Target Validation Information
Target ID T63816
Target Name Histone deacetylase 4
Target Type
Clinical Trial
Drug Potency against Target Cyclostellettamine derivative Drug Info IC50 = 17000 nM [527058]
AZUMAMIDE E Drug Info IC50 = 2280 nM [529411]
7-(Biphenyl-4-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info IC50 = 1100 nM [526871]
7-mercapto-N-(4-phenylthiazol-2-yl)heptanamide Drug Info IC50 = 32 nM [529093]
LARGAZOLE Drug Info IC50 = 3000 nM [530933]
Cyclo(-L-Am7(S2Py)-Aib-L-Ser-D-Pro-) Drug Info IC50 = 4 nM [529054]
ST-3050 Drug Info IC50 = 16100 nM [530016]
Octanedioic acid hydroxyamide pyridin-2-ylamide Drug Info IC50 = 248 nM [526266]
7-Mercapto-heptanoic acid pyridin-3-ylamide Drug Info IC50 = 110 nM [527439]
6-benzenesulfinylhexanoic acid hydroxamide Drug Info IC50 = 60 nM [527980]
N-Hydroxy-4-(3-phenyl-propionylamino)-benzamide Drug Info IC50 = 110 nM [527691]
7-(Biphenyl-4-yloxy)-1,1,1-trifluoro-heptan-2-one Drug Info IC50 = 2600 nM [526878]
N-Hydroxy-4-(4-phenyl-butyrylamino)-benzamide Drug Info IC50 = 44 nM [527691]
PSAMMAPLIN A Drug Info IC50 = 4 nM [526878]
2,2-bis(3-fluorophenyl)-N-hydroxyacetamide Drug Info IC50 = 700 nM [530327]
N-(2-Mercapto-ethyl)-N'-phenyl-succinamide Drug Info IC50 = 12500 nM [527500]
8-Mercapto-octanoic acid phenylamide Drug Info IC50 = 1500 nM [527439]
N-Hydroxy-4-((R)-2-phenyl-butyrylamino)-benzamide Drug Info IC50 = 68 nM [527691]
4-Hydroxy-N-(5-hydroxycarbamoyl-pentyl)-benzamide Drug Info IC50 = 149 nM [526266]
N-(6-Hydroxycarbamoyl-hexyl)-benzamide Drug Info IC50 = 568 nM [526266]
N-hydroxy-2,2-diphenylpropanamide Drug Info IC50 = 4500 nM [530327]
ST-2987 Drug Info IC50 = 2040 nM [530016]
7-Mercapto-heptanoic acid quinolin-3-ylamide Drug Info IC50 = 72 nM [527439]
N-(2-Mercapto-ethyl)-N'-phenyl-oxalamide Drug Info IC50 = 2800 nM [527500]
5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione Drug Info IC50 = 450 nM [529333]
7-Mercapto-heptanoic acid benzothiazol-2-ylamide Drug Info IC50 = 340 nM [527439]
N-Hydroxy-4-phenylacetylamino-benzamide Drug Info IC50 = 157 nM [527691]
7-(Biphenyl-3-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info IC50 = 620 nM [526871]
5-(4-Chloro-phenyl)-pentanoic acid hydroxyamide Drug Info IC50 = 2580 nM [527056]
7-(Naphthalen-2-yloxy)-1-oxazol-2-yl-heptan-1-one Drug Info IC50 = 520 nM [526871]
6-Mercapto-hexanoic acid phenylamide Drug Info IC50 = 370 nM [527439]
8-Oxo-8-phenyl-octanoic acid Drug Info IC50 = 270 nM [526266]
4-Benzoylamino-N-hydroxy-benzamide Drug Info IC50 = 210 nM [527691]
Romidepsin Drug Info IC50 = 1 nM [536272]
AZUMAMIDE B Drug Info IC50 = 3660 nM [529411]
6-phenylsulfanylhexanoic acid hydroxamide Drug Info IC50 = 120 nM [527980]
6-Phenoxy-hexane-1-thiol Drug Info IC50 = 11000 nM [527439]
2-(methylsulfonylthio)ethyl 2-propylpentanoate Drug Info IC50 = 9600 nM [529333]
N-hydroxy-9,10-dihydroanthracene-9-carboxamide Drug Info IC50 = 2320 nM [530327]
2,2-bis(4-chlorophenyl)-N-hydroxyacetamide Drug Info IC50 = 960 nM [530327]
Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Tic-) Drug Info IC50 = 4.2 nM [529054]
Cyclo(-L-Am7(S2Py)-L-2MePhe-L-Ala-D-Pro-) Drug Info IC50 = 2.2 nM [529054]
Cyclo(-L-Am7(S2Py)-Aib-L-Ph4-D-Pro-) Drug Info IC50 = 3.2 nM [529054]
Cyclo(-L-Am7(S2Py)-L-A1in-L-Ala-D-Pro-) Drug Info IC50 = 25 nM [529054]
