profiling of ADME properties.

Methods: The prediction of pharmacokinetic properties, membrane permeability, and bioavailability radar properties was carried out by using Swiss target prediction and Swiss ADME tools, respectively. These metabolites were also subjected to predict the possible mechanism of action along with associated biological network pathways by using Reactome database.

Results: All the six screened compounds possessed excellent drug ability criteria and exhibited exceptionally excellent non-inhibitory potential against all five isozymes of the CYP450 enzyme complex, including CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4. All the screened compounds are lying within the acceptable pink zone of bioavailability radar and showing excellent descriptive properties. Compounds [1-4 & 6] are showing high BBB (Blood Brain Barrier) permeation, while compound 5 is exhibiting high HIA (Human Intestinal Absorption) property of (Egan Egg).

Conclusion: In conclusion, the results of this study smartly reveal that in-silico based studies are considered to provide robustness towards a rational drug design and development approach; therefore, in this way, it helps to avoid the possibility of failure of drug candidates in the later experimental stages of drug development phases.

Keywords: Cunninghemella blakesleana, swiss target prediction, Swiss ADME, BOIELD-Egg pharmacokinetics, molecular docking, blood brain barrier (BBB), human intestinal absorption (HIA), reactome data-base, tibolone.

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[1]
Zambrowicz, B.P.; Sands, A.T. Knockouts model the 100 best-selling drugs--will they model the next 100? Nat. Rev. Drug Discov., 2003, 2(1), 38-51.
[http://dx.doi.org/10.1038/nrd987] [PMID: 12509758]
[2]
Oprea, T.I.; Bauman, J.E.; Bologa, C.G.; Buranda, T.; Chigaev, A.; Edwards, B.S.; Jarvik, J.W.; Gresham, H.D.; Haynes, M.K.; Hjelle, B.; Hromas, R.; Hudson, L.; Mackenzie, D.A.; Muller, C.Y.; Reed, J.C.; Simons, P.C.; Smagley, Y.; Strouse, J.; Surviladze, Z.; Thompson, T.; Ursu, O.; Waller, A.; Wandinger-Ness, A.; Winter, S.S.; Wu, Y.; Young, S.M.; Larson, R.S.; Willman, C.; Sklar, L.A. Drug repurposing from an academic perspective. Drug Discov. Today Ther. Strateg., 2011, 8(3-4), 61-69.
[http://dx.doi.org/10.1016/j.ddstr.2011.10.002] [PMID: 22368688]
[3]
Jorgensen, W.L. Efficient drug lead discovery and optimization. Acc. Chem. Res., 2009, 42(6), 724-733.
[http://dx.doi.org/10.1021/ar800236t] [PMID: 19317443]
[4]
Imming, P.; Sinning, C.; Meyer, A. Drugs, their targets and the nature and number of drug targets. Nat. Rev. Drug Discov., 2006, 5(10), 821-834.
[http://dx.doi.org/10.1038/nrd2132] [PMID: 17016423]
[5]
Gaulton, A.; Kale, N.; van Westen, G.J.; Bellis, L.J.; Bento, A.P.; Davies, M.; Overington, J.P. The ChEMBL bioactivity database: an update. Scientific Data, 2013, 2(2), 15003-150032.
[6]
Irwin, J.J.; Sterling, T.; Mysinger, M.M.; Bolstad, E.S.; Coleman, R.G. ZINC: a free tool to discover chemistry for biology. J. Chem. Inf. Model., 2012, 52(7), 1757-1768.
[http://dx.doi.org/10.1021/ci3001277] [PMID: 22587354]
[7]
Mestres, J.; Gregori-Puigjané, E.; Valverde, S.; Solé, R.V. The topology of drug-target interaction networks: implicit dependence on drug properties and target families. Mol. Biosyst., 2009, 5(9), 1051-1057.
[http://dx.doi.org/10.1039/b905821b] [PMID: 19668871]
[8]
Schneider, G. Virtual screening: an endless staircase? Nat. Rev. Drug Discov., 2010, 9(4), 273-276.
