Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma.

Abstract:

:This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase inhibitor (IC50 values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150× against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg po showed significant anti-inflammatory efficacy in HDM-induced allergic airway inflammation in mice, reducing inflammatory cell influx in the BALF and total IgE concentration in plasma, which correlated with decrease of chitinolytic activity. Therapeutic efficacy of compound 7f in the clinically relevant aeroallergen-induced acute asthma model in mice provides a rationale for developing AMCase inhibitor for the treatment of asthma.

journal_name

J Med Chem

authors

Mazur M,Olczak J,Olejniczak S,Koralewski R,Czestkowski W,Jedrzejczak A,Golab J,Dzwonek K,Dymek B,Sklepkiewicz PL,Zagozdzon A,Noonan T,Mahboubi K,Conway B,Sheeler R,Beckett P,Hungerford WM,Podjarny A,Mitschler A,Cous

doi

10.1021/acs.jmedchem.7b01051

subject

Has Abstract

pub_date

2018-02-08 00:00:00

pages

695-710

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

61

pub_type

杂志文章
  • Design, synthesis, and biological evaluation of new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives as CB2 selective agonists.

    abstract::On the basis of docking studies carried out using the recently published cannabinoid receptor models,35 new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB2 receptors. Compound 10, whic...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm0603466

    authors: Manera C,Benetti V,Castelli MP,Cavallini T,Lazzarotti S,Pibiri F,Saccomanni G,Tuccinardi T,Vannacci A,Martinelli A,Ferrarini PL

    更新日期:2006-10-05 00:00:00

  • Computer-assisted structure-activity studies of chemical carcinogens. Aromatic amines.

    abstract::Studies of molecular structure-carcinogenicity relations for a set of 157 aromatic amines are reported. A computer-assisted approach using pattern-recognition methods was used to develop a series of discriminants for aromatic amino carcinogenic potential. The 157 compounds were divided into subsets according to tumor ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00135a003

    authors: Yuta K,Jurs PC

    更新日期:1981-03-01 00:00:00

  • Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization Inhibitors Targeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy.

    abstract::We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compou...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.7b01858

    authors: Banerjee S,Arnst KE,Wang Y,Kumar G,Deng S,Yang L,Li GB,Yang J,White SW,Li W,Miller DD

    更新日期:2018-02-22 00:00:00

  • Chemogenomic Profiling of Human and Microbial FK506-Binding Proteins.

    abstract::FK506-binding proteins (FKBPs) are evolutionarily conserved proteins that display peptidyl-prolyl isomerase activities and act as coreceptors for immunosuppressants. Microbial macrophage-infectivity-potentiator (Mip)-type FKBPs can enhance infectivity. However, developing druglike ligands for FKBPs or Mips has proven ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.8b00137

    authors: Pomplun S,Sippel C,Hähle A,Tay D,Shima K,Klages A,Ünal CM,Rieß B,Toh HT,Hansen G,Yoon HS,Bracher A,Preiser P,Rupp J,Steinert M,Hausch F

    更新日期:2018-04-26 00:00:00

  • Proline-Based Allosteric Inhibitors of Zika and Dengue Virus NS2B/NS3 Proteases.

    abstract::The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.9b01697

    authors: Millies B,von Hammerstein F,Gellert A,Hammerschmidt S,Barthels F,Göppel U,Immerheiser M,Elgner F,Jung N,Basic M,Kersten C,Kiefer W,Bodem J,Hildt E,Windbergs M,Hellmich UA,Schirmeister T

    更新日期:2019-12-26 00:00:00

  • Anti-HIV agents that selectively target retroviral nucleocapsid protein zinc fingers without affecting cellular zinc finger proteins.

