Natural Product (NP) Details

General Information of the NP (ID: NP4401)
Name
Brusatol
Synonyms
Brusatol; 14907-98-3; Yatansin; (+)-Brusatol; CHEBI:3197; CHEMBL459546; (11beta,12alpha,15beta)-13,20-Epoxy-3,11,12-trihydroxy-15-((3-methyl-1-oxo-2-butenyl)oxy)-2,16-dioxopicras-3-en-21-oic acid, methyl ester; NSC 172924; BRN 1444847; (1R,2S,3S,3aS,3a1R,4R,6aR,7aR,11aS,11bR)-Methyl 1,2,9-trihydroxy-8,11a-dimethyl-4-((3-methylbut-2-enoyl)oxy)-5,10-dioxo-2,3,3a,4,5,6a,7,7a,10,11,11a,11b-dodecahydro-1H-3,3a1-(epoxymethano)dibenzo[de,g]chromene-3-carboxylate; Methyl 13,20-epoxy-3,11,12-trihydroxy-15-((3-methyl-1-oxo-2-butenyl)oxy)-2,16-dioxopicras-3-en-21-oate (11beta,12alpha,15beta)-; SCHEMBL1276480; Brusatol, >=95% (HPLC); DTXSID70164163; QCR-223; BCP15272; BDBM50535743; MFCD01746220; ZINC30726694; AKOS016013415; CS-W019658; 2H-3,11c-beta-(Epoxymethano)phenanthro(10,1-bc)pyran-3-alpha(3a-beta-H)-carboxylic acid, 1,4,5,6a-beta,7,7a-alpha,10,11,11a,11b-alpha-decahydro-8,11a-beta-dimethyl-5,10-dioxo-1-beta,2-alpha,4-beta,9-tetrahydroxy-, methyl ester, 4-(3-methylcrotonate); AS-55977; HY-19543; Picras-3-en-21-oic acid, 13,20-epoxy-3,11,12-trihydroxy-15-((3-methyl-1-oxo-2-butenyl)oxy)-2,16-dioxo-, methyl ester, (11beta,12alpha,15beta)-; C08754; Q27105985; methyl trihydroxy-dimethyl-(3-methylbut-2-enoyloxy)-dioxo-[?]carboxylate; Picras-3-en-21-oicacid,13,20-epoxy-3,11,12-trihydroxy-15-[(3-methyl-1-oxo-2-buten-1-yl)oxy]-2,16-dioxo-,methyl ester, (11b,12a,15b)-
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Species Origin Brucea javanica ...     Click to Show/Hide
Brucea javanica
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Simaroubaceae
Genus: Brucea
Species: Brucea javanica
Disease Nasopharyngeal cancer [ICD-11: 2B6B] Investigative [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.78
 
MDCK Permeability
 -5.166
 
PAMPA
 ++
 
HIA
 - - -
 
Distribution
VDss
 -0.404
 
PPB
 61.8%
 
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
 3.294
 
T1/2
 2.67
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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Formula
C26H32O11
PubChem CID
73432
Canonical SMILES
CC1=C(C(=O)CC2(C1CC3C45C2C(C(C(C4C(C(=O)O3)OC(=O)C=C(C)C)(OC5)C(=O)OC)O)O)C)O
InChI
1S/C26H32O11/c1-10(2)6-15(28)37-18-20-25-9-35-26(20,23(33)34-5)21(31)17(30)19(25)24(4)8-13(27)16(29)11(3)12(24)7-14(25)36-22(18)32/h6,12,14,17-21,29-31H,7-9H2,1-5H3/t12-,14+,17+,18+,19+,20+,21-,24-,25+,26-/m0/s1
InChIKey
ZZZYHIMVKOHVIH-VILODJCFSA-N
CAS Number
CAS 14907-98-3
ChEBI ID
CHEBI:3197
Herb ID
HBIN018930
SymMap ID
SMIT00277
TCMSP ID
MOL008073
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin      Bladder 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		 Up-regulation Expression BAX  Molecule Info 
Pathway MAP
                    In-vitro Model CT26 CVCL_7254 Mouse colon adenocarcinoma Mus musculus
                    Experimental
                    Result(s)		 The combination of CDDP and BR was able to produce a synergistic antitumor effect in CRC cells, thus providing a solid foundation for further development of this combination regimen into an effective therapeutic method for CRC.
Target and Pathway
Target(s) Kelch-like ECH-associated protein 1 (KEAP1)  Molecule Info  [3]
Maleylacetoacetate isomerase (EIF5AL1)  Molecule Info  [4]
Nuclear factor erythroid 2-related factor 2 (Nrf2)  Molecule Info  [5]
Sequestosome-1 p62 (SQSTM1)  Molecule Info  [6]
KEGG Pathway Osteoclast differentiation Click to Show/Hide
2 Protein processing in endoplasmic reticulum
NetPath Pathway EGFR1 Signaling Pathway Click to Show/Hide
2 IL5 Signaling Pathway
Pathway Interaction Database IL1-mediated signaling events Click to Show/Hide
2 TNF receptor signaling pathway
3 p75(NTR)-mediated signaling
4 Neurotrophic factor-mediated Trk receptor signaling
Reactome NRIF signals cell death from the nucleus Click to Show/Hide
2 p75NTR recruits signalling complexes
3 NF-kB is activated and signals survival
4 Interleukin-1 signaling
WikiPathways Senescence and Autophagy in Cancer Click to Show/Hide
2 NRF2 pathway
3 Nuclear Receptors Meta-Pathway
4 Apoptosis-related network due to altered Notch3 in ovarian cancer
5 BDNF signaling pathway
6 RANKL/RANK Signaling Pathway
7 Signalling by NGF
8 IL-1 signaling pathway
9 Interleukin-1 signaling
10 Regulation of toll-like receptor signaling pathway
11 Oxidative Stress
12 Transcriptional activation by NRF2
13 Aryl Hydrocarbon Receptor Pathway
14 Mesodermal Commitment Pathway
15 Aryl Hydrocarbon Receptor
16 Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis
17 Arylhydrocarbon receptor (AhR) signaling pathway
References
Reference 1 Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway. Cancer Chemother Pharmacol. 2020 Jun;85(6):1097-1108.
Reference 2 Synergistic antitumor effect of brusatol combined with cisplatin on colorectal cancer cells. Int J Mol Med. 2018 Mar;41(3):1447-1454.
Reference 3 Resistance to gefitinib and cross-resistance to irreversible EGFR-TKIs mediated by disruption of the Keap1-Nrf2 pathway in human lung cancer cells. FASEB J. 2018 May 29:fj201800011R.
Reference 4 The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB J. 2019 Mar;33(3):3510-3522.
Reference 5 Free heme regulates placenta growth factor through NRF2-antioxidant response signaling. Free Radic Biol Med. 2019 Nov 1;143:300-308.
Reference 6 Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia. Theranostics. 2017 Apr 10;7(7):1890-1900.
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