2019-2015年

2019-2015年

Receptor Antagonists Bearing a Pentafluorosulfanyl (SF5) Group.
Mori, S.; Tsuemoto, N.; Kasagawa, T.; Nakano, E.; Fujii, S.; Kagechika, H.
Chem. Pharm. Bull. 2019, 67(12), 1278-1283. DOI: 10.1248/cpb.c19-00522.
A Polarity-Sensitive Fluorescent Amino Acid and its Incorporation into Peptides for the Ratiometric Detection of Biomolecular Interactions.
Yokoo, H.; Kagechika, H.; Ohsaki, A; Hirano T. A
ChemPlusChem 2019, 84, 1716-1719. DOI: 10.1002/cplu.201900489
A New LC-MS Assay for the Quantitative Analysis of Vitamin K Metabolites in Human Urine.
McDonald, M. G.; Yeung, C. K.; Teitelbaum, A. M.; Johnson, A. L.; Fujii, S.; Kagechika, H.; Rettie, A. E.
J. Lipid Res. 2019, 60(4), 892-899. DOI: 10.1194/jlr.D087916
Two new alkaloids from Crinum asiaticum var. japonicum.
Endo, Y.; Sugiura, Y.; Funasaki, M.; Kagechika, H.; Ishibashi, M.; Ohsaki, A.
J. Nat. Med. 2019, 73, 648-652. DOI: 10.1007/s11418-019-01304-9
Design, synthesis and biological evaluation of novel nonsteroidal progesterone receptor antagonists based on phenylamino-1,3,5-tirazine scaffold.
Kaitoh, K.; Nakatsu, A.; Mori, S.; Kagechika, H.; Hashimoto, Y.; Fujii,S.
Chem. Pharm. Bull. 2019, 67(6), 566-575. DOI: 10.1248/cpb.c19-00094
A new regulatory mechanism for Raf kinase activation, retinoic acid-bound Crabp1.
Park, S. W.; Nhieu, J.; Persaud, S. D.; Miller, M. C.; Xia, Y.; Lin, Y.-W.; Lin, Y.-L.; Kagechika, H.; Mayo, K. H.; Wei, L/-N.
Sci. Rep. 2019, 9, 10929. DOI: 10.1038/s41598-019-47354-7
Development of Novel Lithocholic Acid Derivatives as Vitamin D Receptor Agonists. Bioorg.
Masuno, H.; Kazui, Y.; Tanatani, A.; Fujii, S.; Kawachi, E.; Ikura, T.; Ito, N.; Yamamoto, K.; Kagechika, H.
Bioorg. Med. Chem. 2019, 27, 3674-3681. DOI: 10.1016/j.bmc.2019.07.003
Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay.
Mori, S.; Iinuma, H.; Manaka, N.; Ishigami-Yuasa, M.; Murayama, T.; Nishijima, Y.; Sakurai, A.; Arai, R.; Kurebayashi, N.; Sakurai, T.; Kagechika, H.
Eur. J. Med. Chem. 2019, 179, 837-848. DOI: 10.1016/j.ejmech.2019.06.076
Design and synthesis of cyclohexyl-p-carborane derivatives as a new class of progesterone receptor antagonists.
Fujii, S.; Yanagida, N.; Mori, S.; Kawachi, E.; Kagechika, H.
Heterocycles 2019, 99, 425-445. DOI: 10.3987/COM-18-S(F)38
Spontaneous Chiral Resolution of N,N’-Diarylsquaramides : Formation of Various Types of One-handed Helical Networks During Crystallization.
Kanda, M.; Urushibara, Ko.; Park, S.; Fujii, S.; Masu, H.; Katagiri, K.; Azumaya, I.; Kagechika, H.; Tanatani, A.
Tetrahedron 2019, 75, 2771-2777. DOI: 10.1016/j.tet.2019.03.049
Class IIb HDAC inhibition enhances the inhibitory effect of Am80, a synthetic retinoid, in prostate cancer.
Ishigami-Yuasa, M.; Ekimoto, H.; Kagechika, H.