    abstract::Agents that target the two highly conserved Zn fingers of the human immunodeficiency virus (HIV) nucleocapsid p7 (NCp7) protein are under development as antivirals. These agents covalently modify Zn-coordinating cysteine thiolates of the fingers, causing Zn ejection, loss of native protein structure and nucleic acid b...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm9708543

    authors: Huang M,Maynard A,Turpin JA,Graham L,Janini GM,Covell DG,Rice WG

    更新日期:1998-04-23 00:00:00

  • Optimization of Potent ATAD2 and CECR2 Bromodomain Inhibitors with an Atypical Binding Mode.

    abstract::Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to no...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00021

    authors: Lucas SCC,Atkinson SJ,Bamborough P,Barnett H,Chung CW,Gordon L,Mitchell DJ,Phillipou A,Prinjha RK,Sheppard RJ,Tomkinson NCO,Watson RJ,Demont EH

    更新日期:2020-05-28 00:00:00

  • Synthesis and biological evaluations of certain 2-halo-2'-substituted derivatives of 9-beta-D-arabinofuranosyladenine.

    abstract::The synthesis of a series of 2-chloro- or 2-fluoro-9-(2-substituted-2-deoxy-beta-D-arabinofuranosyl)adenines (4g-n) is described. New compounds were prepared from either 2-chloroadenosine or 2-fluoroadenosine by first blocking the 3'- and 5'-hydroxyls as the tetraisopropyldisiloxane derivatives. Activation of O-2' by ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00397a024

    authors: Secrist JA 3rd,Shortnacy AT,Montgomery JA

    更新日期:1988-02-01 00:00:00

  • Synthesis and carbonic anhydrase isoenzymes I, II, IX, and XII inhibitory effects of dimethoxybromophenol derivatives incorporating cyclopropane moieties.

    abstract::Cyclopropylcarboxylic acids and esters and cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- and trans-esters 5 and 6 were obtained from the reaction of 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which afte...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm501573b

    authors: Boztaş M,Çetinkaya Y,Topal M,Gülçin İ,Menzek A,Şahin E,Tanc M,Supuran CT

    更新日期:2015-01-22 00:00:00

  • Immuno-suppressive effect of blocking the CD28 signaling pathway in T-cells by an active component of Echinacea found by a novel pharmaceutical screening method.

    abstract::AFTIR (after flowing through immobilized receptor) is a novel method for screening herbal extracts for pharmaceutical properties. Using AFTIR, we identified Cynarin in Echinacea purpurea by its selective binding to chip immobilized CD28, a receptor of T-cells, which is instrumental to immune functioning. The results o...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm0509039

    authors: Dong GC,Chuang PH,Forrest MD,Lin YC,Chen HM

    更新日期:2006-03-23 00:00:00

  • Structure-based exploration of cyclic dipeptide chitinase inhibitors.

    abstract::Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhi...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm049940a

    authors: Houston DR,Synstad B,Eijsink VG,Stark MJ,Eggleston IM,van Aalten DM

    更新日期:2004-11-04 00:00:00

  • Design and Synthesis of an Investigational Nonapeptide KISS1 Receptor (KISS1R) Agonist, Ac-d-Tyr-Hydroxyproline (Hyp)-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2 (TAK-448), with Highly Potent Testosterone-Suppressive Activity and Excellent Water Solubility.

    abstract::Metastin/kisspeptin is an endogenous ligand of KISS1 Receptor (KISS1R). Metastin and KISS1R are suggested to play crucial roles in regulating the secretion of gonadotropin-releasing hormone (GnRH), and continuous administration of metastin derivatives attenuated the plasma testosterone levels in male rats. Our optimiz...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.6b00379

    authors: Nishizawa N,Takatsu Y,Kumano S,Kiba A,Ban J,Tsutsumi S,Matsui H,Matsumoto SI,Yamaguchi M,Ikeda Y,Kusaka M,Ohtaki T,Itoh F,Asami T

    更新日期:2016-10-13 00:00:00

  • Structure-activity studies of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles: inhibitors of picornavirus uncoating.

    abstract::A series of substituted phenyl analogues of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes. Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound. Many of these ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00385a021

    authors: Diana GD,Oglesby RC,Akullian V,Carabateas PM,Cutcliffe D,Mallamo JP,Otto MJ,McKinlay MA,Maliski EG,Michalec SJ