[http://dx.doi.org/10.1038/nrd3139] [PMID: 20357802]
[9]
Lounkine, E.; Keiser, M.J.; Whitebread, S.; Mikhailov, D.; Hamon, J.; Jenkins, J.L.; Lavan, P.; Weber, E.; Doak, A.K.; Côté, S.; Shoichet, B.K.; Urban, L. Large-scale prediction and testing of drug activity on side-effect targets. Nature, 2012, 486(7403), 361-367.
[http://dx.doi.org/10.1038/nature11159] [PMID: 22722194]
[10]
Di Fiore, P.P.; Pelicci, P.G. Cell regulation. Curr. Methods Opin. Cell Biol., 2003, 2(15), 125-127.
[http://dx.doi.org/10.1016/S0955-0674(03)00011-5] [PMID: 12581382]
[11]
Willett, P. Similarity searching using 2D structural fingerprints. Methods Mol. Biol., 2011, 672, 133-158.
[http://dx.doi.org/10.1007/978-1-60761-839-3_5] [PMID: 20838967]
[12]
Ballester, P.J.; Richards, W.G. Ultrafast shape recognition to search compound databases for similar molecular shapes. J. Comput. Chem., 2007, 28(10), 1711-1723.
[http://dx.doi.org/10.1002/jcc.20681] [PMID: 17342716]
[13]
Sastry, G.M.; Dixon, S.L.; Sherman, W. Rapid shape-based ligand alignment and virtual screening method based on atom/feature-pair similarities and volume overlap scoring. J. Chem. Inf. Model., 2011, 51(10), 2455-2466.
[http://dx.doi.org/10.1021/ci2002704] [PMID: 21870862]
[14]
Liu, X.; Jiang, H.; Li, H. SHAFTS: a hybrid approach for 3D molecular similarity calculation. 1. Method and assessment of virtual screening. J. Chem. Inf. Model., 2011, 51(9), 2372-2385.
[http://dx.doi.org/10.1021/ci200060s] [PMID: 21819157]
[15]
Armstrong, M.S.; Finn, P.W.; Morris, G.M.; Richards, W.G. Improving the accuracy of ultrafast ligand-based screening: incorporating lipophilicity into ElectroShape as an extra dimension. J. Comput. Aided Mol. Des., 2011, 25(8), 785-790.
[http://dx.doi.org/10.1007/s10822-011-9463-8] [PMID: 21822723]
[16]
Pérez-Nueno, V.I.; Venkatraman, V.; Mavridis, L.; Ritchie, D.W. Detecting drug promiscuity using Gaussian ensemble screening. J. Chem. Inf. Model., 2012, 52(8), 1948-1961.
[http://dx.doi.org/10.1021/ci3000979] [PMID: 22747187]
[17]
Armstrong, M.S.; Morris, G.M.; Finn, P.W.; Sharma, R.; Moretti, L.; Cooper, R.I.; Richards, W.G. ElectroShape: fast molecular similarity calculations incorporating shape, chirality and electrostatics. J. Comput. Aided Mol. Des., 2010, 24(9), 789-801.
[http://dx.doi.org/10.1007/s10822-010-9374-0] [PMID: 20614163]
[18]
Gfeller, D.; Grosdidier, A.; Wirth, M.; Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: a web server for target prediction of bioactive small molecules.Nucleic Acids Res., 2014, 42(Web Server issue), W32-8.,
[http://dx.doi.org/10.1093/nar/gku293] [PMID: 24792161]
[19]
Gfeller, D.; Michielin, O.; Zoete, V. Shaping the interaction landscape of bioactive molecules. Bioinformatics, 2013, 29(23), 3073-3079.
[http://dx.doi.org/10.1093/bioinformatics/btt540] [PMID: 24048355]
[20]
Zivanovic, S.; Colizzi, F.; Moreno, D.; Hospital, A.; Soliva, R.; Orozco, M. Exploring the conformational landscape of bioactive small molecules. J. Chem. Theory Comput., 2020, 16(10), 6575-6585.
[http://dx.doi.org/10.1021/acs.jctc.0c00304] [PMID: 32786895]
[21]
O’Boyle, N.M.; Banck, M.; James, C.A.; Morley, C.; Vandermeersch, T.; Hutchison, G.R. Open Babel: An open chemical toolbox. J. Cheminform., 2011, 3, 33.