Biol. Pharm. Bull. 2019, 42, 448-452. DOI: 10.1248/bpb.b18-00782
Highlighted Paper selected by Editor-in-Chie
Structure-Activity Relationship of Novel Androgen Receptor Antagonists Bearing a (Benzoylaminophenoxy)phenol Pharmacophore.
Kazui, Y.; Fujii, S.*; Yamada, A.; Ishigami-Yuasa, M.; Kagechika, H.; Tanatani, A
Bioorg. Med. Chem. 2018, 26, 5118-5127. DOI: 10.1016/j.bmc.2018.09.008
Prevention of acute liver injury by suppressing plasma kallikrein-dependent activation of latent TGF-b.
Li, M.; Qin, X.-Y.; Furutani, Y.; Inoue, I.; Sekihara, S.; Kagechika, H.; Kojima S.
Biochem. Biophys. Res. Chem. 2018, 504, 857-864. DOI: 10.1016/j.bbrc.2018.09.026
HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, preventsischemia-induced neuronal damage.
Loppi, S.; Kolosowska, N.; K?rkk?inen, O.; Korhonen, P.; Huuskonen, M.; Grubman, A.; Dhungana, H.; Wojciechowski, S.; Pomeshchik, Y.; Giordano, M.; Kagechika, H.; White, A.; Auriola, S.; Koistinaho, J.; Landreth, G.; Hanhineva, K.; Kanninen, K.; Malm, T.
Brain Behav. Immunol. 2018, 73, 670-681. DOI: 10.1016/j.bbi.2018.07.021
Development of novel inhibitors for histone methyltransferase SET7/9 based on cyproheptadine.
Hirano, T.; Fujiwara, T.; Niwa, H.; Hirano, M.; Ohira, K.; Okazaki, Y.; Sato, S.; Umehara, T.; Maemoto, Y.; Ito, A.; Yoshida, M.; Kagechika, H.
ChemMedChem 2018, 13, 1530-1540. DOI: 10.1002/cmdc.201800233
Novel non-steroidal progesterone receptor (PR) antagonists with a phenanthridinone skeleton.
Nishiyama, Y.; Mori, S.; Makishima, M.; Fujii, S.; Kagechika, H.; Hashimoto, Y.; Ishikawa, M.
ACS Med. Chem. Lett. 2018, 9, 641-645. DOI: 10.1021/acsmedchemlett.8b00058
Development of biotin-retinoid conjugates as chemical probes for analysis of retinoid function.
Fujii, S.; Mori, S.; Kagechika, H.; Parra, M. A. M.*; Gronemeyer, H.
Bioorg. Med. Chem. Lett. 2018, 28, 2442-2445. DOI: 10.1016/j.bmcl.2018.06.011
Efficient High-Throughput Screening by Endoplasmic Reticulum Ca2+ Measurement to Identify Inhibitors of Ryanodine Receptor Ca2+-Release Channels.
Murayama, T.; Kurebayashi, Ishigami-Yuasa, M.; Mori, A.; Suzuki, Y.; Akima, R.; Ogawa, H.; Suzuki, J.; Kanemaru, K.; Oyamada, H.; Kiuchi, Y.; Iino, K.; Kagechika, H.; Sakurai, T.
Mol. Pharmacol. 2018, 94, 722-730. DOI: 10.1124/mol.117.111468
Characterization and comparison of transcriptional activities of the retinoid X receptors by various organotin compounds in three prosobranch gastropods; Thais clavigera, Nucella lapillus and Babylonia japonica.
Urushitani, H.; Katsu, Y.; Kagechika, H.; Sousa, A. C. A.; Barroso, C. M.; Ohta, Y.; Shiraishi, H.; Iguchi, T.; Horiguchi, T.
Aquatic Toxicol. 2018, 199, 103-155. DOI: 10.1016/j.aquatox.2018.03.029
Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid.
Qin, X.-Y.; Suzuki, H.; Honda, M.; Okada, H.; Kaneko, S.; Inoue, I.; Ebisui, E.; Hashimoto, K.; Carninci, P.; Kanki, K.; Tatsukawa, H.; Ishibashi, N.; Masaki, T.; Matsuura, T.; Kagechika, H.; Toriguchi, K.; Hatano, E.; Shirakami, Y.; Shiota, G.; Shimizu, M.; Moriwaki, H.; Kojima, S.