    更新日期:1987-02-01 00:00:00

  • Design, synthesis, and biological evaluation of ellipticine-estradiol conjugates.

    abstract::Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm9602930

    authors: Devraj R,Barrett JF,Fernandez JA,Katzenellenbogen JA,Cushman M

    更新日期:1996-08-16 00:00:00

  • N-Substituted Quinolinonyl Diketo Acid Derivatives as HIV Integrase Strand Transfer Inhibitors and Their Activity against RNase H Function of Reverse Transcriptase.

    abstract::Bifunctional quinolinonyl DKA derivatives were first described as nonselective inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions of HIV-1 integrase (IN), while 7-aminosubstituted quinolinonyl derivatives were proven IN strand transfer inhibitors (INSTIs) that also displayed activity against ribonuc...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.5b00159

    authors: Pescatori L,Métifiot M,Chung S,Masoaka T,Cuzzucoli Crucitti G,Messore A,Pupo G,Madia VN,Saccoliti F,Scipione L,Tortorella S,Di Leva FS,Cosconati S,Marinelli L,Novellino E,Le Grice SF,Pommier Y,Marchand C,Costi R,Di

    更新日期:2015-06-11 00:00:00

  • Discovery and Structural Optimization of N5-Substituted 6,7-Dioxo-6,7-dihydropteridines as Potent and Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors against L858R/T790M Resistance Mutation.

    abstract::EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, the EGFR T790M secondary mutation has become a leading cause of clinically acquired resistance to these agents. Herein, on the basis of the previously reported irreversible EGFR i...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.6b00403

    authors: Hao Y,Wang X,Zhang T,Sun D,Tong Y,Xu Y,Chen H,Tong L,Zhu L,Zhao Z,Chen Z,Ding J,Xie H,Xu Y,Li H

    更新日期:2016-08-11 00:00:00

  • Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines.

    abstract::Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00401a014

    authors: Krapcho J,Turk C,Cushman DW,Powell JR,DeForrest JM,Spitzmiller ER,Karanewsky DS,Duggan M,Rovnyak G,Schwartz J

    更新日期:1988-06-01 00:00:00

  • Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics.

    abstract::Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm049614v

    authors: Boger DL,Miyauchi H,Du W,Hardouin C,Fecik RA,Cheng H,Hwang I,Hedrick MP,Leung D,Acevedo O,Guimarães CR,Jorgensen WL,Cravatt BF

    更新日期:2005-03-24 00:00:00

  • Toward a pharmacophore for kinase frequent hitters.

    abstract::Small molecule protein kinase inhibitors are widely employed as biological reagents and as leads in the design of drugs for a variety of diseases. One of the hardest challenges in kinase inhibitor design is achieving target selectivity. By utilizing X-ray structural information for four promiscuous inhibitors, we prop...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm049793g

    authors: Aronov AM,Murcko MA

    更新日期:2004-11-04 00:00:00

  • Novel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents.

    abstract::Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm1012006

    authors: Kumar K,Awasthi D,Lee SY,Zanardi I,Ruzsicska B,Knudson S,Tonge PJ,Slayden RA,Ojima I

    更新日期:2011-01-13 00:00:00

  • Potential inhibitors of L-asparagine biosynthesis. 2. Chemistry and biological activity of beta-hydroxyaspartic acid and its derivatives.

    abstract::Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-er...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00238a006

    authors: Mokotoff M,Bagaglio JF,Parikh BS

    更新日期:1975-04-01 00:00:00

  • Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates.

    abstract::A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibac...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00113a026

    authors: Albrecht HA,Beskid G,Christenson JG,Georgopapadakou NH,Keith DD,Konzelmann FM,Pruess DL,Rossman PL,Wei CC

    更新日期:1991-09-01 00:00:00

  • Pharmacology on rat ileum of certain 2-substituted 3-(dimethylamino)-5,6-dimethoxyindenes related to 5,6-(methylenedioxy)indene calcium antagonists.

