Natural Product: NPC476806

Natural Product IDNPC476806
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(3R,3aR,4S,5aR,6R,9R,9bR)-9-formyl-6-hydroxy-3,5a-dimethyl-2-oxo-3,3a,4,5,6,7,8,9,9a,9b-decahydrobenzo[g][1]benzofuran-4-yl] 4-hydroxy-2-methylidenebutanoate
IUPAC Name [(3R,3aR,4S,5aR,6R,9R,9bR)-9-formyl-6-hydroxy-3,5a-dimethyl-2-oxo-3,3a,4,5,6,7,8,9,9a,9b-decahydrobenzo[g][1]benzofuran-4-yl] 4-hydroxy-2-methylidenebutanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44445514
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001543] Sesquiterpene lactones
            • [CHEMONTID:0001772] Eudesmanolides, secoeudesmanolides, and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey OWTWBLYOTMJQME-ZTNIVYPMSA-N
Standard InCHI InChI=1S/C20H28O7/c1-10(6-7-21)18(24)26-13-8-20(3)14(23)5-4-12(9-22)16(20)17-15(13)11(2)19(25)27-17/h9,11-17,21,23H,1,4-8H2,2-3H3/t11-,12+,13+,14-,15-,16?,17+,20+/m1/s1
SMILES C[C@@H]1[C@@H]2[C@H](C[C@]3([C@@H](CC[C@H](C3[C@H]2OC1=O)C=O)O)C)OC(=O)C(=C)CCO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   380.18 Volume:   379.793
?
Van der Waals volume.
Dense:   1.001 LogP:   1.0
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.339
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.371
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   110.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.416 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.978 Fsp3:   0.75
MCE-18:   57.829
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.495 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.255 Promiscuous compounds:   0.102

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.338 MDCK Permeability:   -5.076
Pgp-inhibitor:   0.067 Pgp-substrate:   0.309
PAMPA:   0.673
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.009
20% Bioavailability (F20%):   0.952 30% Bioavailability (F30%):   0.97
50% Bioavailability (F50%):   0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.198 MRP1:   0.752
Plasma Protein Binding (PPB):   54.426% Volume Distribution (VD):   -0.079
Fu: 47.735%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.003
BSEP inhibitor:   0.922

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.042 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.032
CYP3A4-inhibitor:   0.286 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.248
HLM stability:   0.495
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  5.86 Half-life (T1/2):  2.327

ADMET: Toxicity

hERG Blockers:  0.008 hERG Blockers (10um):  0.068
Human Hepatotoxicity (H-HT):  0.462 Drug-induced Liver Injury (DILI):  0.27
AMES Toxicity:  0.482 Rat Oral Acute Toxicity:  0.078
Maximum Recommended Daily Dose:  0.098 Skin Sensitization:  0.993
Carcinogencity:  0.692 Eye Corrosion:  0.472
Eye Irritation:  0.844 Respiratory Toxicity:  0.189
Drug-induced Neurotoxicity:  0.136 Ototoxicity:  0.57
Hematotoxicity:  0.446 Drug-induced Nephrotoxicity:  0.777
Genotoxicity:  0.757 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.064 Hek293 Cytotoxicity:  0.136
BCF:   0.388
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   2.998
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.452
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.829
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO10212 Centaurea pullata Species Asteraceae Eukaryota Aerial parts Chra Mountain in Blida (North Algeria) 2006-APR PMID[17979247]
NPO10212 Centaurea pullata Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[18280170]
NPO10212 Centaurea pullata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10212 Centaurea pullata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 0.2 ug/ml PMID[17979247]
NPT729 Organism Micrococcus luteus Micrococcus luteus MBC = 0.3 ug/ml PMID[17979247]
NPT21 Organism Aspergillus niger Aspergillus niger MIC = 0.2 ug/ml PMID[17979247]
NPT21 Organism Aspergillus niger Aspergillus niger MFC = 0.3 ug/ml PMID[17979247]
NPT3695 Organism Penicillium funiculosum Penicillium funiculosum MIC = 0.3 ug/ml PMID[17979247]
NPT3695 Organism Penicillium funiculosum Penicillium funiculosum MFC = 0.4 ug/ml PMID[17979247]
NPT6344 Organism Penicillium ochrochloron Penicillium ochrochloron MIC = 0.3 ug/ml PMID[17979247]
NPT6344 Organism Penicillium ochrochloron Penicillium ochrochloron MFC = 0.4 ug/ml PMID[17979247]
NPT4945 Organism Fusarium tricinctum Fusarium tricinctum MIC = 0.2 ug/ml PMID[17979247]
NPT4945 Organism Fusarium tricinctum Fusarium tricinctum MFC = 0.3 ug/ml PMID[17979247]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 0.2 ug/ml PMID[17979247]
NPT79 Organism Bacillus subtilis Bacillus subtilis MBC = 0.3 ug/ml PMID[17979247]
NPT3729 Organism Pseudomonas tolaasii Pseudomonas tolaasii MIC = 0.4 ug/ml PMID[17979247]
NPT3729 Organism Pseudomonas tolaasii Pseudomonas tolaasii MBC = 0.5 ug/ml PMID[17979247]
NPT3176 Organism Aspergillus ochraceus Aspergillus ochraceus MIC = 0.2 ug/ml PMID[17979247]
NPT3176 Organism Aspergillus ochraceus Aspergillus ochraceus MFC = 0.3 ug/ml PMID[17979247]
NPT962 Organism Alternaria alternata Alternaria alternata MIC = 0.2 ug/ml PMID[17979247]
NPT962 Organism Alternaria alternata Alternaria alternata MFC = 0.3 ug/ml PMID[17979247]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 0.4 ug/ml PMID[17979247]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MBC = 0.5 ug/ml PMID[17979247]
NPT19 Organism Escherichia coli Escherichia coli MIC = 0.4 ug/ml PMID[17979247]
NPT19 Organism Escherichia coli Escherichia coli MBC = 0.4 ug/ml PMID[17979247]
NPT185 Organism Aspergillus flavus Aspergillus flavus MIC = 0.2 ug/ml PMID[17979247]
NPT185 Organism Aspergillus flavus Aspergillus flavus MFC = 0.3 ug/ml PMID[17979247]
NPT2567 Organism Trichoderma viride Hypocrea rufa MIC = 0.3 ug/ml PMID[17979247]
NPT2567 Organism Trichoderma viride Hypocrea rufa MFC = 0.4 ug/ml PMID[17979247]
NPT3608 Organism Salmonella enteritidis Salmonella enterica subsp. enterica serovar Enteritidis MIC = 0.4 ug/ml PMID[17979247]
NPT3608 Organism Salmonella enteritidis Salmonella enterica subsp. enterica serovar Enteritidis MBC = 0.4 ug/ml PMID[17979247]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC476806 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC476807
0.6032 Remote Similarity NPC78966
0.6032 Remote Similarity NPC284732
0.5645 Remote Similarity NPC284518
0.5517 Remote Similarity NPC15091
0.5441 Remote Similarity NPC37628
0.5352 Remote Similarity NPC474243

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC476806 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data