Proc. Nat. Acad. Sci. USA 2018, 115 (19), 4969-4974. DOI: 10.1073/pnas.1802279115
AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipid us.
Ando, F.; Mori, S.; Yui, N.; Morimoto, T.; Nomura, N.; Sohara, E.; Rai, T.; Sasaki, S.; Kondo, Y.; Kagechika, H.; Uchida, S.
Nature Commun. 2018, 9, 1411. DOI: https://doi.org/10.1038/s41467-018-03771-2
Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models.
Shimada, S.; Akiyama, Y.; Mogushi, K.; Ishigami-Yuasa, M.; Kagechika, H.; Nagasaki, H.; Fukamachi, H.; Yuasa, Y.; Tanaka, S.
Br J Cancer 2018, 118 (7), 972-984. DOI: 10.1038/s41416-018-0008-y
Conformational Properties of Aromatic Oligoamides Bearing Pyrrole Rings.
Tojo, Y.; Urushibara, K.; Yamamoto, S.; Mori, H.; Masu, H.; Kudo, M.; Hirano, T.; Azumaya, I.; Kagechika, H.; Tanatani, A.
J. Org. Chem. 2018, 83, 4606-4617. DOI: 10.1021/acs.joc.8b00349
Unique properties of 1,5-naphthyridin-2(1H)-one derivatives as environmental-polarity-sensitive fluorescent dyes.
Yokoo, H.; Ohsaki, A.; Kagechika, H.; Hirano, T.
Eur. J. Org. Chem. 2018, 16, 679-687. DOI: https://doi.org/10.1002/ejoc.201701609
Novel YAP1 Activator, Identified by Transcription-Based Functional Screen, Limits Multiple Myeloma Growth.
Maruyama, J.; Inami, K.; Michishita, F.; Jiang, X. L.; Iwasa, H.; Nakagawa, K.; Ishigami-Yuasa, M.; Kagechika, H.; Miyamura, N.; Hirayama, J.; Nishina, H.; Nogawa, D.; Yamamoto, K.; Hata, Y.
Mol. Cancer Res. 2018, 16, 197-211. DOI: 10.1158/1541-7786.MCR-17-0382
Sucupiranins A-L, Furanocassane Diterpenoids from the Seeds of Bowdichia virgilioides.
Endo,Y.; Kasahara,T.; Harada,K.; Kubo, M.; Etoh, T.; Ishibashi, M.; Ishiyama, A.; Iwatsuki, M.; Otoguro, K.; Ohmura, S.; Akisue, G.; Hirano, T.; Kagechika, H.; Fukuyama, Y.; Ohsaki, A.
J. Nat. Prod 2017, 80, 3120-3127. DOI: 10.1021/acs.jnatprod.7b00249
Modulating Biocatalytic Activity toward Sterically Bulky Substrates in CO2-Expanded Biobased Liquids by Tuning the Physicochemical Properties.
Hoang, H. N.; Granero-Fernandez, E.; Yamada, S.; Mori, S.; Kagechika, H.; Medina-Gonzalez, Y.; Matsuda, T.
ACS Sus. Chem. Eng. 2017, 5, 11051-11059. DOI: 10.1021/acssuschemeng.7b03018
Crystal Engineering of N,N’-Diphenylurea Compounds Featuring Phenyl-Perfluorophenyl Interaction.
Yamasaki, R.; Iida, M.; Ito, A.; Fukuda, K.; Tanatani, A.; Kagechika, H., Masu, H. Okamoto, I.
Crystal Growth Des. 2017, 17, 5858-5866. DOI: 10.1021/acs.cgd.7b00951
Novel non-steroidal progesterone receptor ligands based on m-carborane containing a secondary alcohol: effect of chirality on ligand activity.
Mori, S.; Takagaki, R.; Fujii, S.; Urushibara, K.; Tanatani, A.; Kagechika, H.
Chem. Pharm. Bull. 2017, 65, 1051-1057. DOI: 10.1248/cpb.c17-00544
Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure.