    abstract::Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00210a028

    authors: Witiak DT,Kakodkar SV,Brunst GE,Baldwin JR,Rahwan RG

    更新日期:1978-12-01 00:00:00

  • Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization: evaluation of in vitro and in vivo anticancer activity.

    abstract::Biphenyl-4-carboxylic acid-[2-(1H-indol-3-yl)-ethyl]-methylamide 1 (CA224) is a nonplanar analogue of fascaplysin (2) that specifically inhibits Cdk4-cyclin D1 in vitro. Compound 1 blocks the growth of cancer cells at G0/G1 phase of the cell cycle. It also blocks the cell cycle at G2/M phase, which is explained by the...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm5014743

    authors: Mahale S,Bharate SB,Manda S,Joshi P,Bharate SS,Jenkins PR,Vishwakarma RA,Chaudhuri B

    更新日期:2014-11-26 00:00:00

  • Synthesis, characterization, and Ca2+ antagonistic activity of diltiazem metabolites.

    abstract::Diltiazem is a calcium antagonist widely used in the treatment of angina and hypertension. The contributions of metabolites of diltiazem to the vasorelaxant effects of diltiazem were investigated. The synthesis and spectroscopic characterization of eight major cis-diltiazem metabolites are described. Three of the comp...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00095a022

    authors: Li R,Farmer PS,Xie M,Quilliam MA,Pleasance S,Howlett SE,Yeung PK

    更新日期:1992-08-21 00:00:00

  • Intramolecular hydrogen bonding in medicinal chemistry.

    abstract::The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we de...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm100087s

    authors: Kuhn B,Mohr P,Stahl M

    更新日期:2010-03-25 00:00:00

  • Thiazolopyridine ureas as novel antitubercular agents acting through inhibition of DNA Gyrase B.

    abstract::A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration o...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm401268f

    authors: Kale MG,Raichurkar A,P SH,Waterson D,McKinney D,Manjunatha MR,Kranthi U,Koushik K,Jena Lk,Shinde V,Rudrapatna S,Barde S,Humnabadkar V,Madhavapeddi P,Basavarajappa H,Ghosh A,Ramya VK,Guptha S,Sharma S,Vachaspati P,

    更新日期:2013-11-14 00:00:00

  • Antipsoriatic anthrones with modulated redox properties. 2. Novel derivatives of chrysarobin and isochrysarobin--antiproliferative activity and 5-lipoxygenase inhibition.

    abstract::A novel series of 2- and 3-substituted 1,8-dihydroxy-9(10H)-anthracenones were synthesized and tested for their inhibitory activity against 5-lipoxygenase (5-LO) in bovine polymorphonuclear leukocytes and the growth of human keratinocytes. Structure-activity relationships are discussed with respect to the following re...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00037a017

    authors: Müller K,Leukel P,Ziereis K,Gawlik I

    更新日期:1994-05-27 00:00:00

  • Probing the anticancer activity of nucleoside analogues: a QSAR model approach using an internally consistent training set.

    abstract::The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsew...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm061445m

    authors: Helguera AM,Rodríguez-Borges JE,García-Mera X,Fernández F,Cordeiro MN

    更新日期:2007-04-05 00:00:00

  • Indolyl Azaspiroketal Mannich Bases Are Potent Antimycobacterial Agents with Selective Membrane Permeabilizing Effects and in Vivo Activity.

    abstract::The inclusion of an azaspiroketal Mannich base in the membrane targeting antitubercular 6-methoxy-1- n-octyl-1 H-indole scaffold resulted in analogs with improved selectivity and submicromolar activity against Mycobacterium tuberculosis H37Rv. The potency enhancing properties of the spiro-fused ring motif was affirmed...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.8b00777

    authors: Nyantakyi SA,Li M,Gopal P,Zimmerman M,Dartois V,Gengenbacher M,Dick T,Go ML

    更新日期:2018-07-12 00:00:00