[http://dx.doi.org/10.1186/1758-2946-3-33] [PMID: 21982300]
[22]
Daina, A.; Michielin, O.; Zoete, V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res., 2019, 47(W1), W357-W364. [Antoine DOlivier MVincent Z
[http://dx.doi.org/10.1093/nar/gkz382] [PMID: 31106366]
[23]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[24]
Antoine, D.; Vincent, Z. A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem, 2016, 11, 1117-1121.
[25]
Chen, N.H.; Reith, M.E.; Quick, M.W. Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6. Pflugers Arch., 2004, 447(5), 519-531.
[http://dx.doi.org/10.1007/s00424-003-1064-5] [PMID: 12719981]
[26]
Jackson, S.E. Hsp90: structure and function. Top. Curr. Chem., 2013, 328, 155-240.
[http://dx.doi.org/10.1007/128_2012_356] [PMID: 22955504]
[27]
Li, J.; Buchner, J. Structure, function and regulation of the hsp90 machinery. Biomed. J., 2013, 36(3), 106-117.
[http://dx.doi.org/10.4103/2319-4170.113230] [PMID: 23806880]
[28]
Echeverria, P.C.; Picard, D. Molecular chaperones, essential partners of steroid hormone receptors for activity and mobility. Biochim. Biophys. Acta, 2010, 1803(6), 641-649.
[http://dx.doi.org/10.1016/j.bbamcr.2009.11.012] [PMID: 20006655]
[29]
Kurian, M.A.; Gissen, P.; Smith, M.; Heales, S., Jr; Clayton, P.T. The monoamine neurotransmitter disorders: an expanding range of neurological syndromes. Lancet Neurol., 2011, 10(8), 721-733.
[http://dx.doi.org/10.1016/S1474-4422(11)70141-7] [PMID: 21777827]
[30]
Schweikhard, E.S.; Ziegler, C.M. Amino acid secondary transporters: toward a common transport mechanism. Curr. Top. Membr., 2012, 70, 1-28.
[http://dx.doi.org/10.1016/B978-0-12-394316-3.00001-6] [PMID: 23177982]
[31]
Bröer, S.; Gether, U. The solute carrier 6 family of transporters. Br. J. Pharmacol., 2012, 167(2), 256-278.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01975.x] [PMID: 22519513]
[32]
Supratim, C.; Ronald, F. Chanderbhan Amino acid secondary transporters Nutraceuticals, 2016.
[33]
Lambert, E.; Lambert, G.W. Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome. Front. Physiol., 2014, 5, 280.
[http://dx.doi.org/10.3389/fphys.2014.00280] [PMID: 25120493]
[34]
James, V.M.; Gill, J.L.; Topf, M.; Harvey, R.J. Molecular mechanisms of glycine transporter GlyT2 mutations in startle disease. Biol. Chem., 2012, 393(4), 283-289.
[http://dx.doi.org/10.1515/bc-2011-232] [PMID: 22114948]
[35]
Bode, A.; Lynch, J.W. The impact of human hyperekplexia mutations on glycine receptor structure and function. Mol. Brain, 2014, 7, 2.
[http://dx.doi.org/10.1186/1756-6606-7-2] [PMID: 24405574]
[36]
Bulun, S.E. Aromatase and estrogen receptor α deficiency. Fertil. Steril., 2014, 101(2), 323-329.
[http://dx.doi.org/10.1016/j.fertnstert.2013.12.022] [PMID: 24485503]
[37]
Huang, C.H.; Mandelker, D.; Schmidt-Kittler, O.; Samuels, Y.; Velculescu, V.E.; Kinzler, K.W.; Vogelstein, B.; Gabelli, S.B.; Amzel, L.M. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science, 2007, 318(5857), 1744-1748.
[http://dx.doi.org/10.1126/science.1150799] [PMID: 18079394]
[38]
Zhao, J.J.; Liu, Z.; Wang, L.; Shin, E.; Loda, M.F.; Roberts, T.M. The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc. Natl. Acad. Sci. USA, 2005, 102(51), 18443-18448.