Suzuki, D.; Saito-Hakoda, A.; Ito, R.; Shimizu, K.; Parvin, R.; Shimada, H.; Noro, E.; Suzuki, S.; Fujiwara, I.; Kagechika, H.; Rainey, W. E.; Kure, S.; Ito, S.; Yokoyama, A.; Sugawara, A.
Plos ONE 2017, 12, e0181055. DOI: 10.1371/journal.pone.0181055
Selective Reagent for Detection of N-ε-Monomethylation of a Peptide Lysine Residue through SNAr Reaction.
Mori, S.; Hirano T.; Takaguchi, A.; Fujiwara, T.; Okazaki, Y.; Kagechika, H.
Eur. J. Org. Chem. 2017, 25, 3606-3611. DOI: 10.1002/ejoc.201700488
Development of WNK signaling inhibitors as a new class of antihypertensive drugs. Bioorg.
Ishigami-Yuasa, M.; Watanabe, Y.; Mori, T.; Masuno, H.; Fujii, S.; Kikuchi, E.; Uchida, S.; Kagechika, H.
Med. Chem. 2017, 25, 3845-3852. DOI: 10.1016/j.bmc.2017.05.034
Drug-Repositioning Screening for Keap1-Nrf2 Binding Inhibitors using Fluorescence Correlation Spectroscopy.
Yoshizaki, Y.; Mori, T.; Ishigami-Yuasa, M.; Kikuchi, E.; Takahashi, D.; Zeniya, M.; Nomura, N.; Mori, Y.; Araki, Y.; Ando, F.; Mandai, S.; Kasagi, Y.; Arai, Y.; Sasaki, E.; Yoshida, S.; Kagechika, H.; Rai, T.; Uchida, S.; Sohara, E.
Sci. Rep. 2017, 7, 3945. DOI: 10.1038/s41598-017-04233-3
Development of nonsteroidal glucocorticoid receptor modulators based on N-benzyl-N-(4-phenoxyphenyl)benzenesulfonamide scaffold.
Yoshioka, H.; Yamada, A.; Nishiyama, Y.; Kagechika, H.; Hashimoto, Y.; Fujii, S.
Bioorg. Med. Chem. 2017, 25, 3461-3470. DOI: 10.1016/j.bmc.2017.04.032
Retinoid derivative Tp80 exhibits anti-hepatitis C virus activity through restoration of GI-GPx expression.
Nguyen, B. N.; Okuno, Y.; Ajiro, M.; Iida, K.; Denawa, M.; Yamamoto, M.; Sakamoto, N.; Kagechika, H.; Hagiwara, M.
J. Med. Virol. 2017, 89, 1224-1234. DOI: 10.1002/jmv.24739
CO2-expanded bio-based liquids as novel solvents for enantioselective biocatalysis.
Hoang, H. N.; Nagashima, Y.; Mori, S.; Kagechika, H.; Matsuda, T.
Tetrahedron 2017, 73, 2984-2989. DOI: 10.1016/j.tet.2017.04.024
9-cis Retinoic acid modulates myotrophin expression and its miR in physiological and pathophysiological cell models.
Perri, M.; Caroleo, Nannan M. C.; Gallelli, L. L.; De Sarro, G.; Kagechika, H.; Cione, E.
Exp. Cell Res. 2017, 354, 25-30. DOI: 10.1016/j.yexcr.2017.03.022
The receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.
Tsuji, M.; Shudo, K.; Kagechika, H.
FEBS Open Bio. 2017, 7, 391-396. DOI: 10.1002/2211-5463.12188
Down-regulation of histone deacetylase 4, -5 and -6 as a mechanism of synergistic enhancement of apoptosis in human lung cancer cells treated with the combination of a synthetic retinoid, Am80 and green tea catechin.
Oya, Y.; Mondal, A.; Rawangkan, A.; Umsumarng, S.; Iida, K.; Watanabe, T.; Kanno, M.; Suzuki, K.; Li, Z.; Kagechika, H.; Shudo, K.; Fujiki, H.; Suganuma, M.