N-hydroxy-2,2-diphenylacetamide Drug Info IC50 = 750 nM [530327]
N-hydroxy-9H-xanthene-9-carboxamide Drug Info IC50 = 250 nM [530327]
4-Dimethylamino-N-(6-mercapto-hexyl)-benzamide Drug Info IC50 = 610 nM [527439]
N-Hydroxy-4-(phenylacetylamino-methyl)-benzamide Drug Info IC50 = 2500 nM [526922]
(E)-8-Biphenyl-4-yl-1-oxazol-2-yl-oct-7-en-1-one Drug Info IC50 = 990 nM [526871]
N-Hydroxy-4-(5-phenyl-pentanoylamino)-benzamide Drug Info IC50 = 250 nM [527691]
AZUMAMIDE C Drug Info IC50 = 3160 nM [529411]
4-Chloro-N-(5-hydroxycarbamoyl-pentyl)-benzamide Drug Info IC50 = 369 nM [526878]
4-Butyrylamino-N-hydroxy-benzamide Drug Info IC50 = 1500 nM [526922]
Cyclo(-L-Am7(S2Py)-Aib-L-Ser(Bzl)-D-Pro-) Drug Info IC50 = 1.6 nM [529054]
N-(6-Mercapto-hexyl)-benzamide Drug Info IC50 = 360 nM [527439]
5-Mercapto-pentanoic acid phenylamide Drug Info IC50 = 6200 nM [527439]
N-Hydroxy-4-((S)-2-phenyl-butyrylamino)-benzamide Drug Info IC50 = 34 nM [527691]
N-(5-Hydroxycarbamoyl-pentyl)-4-nitro-benzamide Drug Info IC50 = 1566 nM [526878]
8-(Biphenyl-4-yloxy)-1,1,1-trifluoro-octan-2-one Drug Info IC50 = 2900 nM [526871]
9,9,9-Trifluoro-8-oxo-nonanoic acid phenylamide Drug Info IC50 = 6700 nM [526878]
N-Hydroxy-4-(2-phenyl-butyrylamino)-benzamide Drug Info IC50 = 54 nM [527691]
Octanedioic acid hydroxyamide pyridin-4-ylamide Drug Info IC50 = 306 nM [526266]
Octanedioic acid bis-hydroxyamide Drug Info IC50 = 1150 nM [526376]
Cyclo(-L-Am7(S2Py)-Aib-L-Phe-D-Pro-) Drug Info IC50 = 1.8 nM [529054]
Cyclo(-L-Am7(S2Py)-Aib-L-Ph5-D-Pro-) Drug Info IC50 = 2.7 nM [529054]
Cyclo(-L-Am7(S2Py)-Aib-L-Phg-D-Pro-) Drug Info IC50 = 56 nM [529054]
Cyclo(-L-Am7(S2Py)-Aib-L-Ala-D-Pro-) Drug Info IC50 = 5.2 nM [529054]
Cyclo(-L-Am7(S2Py)-D-2MePhe-L-Ala-D-Pro-) Drug Info IC50 = 70 nM [529054]
2,2-bis(4-fluorophenyl)-N-hydroxyacetamide Drug Info IC50 = 1100 nM [530327]
6-benzenesulfonylhexanoic acid hydroxamide Drug Info IC50 = 40 nM [527980]
Cyclo(-L-Am7(S2Py)-A2in-L-Ala-D-Pro-) Drug Info IC50 = 1.6 nM [529054]
7-Mercapto-heptanoic acid biphenyl-3-ylamide Drug Info IC50 = 75 nM [527439]
7-Mercapto-heptanoic acid biphenyl-4-ylamide Drug Info IC50 = 1100 nM [527439]
N-Hydroxy-4-(pentanoylamino-methyl)-benzamide Drug Info IC50 = 3600 nM [526922]
Cyclo(-L-Am7(S2Py)-D-A1in-L-Ala-D-Pro-) Drug Info IC50 = 2.4 nM [529054]
Action against Disease Model Romidepsin Inhibitors of histone deacetylase (HDAC) de-repress genes that subsequently result in growth inhibition, differentiation and apoptosis of cancer cells. Vorinostat (SAHA), romidepsin (depsipeptide, FK-228), belinostat (PXD101) and LAQ824/LBH589 have demonstrated therapeutic benefit as monotherapy in cutaneous T-cell lymphoma (CTCL) and have also demonstrated some therapeutic benefit in other malignancies. [552699] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations HDAC4 siRNAs are antiproliferative in t uMor cells;Loss of HDAC4 is well tolerated in normal cells Growth of normal murine embryonic fibroblasts from HDAC4 knockout mice is not affected by HDAC4 loss;Loss of HDAC4 leads to cell cycle arrest and apoptosis i [552699]
References
Ref 552699HDAC inhibitors: clinical update and mechanism-based potential. Biochem Pharmacol. 2007 Sep 1;74(5):659-71. Epub 2007 Apr 7.
