Natural Product (NP) Details

General Information of the NP (ID: NP1128)
Name
Rottlerin
Synonyms
rottlerin; Mallotoxin; 82-08-6; Kamalin; UNII-E29LP3ZMUH; E29LP3ZMUH; CHEMBL34241; CHEBI:8899; (E)-1-(6-((3-Acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl)-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-8-yl)-3-phenyl-2-propen-1-one; NSC56346; NSC94525; MFCD00017361; 1-[6-(3-Acetyl-2,4,6-trihydroxy-5-methyl-benzyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-3-phenyl-propenone; 1-[6-[(3-Acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2,2-dimethylchromen-8-yl]-3-phenylprop-2-en-1-one; (E)-1-(6-(3-acetyl-2,4,6-trihydroxy-5-methylbenzyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl)-3-phenylprop-2-en-1-one; SR-01000076106; 1-[6-[(3-Acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-8-yl]-3-phenyl-2-propen-1-one; EINECS 201-395-4; NSC 56346; NSC 94525; BRN 0070757; BMK1-F10; Rottlerin, 98%; R5648 (Rottlerin); BiomolKI_000058; BiomolKI2_000064; R 5648; Lopac0_001052; BSPBio_001080; (E)-1-[6-[(3-acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2,2-dimethylchromen-8-yl]-3-phenylprop-2-en-1-one; 5-18-05-00695 (Beilstein Handbook Reference); MLS003370622; SCHEMBL148175; GTPL2611; SCHEMBL1537089; BCBcMAP01_000019; CHEBI:92065; Rottlerin - CAS 82-08-6; DTXSID30231502; HMS1362F21; HMS1792F21; HMS1990F21; HMS3263C06; HMS3403F21; ZINC3874886; Tox21_501052; BDBM50126829; CCG-36482; LMPK12120428; NSC-56346; NSC-94525; AKOS024282482; LP01052; SDCCGSBI-0051022.P002; IDI1_002135; NCGC00025228-02; NCGC00025228-03; NCGC00025228-04; NCGC00025228-05; NCGC00025228-06; NCGC00025228-07; NCGC00025228-08; NCGC00025228-09; NCGC00025228-10; NCGC00025228-11; NCGC00025228-12; NCGC00025228-19; NCGC00261737-01; (2E)-1-[6-(3-acetyl-2,4,6-trihydroxy-5-methylbenzyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-3-phenylprop-2-en-1-one; Acetophenone, 3'-((8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl)-2',4',6'-trihydroxy-5'-methyl-; HY-18980; SMR000058242; ST056358; CS-0014823; EU-0101052; S7862; C10721; Q7370686; SR-01000076106-2; SR-01000076106-3; SR-01000076106-6; BRD-K03816923-001-03-9; BRD-K39256324-001-01-5; (E)-1-[6-[(3-acetyl-2,4,6-trihydroxy-5-methyl-phenyl)methyl]-5,7-dihydroxy-2,2-dimethyl-chromen-8-yl]-3-phenyl-prop-2-en-1-one; (E)-1-[6-[(3-Acetyl-2,4,6-trihydroxy-methylphenyl)methyl]-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-8-yl]-3-phenyl-2-propen-1-one; 1-(6-(3-acetyl-2,4,6-trihydroxy-5-methylbenzyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl)-3-phenylprop-2-en-1-one; 3'-((8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl)-2',4',6'-trihydroxy-5'-methyl-acetophenone; 3'-[(8-Cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-2',4',6'-trihydroxy-5'-methylacetophenone; 3-{[8-((2E)-3-phenylprop-2-enoyl)-5,7-dihydroxy-2,2-dimethyl(2H-chromen-6-yl)] methyl}-1-acetyl-2,4,6-trihydroxy-5-methylbenzene; 6-(3-Acetyl-2,4,6-trihydroxy-5-methylbenzyl)-2,2-dimethyl-8-(3-phenylpropenoyl)-2H-1-benzopyran-5,7-diol
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Species Origin Mallotus philippinensis ...     Click to Show/Hide
Mallotus philippinensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malpighiales
Family: Euphorbiaceae
Genus: Mallotus
Species: Mallotus philippinensis
Disease Parkinson's disease [ICD-11: 8A00] Preclinical [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.049
 
MDCK Permeability
 -4.736
 
PAMPA
 ++
 
HIA
 - - -
 
Distribution
VDss
 0.125
 
PPB
 98%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 +++
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 +++
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 +++
 
Excretion
CLplasma
 2.825
 
T1/2
 1.358
Toxicity
DILI
 -
 
Rat Oral Acute Toxicity
 - -
 
FDAMDD
 +
 
Respiratory
 +++
 
Human Hepatotoxicity
 +
 
Ototoxicity
 - -
 
Drug-induced Nephrotoxicity
 - -
 
Drug-induced Neurotoxicity
 - - -
 
Hematotoxicity
 - -
 
Genotoxicity
 +
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C30H28O8
PubChem CID
5281847
Canonical SMILES
CC1=C(C(=C(C(=C1O)C(=O)C)O)CC2=C(C(=C3C(=C2O)C=CC(O3)(C)C)C(=O)C=CC4=CC=CC=C4)O)O
InChI
1S/C30H28O8/c1-15-24(33)19(27(36)22(16(2)31)25(15)34)14-20-26(35)18-12-13-30(3,4)38-29(18)23(28(20)37)21(32)11-10-17-8-6-5-7-9-17/h5-13,33-37H,14H2,1-4H3/b11-10+
InChIKey
DEZFNHCVIZBHBI-ZHACJKMWSA-N
CAS Number
CAS 82-08-6
ChEBI ID
CHEBI:8899
Herb ID
HBIN042467
SymMap ID
SMIT17499
TTD Drug ID
D0R1JI
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 BIRC5  Molecule Info 
Pathway MAP
Down-regulation Expression XIAP  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
A-172 CVCL_0131 Glioblastoma Homo sapiens
T98 CVCL_B368 Glioblastoma Homo sapiens
U-251MG CVCL_0021 Astrocytoma Homo sapiens
                    Experimental
                    Result(s)		 Rottlerin sensitizes glioma cells to TRAIL-induced apoptosis by inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP.
          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
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Rottlerin synergistically enhances imatinib-induced apoptosis of BCR/ABL-expressing cells through its mitochondrial uncoupling effect independent of protein kinase C-delta.
          Sorafenib      Renal cell carcinoma     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
                    Experimental
                    Result(s)		 Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells.
Target and Pathway
Target(s) Protein kinase C (PRKC)  Molecule Info  [5]
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: 2611).
Reference 2 Rottlerin sensitizes glioma cells to TRAIL-induced apoptosis by inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP. Oncogene. 2005 Jan 27;24(5):838-49.
Reference 3 Rottlerin synergistically enhances imatinib-induced apoptosis of BCR/ABL-expressing cells through its mitochondrial uncoupling effect independent of protein kinase C-delta. Oncogene. 2007 May 10;26(21):2975-87.
Reference 4 Coadministration of sorafenib with rottlerin potently inhibits cell proliferation and migration in human malignant glioma cells. J Pharmacol Exp Ther. 2006 Dec;319(3):1070-80.
Reference 5 Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42.
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