[http://dx.doi.org/10.1073/pnas.0508988102] [PMID: 16339315]
[39]
Miled, N.; Yan, Y.; Hon, W.C.; Perisic, O.; Zvelebil, M.; Inbar, Y.; Schneidman-Duhovny, D.; Wolfson, H.J.; Backer, J.M.; Williams, R.L. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science, 2007, 317(5835), 239-242.
[http://dx.doi.org/10.1126/science.1135394] [PMID: 17626883]
[40]
Horn, S.; Bergholz, U.; Jücker, M.; McCubrey, J.A.; Trümper, L.; Stocking, C.; Bäsecke, J. Mutations in the catalytic subunit of class IA PI3K confer leukemogenic potential to hematopoietic cells. Oncogene, 2008, 27(29), 4096-4106.
[http://dx.doi.org/10.1038/onc.2008.40] [PMID: 18317450]
[41]
Hediger, M.A.; Clémençon, B.; Burrier, R.E.; Bruford, E.A. The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol. Aspects Med., 2013, 34(2-3), 95-107.
[http://dx.doi.org/10.1016/j.mam.2012.12.009] [PMID: 23506860]
[42]
Durand, E.; Boutin, P.; Meyre, D.; Charles, M.A.; Clément, K.; Dina, C.; Froguel, P. Polymorphisms in the amino acid transporter solute carrier family 6 (neurotransmitter transporter) member 14 gene contribute to polygenic obesity in French Caucasians. Diabetes, 2004, 53(9), 2483-2486.
[http://dx.doi.org/10.2337/diabetes.53.9.2483] [PMID: 15331564]
[43]
Suviolahti, E.; Oksanen, L.J.; Ohman, M.; Cantor, R.M.; Ridderstrale, M.; Tuomi, T.; Kaprio, J.; Rissanen, A.; Mustajoki, P.; Jousilahti, P.; Vartiainen, E.; Silander, K.; Kilpikari, R.; Salomaa, V.; Groop, L.; Kontula, K.; Peltonen, L.; Pajukanta, P. The SLC6A14 gene shows evidence of association with obesity. J. Clin. Invest., 2003, 112(11), 1762-1772.
[http://dx.doi.org/10.1172/JCI200317491] [PMID: 14660752]
[44]
Jungnickel, K.E.J.; Parker, J.L.; Simon, N. Structural basis for amino acid transport by the CAT family of SLC7 transporters. Nat. Commun., 2018, 9, 550.
[45]
Aqeilan, R.I.; Donati, V.; Palamarchuk, A.; Trapasso, F.; Kaou, M.; Pekarsky, Y.; Sudol, M.; Croce, C.M. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res., 2005, 65(15), 6764-6772.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1150] [PMID: 16061658]
[46]
Cheng, Q.C.; Tikhomirov, O.; Zhou, W.; Carpenter, G. Ectodomain cleavage of ErbB-4: characterization of the cleavage site and m80 fragment. J. Biol. Chem., 2003, 278(40), 38421-38427.
[http://dx.doi.org/10.1074/jbc.M302111200] [PMID: 12869563]
[47]
Rio, C.; Buxbaum, J.D.; Peschon, J.J.; Corfas, G. Tumor necrosis factor-alpha-converting enzyme is required for cleavage of erbB4/HER4. J. Biol. Chem., 2000, 275(14), 10379-10387.
[http://dx.doi.org/10.1074/jbc.275.14.10379] [PMID: 10744726]
[48]
Ishibashi, K.; Fukumoto, Y.; Hasegawa, H.; Abe, K.; Kubota, S.; Aoyama, K.; Kubota, S.; Nakayama, Y.; Yamaguchi, N. Nuclear ErbB4 signaling through H3K9me3 is antagonized by EGFR-activated c-Src. J. Cell Sci., 2013, 126(Pt 2), 625-637.
[http://dx.doi.org/10.1242/jcs.116277] [PMID: 23230144]
[49]
Komuro, A.; Nagai, M.; Navin, N.E.; Sudol, M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J. Biol. Chem., 2003, 278(35), 33334-33341.
[http://dx.doi.org/10.1074/jbc.M305597200] [PMID: 12807903]
[50]
Rameh, L.E.; Tolias, K.F.; Duckworth, B.C.; Cantley, L.C. A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature, 1997, 390(6656), 192-196.