J. Nutr. Biochem. 2017, 42, 7-16. DOI: 10.1016/j.jnutbio.2016.12.015
Identification of Cyproheptadine as an Inhibitor of SET Domain Containing Lysine Methyltransferase 7/9 (Set7/9) That Regulates Estrogen-Dependent Transcription.
Handa, N.; Umehara, T.; Sonoda, T.; Ogawa, K.; Tariq, M.; Nishino, N.; Dan, S.; Kagechika, H.; Yamori, T.; Yokoyama, S.; Yoshida, M.
J. Med. Chem. 2016, 59, 3650-3660. DOI: 10.1021/acs.jmedchem.5b01732
Development of an “OFF-ON-OFF” fluorescent pH sensor suitable for the study of intracellular pH.
Hirano, T.; Noji, Y.; Shiraishi, T.; Ishigami-Yuasa, M.; Kagechika, H.
Tetrahedron 2016, 72, 4925-4930. DOI: https://doi.org/10.1016/j.tet.2016.06.065
Validation of the chemical compound library screening for TAZ inhibitors by use of green fluorescence protein-fused TAZ.
Nagashima, S.; Maruyama, J.; Kawano, S.; Iwasa, H.; Nakagawa, K.; Ishigami-Yuasa, M.; Kagechika, H.; Nishina, H.; Hata, Y.
Cancer Sci. 2016, 107, 791-802. DOI: 10.1111/cas.12936
Steric structure?activity relationship of cyproheptadine derivatives as inhibitors of histone methyltransferase Set7/9.
Fujiwara, T.; Ohira, K.; Urushibara, K.; Ito, A.; Yoshida, M.; Kanai, M.; Tanatani, A.; Kagechika, H.; Hirano, T.
Bioorg. Med. Chem. 2016, 24, 4318-4323. DOI: 10.1016/j.bmc.2016.07.024
All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1 mediating ERK1/2 phosphorylation.
Persaud, S. D.; Park, S. W.; Ishigami-Yuasa, M.; Koyano-Nakagawa, N.;, Kagechika, H.; Wei, L.-N.
Sci. Rep. 2016, 6, 22396. DOI: 10.1038/srep22396
Two new diterpenoids from Salvia przewarskii.
Tsukada, H.; Kawabeb, H.; Ohtakac, A.; Saitod, Y.: Okamotoe, Y.: Torie, M.; Kagechika, H.; Hirotab, H.; Gongf, X.; Kurodac, C.; Ohsaki, A.
Nat. Prod. Commun. 2016, 11 (2), 135-272.
Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells.
Shrestha, R.; Tatsukawa, H.; Shrestha, R.; Ishibashi, N.; Matsuura, T.; Kagechika, H.; Kose, S.; Hitomi, K.; Imamoto, N.; Kojima, S.
Cell Death & Diseases 2015, 6, e2002. DOI: 10.1038/cddis.2015.339
Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression.
Saito-Hakoda, A.; Uruno, A.; Yokoyama, A.; Shimizu, K.; Parvin, R.; Kudo, M.; Saito-Ito, T.; Sato, I.; Kogure, N.; S uzuki, D.; Shimada, H.; Yoshikawa, T .; Fujiwara, I.; Kagechika, H.; Iwasaki, Y.; Kure, S.; Ito, S.; Sugawara, A.
Plos ONE 2015, 10, e0141960. DOI: 10.1371/journal.pone.0145286
A Modified Murine Embryonic Stem Cell Test for Evaluating the Teratogenic Effects of Drugs on Early Embryogenesis.
Yu. R.: Miyamura, N.; Okamoto-Uchida, Y.; Arima, N.; Ishigami-Yuasa, M.; Kagechika, H.; Nishina, H.
Plos ONE 2015, 10, e0145286. DOI: 10.1248/bpb.b18-00782
A cell-based screening for TAZ activators identifies ethacridine, a widely used antiseptic and ab ortifacient, as a compound that promotes dephosphorylation of TAZ and inhibits adipogenesis in C3H10T1/2 cells.
Kawano, S.; Maruyama, J.; Nagashima, S.; Inami, K.; Qiu, W.; Iwasa, H.; Nakagawa, K.; Ishigami-Yuasa, M.; Kagechika, H.; Nishina, H.; Hata, Y.J.
