Natural Product: NPC470755

Natural Product IDNPC470755
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Eupatoriopicrin
IUPAC Name [(3aR,4R,6Z,10E,11aR)-6,10-dimethyl-3-methylidene-2-oxo-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-4-yl] (E)-4-hydroxy-2-(hydroxymethyl)but-2-enoate
Synonyms Eupatoriopicrin; Eupatoriopicrine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL221283
PubChem CID 6917047
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:0001771] Germacranolides 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 VWJYWGYJIDQUEG-UWRPYMCXSA-N
Standard InCHI InChI=1S/C20H26O6/c1-12-5-4-6-13(2)10-17(26-20(24)15(11-22)7-8-21)18-14(3)19(23)25-16(18)9-12/h6-7,9,16-18,21-22H,3-5,8,10-11H2,1-2H3/b12-9+,13-6-,15-7+/t16-,17-,18+/m1/s1
SMILES OC/C=C(/C(=O)O[C@@H]1C/C(=CCC/C(=C/[C@@H]2[C@@H]1C(=C)C(=O)O2)/C)/C)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.17 Volume:   374.286
?
Van der Waals volume.
Dense:   0.968 LogP:   1.435
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.874
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.94
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   93.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.451 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.862 Fsp3:   0.5
MCE-18:   36.0
?
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:   0.06 Fluc inhibitor:   0.069
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.054
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.062
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.585 Promiscuous compounds:   0.442

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.804 MDCK Permeability:   -4.731
Pgp-inhibitor:   0.251 Pgp-substrate:   0.647
PAMPA:   0.827
?
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):   0.665
20% Bioavailability (F20%):   0.964 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.735
Plasma Protein Binding (PPB):   77.476% Volume Distribution (VD):   -0.306
Fu: 18.328%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.01
BSEP inhibitor:   0.749

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.307 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.007 CYP2D6-substrate:   0.012
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.476
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.729
HLM stability:   0.007
?
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):  8.021 Half-life (T1/2):  1.106

ADMET: Toxicity

hERG Blockers:  0.003 hERG Blockers (10um):  0.057
Human Hepatotoxicity (H-HT):  0.948 Drug-induced Liver Injury (DILI):  0.965
AMES Toxicity:  0.441 Rat Oral Acute Toxicity:  0.062
Maximum Recommended Daily Dose:  0.626 Skin Sensitization:  1.0
Carcinogencity:  0.811 Eye Corrosion:  0.011
Eye Irritation:  0.627 Respiratory Toxicity:  0.133
Drug-induced Neurotoxicity:  0.26 Ototoxicity:  0.562
Hematotoxicity:  0.723 Drug-induced Nephrotoxicity:  0.922
Genotoxicity:  0.757 RPMI-8226 Immunitoxicity:  0.139
A549 Cytotoxicity:  0.081 Hek293 Cytotoxicity:  0.227
BCF:   0.871
?
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:   3.743
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.554
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.76
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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
NPO33469 Asteraceae Family Asteraceae Eukaryota n.a. n.a. n.a. PMID[18329753]
NPO33469 Asteraceae Family Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT2716 Individual protein UDP-N-acetylglucosamine 1-carboxyvinyltransferase Escherichia coli K-12 IC50 = 32700.0 nM PMID[17417907]
NPT2717 Individual protein UDP-N-acetylglucosamine 1-carboxyvinyltransferase Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228) IC50 = 19800.0 nM PMID[26287401]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens ED50 = 3.3 umol/L PMID[17253862]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 5700.0 nM PMID[8350087]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC80 = 13.4 uM PMID[8350087]

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 NPC470755 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 NPC298801
0.7551 Intermediate Similarity NPC611318
0.7347 Intermediate Similarity NPC171204
0.7347 Intermediate Similarity NPC606745
0.7143 Intermediate Similarity NPC486031
0.7037 Intermediate Similarity NPC481909
0.7037 Intermediate Similarity NPC158756
0.7037 Intermediate Similarity NPC601035
0.7018 Intermediate Similarity NPC134725
0.7018 Intermediate Similarity NPC48657
0.6667 Remote Similarity NPC469910
0.6452 Remote Similarity NPC486033
0.6393 Remote Similarity NPC486037
0.6333 Remote Similarity NPC481911
0.6316 Remote Similarity NPC482126
0.623 Remote Similarity NPC288876
0.6207 Remote Similarity NPC482130
0.6207 Remote Similarity NPC482128
0.6207 Remote Similarity NPC482129
0.5833 Remote Similarity NPC482127
0.5833 Remote Similarity NPC269509
0.5789 Remote Similarity NPC116177
0.5763 Remote Similarity NPC482131
0.569 Remote Similarity NPC473390
0.5625 Remote Similarity NPC482132
0.5522 Remote Similarity NPC59330
0.5517 Remote Similarity NPC250940
0.5517 Remote Similarity NPC7563
0.5517 Remote Similarity NPC169575
0.5484 Remote Similarity NPC482133
0.5439 Remote Similarity NPC270126
0.541 Remote Similarity NPC488116
0.5385 Remote Similarity NPC96018
0.5333 Remote Similarity NPC488117
0.5323 Remote Similarity NPC131669
0.5273 Remote Similarity NPC97516
0.5273 Remote Similarity NPC167881
0.5273 Remote Similarity NPC98557
0.527 Remote Similarity NPC605837
0.5263 Remote Similarity NPC229825
0.5263 Remote Similarity NPC602858
0.5246 Remote Similarity NPC320630
0.5238 Remote Similarity NPC482134
0.5217 Remote Similarity NPC486030
0.5185 Remote Similarity NPC58956
0.5185 Remote Similarity NPC163003
0.5185 Remote Similarity NPC295633
0.5185 Remote Similarity NPC269206
0.5172 Remote Similarity NPC476028
0.5167 Remote Similarity NPC488296
0.5156 Remote Similarity NPC281005
0.5156 Remote Similarity NPC481910
0.5082 Remote Similarity NPC178702
0.5079 Remote Similarity NPC212486
0.507 Remote Similarity NPC486032

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470755 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