Ref 527058Bioorg Med Chem Lett. 2004 May 17;14(10):2617-20.Three new cyclostellettamines, which inhibit histone deacetylase, from a marine sponge of the genus Xestospongia.
Ref 529411Bioorg Med Chem Lett. 2008 May 1;18(9):2982-4. Epub 2008 Mar 21.Evaluation of antiangiogenic activity of azumamides by the in vitro vascular organization model using mouse induced pluripotent stem (iPS) cells.
Ref 526871Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase.
Ref 529093J Med Chem. 2007 Nov 1;50(22):5425-38. Epub 2007 Oct 11.Design, synthesis, structure--selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors.
Ref 530933J Med Chem. 2010 Jun 24;53(12):4654-67.Synthesis and biological characterization of the histone deacetylase inhibitor largazole and C7- modified analogues.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 530016Bioorg Med Chem Lett. 2009 Apr 15;19(8):2346-9. Epub 2009 Feb 12.N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase [correction of deacetilase] (HDAC)inhibitors.
Ref 526266J Med Chem. 2002 Feb 14;45(4):753-7.Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 527980J Med Chem. 2006 Jan 26;49(2):800-5.Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 526878J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 526878J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors.
Ref 530327Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
Ref 527500Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 526266J Med Chem. 2002 Feb 14;45(4):753-7.Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.
Ref 526266J Med Chem. 2002 Feb 14;45(4):753-7.Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.
Ref 530327Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
Ref 530016Bioorg Med Chem Lett. 2009 Apr 15;19(8):2346-9. Epub 2009 Feb 12.N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase [correction of deacetilase] (HDAC)inhibitors.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 527500Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72.Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors.
Ref 529333Bioorg Med Chem Lett. 2008 Mar 15;18(6):1893-7. Epub 2008 Feb 8.New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 526871Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase.
Ref 527056Bioorg Med Chem Lett. 2004 May 17;14(10):2477-81.Stereodefined and polyunsaturated inhibitors of histone deacetylase based on (2E,4E)-5-arylpenta-2,4-dienoic acid hydroxyamides.
Ref 526871Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 526266J Med Chem. 2002 Feb 14;45(4):753-7.Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 536272Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006 Sep;5(9):769-84.
Ref 529411Bioorg Med Chem Lett. 2008 May 1;18(9):2982-4. Epub 2008 Mar 21.Evaluation of antiangiogenic activity of azumamides by the in vitro vascular organization model using mouse induced pluripotent stem (iPS) cells.
Ref 527980J Med Chem. 2006 Jan 26;49(2):800-5.Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 529333Bioorg Med Chem Lett. 2008 Mar 15;18(6):1893-7. Epub 2008 Feb 8.New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity.
Ref 530327Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
Ref 530327Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 530327Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
Ref 530327Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 526922J Med Chem. 2004 Jan 15;47(2):467-74.Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors.
Ref 526871Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 529411Bioorg Med Chem Lett. 2008 May 1;18(9):2982-4. Epub 2008 Mar 21.Evaluation of antiangiogenic activity of azumamides by the in vitro vascular organization model using mouse induced pluripotent stem (iPS) cells.
Ref 526878J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors.
Ref 526922J Med Chem. 2004 Jan 15;47(2):467-74.Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 526878J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors.
Ref 526871Bioorg Med Chem Lett. 2003 Nov 17;13(22):3909-13.Heterocyclic ketones as inhibitors of histone deacetylase.
Ref 526878J Med Chem. 2003 Nov 20;46(24):5097-116.Histone deacetylase inhibitors.
Ref 527691J Med Chem. 2005 Aug 25;48(17):5530-5.Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors.
Ref 526266J Med Chem. 2002 Feb 14;45(4):753-7.Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.
Ref 526376J Med Chem. 2002 Jul 18;45(15):3296-309.Structure-activity relationships on phenylalanine-containing inhibitors of histone deacetylase: in vitro enzyme inhibition, induction of differentiation, and inhibition of proliferation in Friend leukemic cells.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 530327Bioorg Med Chem Lett. 2009 Oct 1;19(19):5684-8. Epub 2009 Aug 7.Diphenylmethylene hydroxamic acids as selective class IIa histone deacetylase inhibitors.
Ref 527980J Med Chem. 2006 Jan 26;49(2):800-5.Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 527439J Med Chem. 2005 Feb 24;48(4):1019-32.Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates.
Ref 526922J Med Chem. 2004 Jan 15;47(2):467-74.Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors.
Ref 529054Bioorg Med Chem. 2007 Dec 15;15(24):7830-9. Epub 2007 Aug 26.Molecular design of histone deacetylase inhibitors by aromatic ring shifting in chlamydocin framework.

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