Biochem. 2015, 158, 413-420. DOI: 10.1093/jb/mvv051
6-Arylcoumarins: versatile scaffolds for fluorescent sensors.
Shiraishi, T.; Kagechika, H.; Hirano, T.*
New J. Chem. 2015, 39, 8389-8396. DOI: 10.1039/c5nj01609f
Docking simulations suggest that all-trans retinoic acid could bind to retinoid X receptors.
Tsuji, M.; Shudo, K.; Kagechika, H.
J. Comput. Aided Mol. Des. 2015, 29, 975-988. DOI: 10.1007/s10822-015-9869-9
A new cell-based assay to evaluate myogenesis in mouse myoblast C2C12 cells.
Kodaka, M.; Yang, Z.; Nakagawa, K.; Maruyama, J.; Xu, X.; Sarkar, A.; Ichimura, A.; Nasu, Y.; Ozawa, T.; Iwasa, H.; Ishigami-Yuasa, M.; Ito, S.; Kagechika, H.; Hata, Y.
Exp. Cell. Res. 2015, 336, 171-181. DOI: 10.1016/j.yexcr.2015.06.015
Carboxylic derivatives of vitamin K2 inhibit hepatocel lular carcinoma cell growth through caspase/transglutaminase-related signaling pathways.
Qin, X.-Y.; Fujii, S.; Shimizu, A.; Kagechika, H.; KOJIMA, S.
J. Nutr. Sci.Vitaminol. 2015, 61, 285-290. DOI: 10.3177/jnsv.61.285.
Design and synthesis of 4-benzyl-1-(2H)-phthalazinone derivatives as novel an drogen receptor antagonists.
Inoue, K.; Urushibara, K.; Kanai, M.; Yura, K.; Fujii, S.; Ishigami-Yuasa, M.; Hashimoto, Y.; Mori, S.; Kawachi, E.; Matsumura, M.; Hirano, T.; Kagechik, H.; Tanatani, A.
Eur. J. Med. Chem. 2015, 102, 310-319. DOI: 110.1016/j.ejmech.2015.08.002
Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters.
Nishiyama, S.; Urushibara, K.; Masu, H.; Azumaya, I.; Kagechika, H. Tanatani, A.
J. Am. Soc. Nephrol. 2015, 26, 1525-1536. DOI: 10.1681/ASN.2014060560.
Conformational and chiral properties of cyclic-tri(N-methyl-meta-benzamide) bearing amidino groups.
Inoue, K.; Urushibara, K.; Kanai, M.; Yura, K.; Fujii, S.; Ishigami-Yuasa, M.; Hashimoto, Y.; Mori, S.; Kawachi, E.; Matsumura, M.; Hirano, T.; Kagechik, H.; Tanatani, A.
Chirality 2015, 27, 487-491. DOI: 10.1002/chir.22476
Systematic synthesis and anti-inflammatory activity of ω-carboxylated menaquinone derivatives - Investigations on identified and putative vitamin K2 metabolites.
Fujii, S.; Shimizu, A.; Takeda, N.; Oguchi, K.; Katsurai, T.; Shirakawa, H.; Komai, M.; Kagechika, H.
Bioorg. Med. Chem. 2015, 23, 2344-2352. DOI: 10.1016/j.bmc.2015.03.070
Retinoic acid receptor signaling is required to maintain glucose-stimulated insulin secretion and b-cell mass.
Brun, P.-J.; Grijalva, A.; Rausch, R.; Watson, E.; Yuen, J. J.; Das, B. C.; Shudo, K.; Kagechika, H.; Leibel, R. L.; Blaner, W. S.
FASEB J. 2015, 29, 671-683. DOI: 10.1096/fj.14-256743
Development of 1,3-diphenyladamantane derivatives as nonstero idal progesterone receptor antagonists.
Mori, S.; Takeuchi, Y.; Tanatani, A.; Kagechika, H.; Fujii, S.
Bioorg. Med. Chem. 2015, 23, 803-809. DOI: 10.1016/j.bmc.2014.12.047