Natural Product (NP) Details

General Information of the NP (ID: NP8435)
Name
Apicidin
Synonyms
CHEMBL430060; OSI-2040; Apicidin _120249; Acipidin; SCHEMBL147997; ChEMBL_275631; GTPL7495; DTXSID40274182; BDBM50238632; ZINC17654900; MCULE-8969470747; NCGC00165733-01; (3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-6-[(1-methoxyindol-3-yl)methyl]-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone; Q16829635; (6S,9S,12S,14aR)-6-((S)-sec-Butyl)-9-(1-methoxy-1H-indol-3-ylmethyl)-12-(6-oxo-octyl)-decahydro-4a,7,10,13-tetraaza-benzocyclododecene-5,8,11,14-tetraone
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Species Origin Fusarium sp. ...     Click to Show/Hide
Fusarium sp.
Kingdom: Fungi
Phylum: Ascomycota
Class: Sordariomycetes
Order: Hypocreales
Family: Nectriaceae
Genus: Fusarium
Species: Fusarium sp.
Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C34H49N5O6
PubChem CID
6918328
Canonical SMILES
CCC(C)C1C(=O)N2CCCCC2C(=O)NC(C(=O)NC(C(=O)N1)CC3=CN(C4=CC=CC=C43)OC)CCCCCC(=O)CC
InChI
1S/C34H49N5O6/c1-5-22(3)30-34(44)38-19-13-12-18-29(38)33(43)35-26(16-9-7-8-14-24(40)6-2)31(41)36-27(32(42)37-30)20-23-21-39(45-4)28-17-11-10-15-25(23)28/h10-11,15,17,21-22,26-27,29-30H,5-9,12-14,16,18-20H2,1-4H3,(H,35,43)(H,36,41)(H,37,42)/t22-,26-,27-,29+,30-/m0/s1
InChIKey
JWOGUUIOCYMBPV-GMFLJSBRSA-N
Herb ID
HBIN016406
SymMap ID
SMIT14327
TTD Drug ID
D0W1PV
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Combination of apicidin and TRAIL may be an effective strategy for treating TRAIL-resistant Bcr-Abl expressing CML cells.
          Imatinib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABL  Molecule Info 
Pathway MAP
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive human leukaemia cells by enhancing the activation of mitochondria-dependent caspase cascades.
          Doxorubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
                    In-vitro Model Huh-7 CVCL_0336 Adult hepatocellular carcinoma Homo sapiens
Hep 3B2.1-7 CVCL_0326 Childhood hepatocellular carcinoma Homo sapiens
                    In-vivo Model Huh7 and Hep3B cells with or without SULF1 expression (1*106) were suspended in PBS and inoculated subcutaneously into the right flanks of 4- to 6-week-old male BALB/c nu/nu nude mice (NCI/NIH).
                    Experimental
                    Result(s)		 The combination of doxorubicin with apicidin significantly increased the anti-tumor effect in the SULF1-expressing Huh7 and Hep3B cells as compared to either apicidin or doxorubicin alone, both in vitro and in vivo.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Gemcitabine      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Capan-1 CVCL_0237 Pancreatic ductal adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression.
Target and Pathway
Target(s) Histone deacetylase (HDAC)  Molecule Info  [6]
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7495).
Reference 2 Cotreatment with apicidin overcomes TRAIL resistance via inhibition of Bcr-Abl signaling pathway in K562 leukemia cells. Exp Cell Res. 2009 Jul 1;315(11):1809-18.
Reference 3 Apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive human leukaemia cells by enhancing the activation of mitochondria-dependent caspase cascades. Br J Haematol. 2004 Jan;124(2):166-78.
Reference 4 Additive effect of apicidin and doxorubicin in sulfatase 1 expressing hepatocellular carcinoma in vitro and in vivo. J Hepatol. 2009 Jun;50(6):1112-21.
Reference 5 Apicidin sensitizes pancreatic cancer cells to gemcitabine by epigenetically regulating MUC4 expression. Anticancer Res. 2014 Oct;34(10):5269-76.
Reference 6 Histone deacetylase inhibitors in cancer therapy: latest developments, trends and medicinal chemistry perspective. Anticancer Agents Med Chem. 2007 Sep;7(5):576-92.
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