[http://dx.doi.org/10.1038/36621] [PMID: 9367159]
[51]
Clarke, J.H.; Emson, P.C.; Irvine, R.F. Localization of phosphatidylinositol phosphate kinase IIgamma in kidney to a membrane trafficking compartment within specialized cells of the nephron. Am. J. Physiol. Renal Physiol., 2008, 295(5), F1422-F1430.
[http://dx.doi.org/10.1152/ajprenal.90310.2008] [PMID: 18753295]
[52]
Clarke, J.H.; Wang, M.; Irvine, R.F. Localization, regulation and function of type II phosphatidylinositol 5-phosphate 4-kinases. Adv. Enzyme Regul., 2010, 50(1), 12-18.
[http://dx.doi.org/10.1016/j.advenzreg.2009.10.006] [PMID: 19896968]
[53]
Clarke, J.H.; Irvine, R.F. Evolutionarily conserved structural changes in phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) isoforms are responsible for differences in enzyme activity and localization. Biochem. J., 2013, 454(1), 49-57.
[http://dx.doi.org/10.1042/BJ20130488] [PMID: 23758345]
[54]
Clarke, J.H.; Giudici, M.L.; Burke, J.E.; Williams, R.L.; Maloney, D.J.; Marugan, J.; Irvine, R.F. The function of phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ) explored using a specific inhibitor that targets the PI5P-binding site. Biochem. J., 2015, 466(2), 359-367.
[http://dx.doi.org/10.1042/BJ20141333] [PMID: 25495341]
[55]
Schneider, S. Inositol transport proteins. FEBS Lett., 2015, 589(10), 1049-1058.
[http://dx.doi.org/10.1016/j.febslet.2015.03.012] [PMID: 25819438]
[56]
Pajor, A.M. Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters. Pflugers Arch., 2006, 451(5), 597-605.
[http://dx.doi.org/10.1007/s00424-005-1487-2] [PMID: 16211368]
[57]
Morris, M.E.; Felmlee, M.A. Overview of the proton-coupled MCT (SLC16A) family of transporters: characterization, function and role in the transport of the drug of abuse gamma-hydroxybutyric acid. AAPS J., 2008, 10(2), 311-321.
[http://dx.doi.org/10.1208/s12248-008-9035-6] [PMID: 18523892]
[58]
Bressler, J.P.; Olivi, L.; Cheong, J.H.; Kim, Y.; Maerten, A.; Bannon, D. Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities. Hum. Exp. Toxicol., 2007, 26(3), 221-229.
[http://dx.doi.org/10.1177/0960327107070573] [PMID: 17439925]
[59]
Zhang, X.; Gan, L.; Pan, H.; Guo, S.; He, X.; Olson, S.T.; Mesecar, A.; Adam, S.; Unterman, T.G. Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding. J. Biol. Chem., 2002, 277(47), 45276-45284.
[http://dx.doi.org/10.1074/jbc.M208063200] [PMID: 12228231]
[60]
Yoshida, C.A.; Yamamoto, H.; Fujita, T.; Furuichi, T.; Ito, K.; Inoue, K.; Yamana, K.; Zanma, A.; Takada, K.; Ito, Y.; Komori, T. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev., 2004, 18(8), 952-963.
[http://dx.doi.org/10.1101/gad.1174704] [PMID: 15107406]
[61]
Li, C.; Jiang, J.; Zheng, Z.; Lee, K.S.; Zhou, Y.; Chen, E.; Culiat, C.T.; Qiao, Y.; Chen, X.; Ting, K.; Zhang, X.; Soo, C. Neural EGFL-like 1 is a downstream regulator of runt-related transcription factor 2 in chondrogenic differentiation and maturation. Am. J. Pathol., 2017, 187(5), 963-972.
[http://dx.doi.org/10.1016/j.ajpath.2016.12.026] [PMID: 28302495]
[62]
Miller, W.L. Disorders of androgen biosynthesis. Semin. Reprod. Med., 2002, 20(3), 205-216.
[http://dx.doi.org/10.1055/s-2002-35385] [PMID: 12428201]
[63]
Kim, T.; Pazhoor, S.; Bao, M.; Zhang, Z.; Hanabuchi, S.; Facchinetti, V.; Bover, L.; Plumas, J.; Chaperot, L.; Qin, J.; Liu, Y.J. Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA, 2010, 107(34), 15181-15186.
[http://dx.doi.org/10.1073/pnas.1006539107] [PMID: 20696886]
[64]
Srilatha, R.; Keith, R.S.; Pengxiang, H.; Pamela, M.R.; Amanda, K.N.; Don, B. McClure; Lorri, L.B.; Sepideh, K.; 4 Thomas, P.B.; Fraydoon, R. Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REVERBbeta. Nat. Struct. Mol. Biol., 2007, 14, 1207-1213.
[65]
Phelan, C.A.; Gampe, R.T., Jr; Lambert, M.H.; Parks, D.J.; Montana, V.; Bynum, J.; Broderick, T.M.; Hu, X.; Williams, S.P.; Nolte, R.T.; Lazar, M.A. Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction. Nat. Struct. Mol. Biol., 2010, 17(7), 808-814.
[http://dx.doi.org/10.1038/nsmb.1860] [PMID: 20581824]
[66]
Yin, L.; Wu, N.; Lazar, M.A. Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. Nucl. Recept. Signal., 2010, 8e001
[http://dx.doi.org/10.1621/nrs.08001] [PMID: 20414452]
[67]
Yin, L.; Wu, N.; Curtin, J.C.; Qatanani, M.; Szwergold, N.R.; Reid, R.A.; Waitt, G.M.; Parks, D.J.; Pearce, K.H.; Wisely, G.B.; Lazar, M.A. Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways. Science, 2007, 318(5857), 1786-1789.
[http://dx.doi.org/10.1126/science.1150179] [PMID: 18006707]
[68]
Scarpulla, R.C. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim. Biophys. Acta, 2011, 1813(7), 1269-1278.
[http://dx.doi.org/10.1016/j.bbamcr.2010.09.019] [PMID: 20933024]
[69]
Cantó, C.; Auwerx, J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr. Opin. Lipidol., 2009, 20(2), 98-105.
[http://dx.doi.org/10.1097/MOL.0b013e328328d0a4] [PMID: 19276888]
[70]
Gurd, B.J.; Yoshida, Y.; McFarlan, J.T.; Holloway, G.P.; Moyes, C.D.; Heigenhauser, G.J.; Spriet, L.; Bonen, A. Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2011, 301(1), R67-R75.
[http://dx.doi.org/10.1152/ajpregu.00417.2010] [PMID: 21543634]
[71]
Philp, A.; Chen, A.; Lan, D.; Meyer, G.A.; Murphy, A.N.; Knapp, A.E.; Olfert, I.M.; McCurdy, C.E.; Marcotte, G.R.; Hogan, M.C.; Baar, K.; Schenk, S. Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise. J. Biol. Chem., 2011, 286(35), 30561-30570.
[http://dx.doi.org/10.1074/jbc.M111.261685] [PMID: 21757760]
[72]
Cantó, C.; Gerhart-Hines, Z.; Feige, J.N.; Lagouge, M.; Noriega, L.; Milne, J.C.; Elliott, P.J.; Puigserver, P.; Auwerx, J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature, 2009, 458(7241), 1056-1060.
[http://dx.doi.org/10.1038/nature07813] [PMID: 19262508]
[73]
Regan Anderson, T.M.; Peacock, D.L.; Daniel, A.R.; Hubbard, G.K.; Lofgren, K.A.; Girard, B.J.; Schörg, A.; Hoogewijs, D.; Wenger, R.H.; Seagroves, T.N.; Lange, C.A. Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression. Cancer Res., 2013, 73(18), 5810-5820.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0523] [PMID: 23928995]
[74]
Pires, I.M.; Blokland, N.J.; Broos, A.W.; Poujade, F.A.; Senra, J.M.; Eccles, S.A.; Span, P.N.; Harvey, A.J.; Hammond, E.M. HIF-1α-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion. Cancer Biol. Ther., 2014, 15(10), 1350-1357.
[http://dx.doi.org/10.4161/cbt.29822] [PMID: 25019382]

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