Natural Product: NPC118423

Natural Product IDNPC118423
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6-Oxo-7,11,13-Labdatriene-16,15-Olide
IUPAC Name 4-[(E)-2-[(1S,4aS,8aR)-2,5,5,8a-tetramethyl-4-oxo-4a,6,7,8-tetrahydro-1H-naphthalen-1-yl]ethenyl]-2H-furan-5-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1288184
PubChem CID 52942511
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 WFORKFWUKJWGDY-FKGFIRTRSA-N
Standard InCHI InChI=1S/C20H26O3/c1-13-12-16(21)17-19(2,3)9-5-10-20(17,4)15(13)7-6-14-8-11-23-18(14)22/h6-8,12,15,17H,5,9-11H2,1-4H3/b7-6+/t15-,17-,20+/m0/s1
SMILES CC1=CC(=O)[C@H]2C(C)(C)CCC[C@]2(C)[C@H]1/C=C/C1=CCOC1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.19 Volume:   341.995
?
Van der Waals volume.
Dense:   0.919 LogP:   3.448
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.384
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.196
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.723 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.482 Fsp3:   0.6
MCE-18:   52.5
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.574 Fluc inhibitor:   0.727
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.183
?
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:   0.751 Promiscuous compounds:   0.218

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.587 MDCK Permeability:   -4.539
Pgp-inhibitor:   0.916 Pgp-substrate:   0.011
PAMPA:   0.059
?
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):   0.036
20% Bioavailability (F20%):   0.084 30% Bioavailability (F30%):   0.126
50% Bioavailability (F50%):   0.666

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.114 MRP1:   0.465
Plasma Protein Binding (PPB):   98.184% Volume Distribution (VD):   -0.149
Fu: 1.923%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.959 BCRP inhibitor:   0.037
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.01 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.586
CYP2C9-inhibitor:   0.049 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.451
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.744
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.97
?
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):  6.549 Half-life (T1/2):  0.762

ADMET: Toxicity

hERG Blockers:  0.098 hERG Blockers (10um):  0.494
Human Hepatotoxicity (H-HT):  0.603 Drug-induced Liver Injury (DILI):  0.748
AMES Toxicity:  0.742 Rat Oral Acute Toxicity:  0.701
Maximum Recommended Daily Dose:  0.738 Skin Sensitization:  0.986
Carcinogencity:  0.883 Eye Corrosion:  0.01
Eye Irritation:  0.468 Respiratory Toxicity:  0.672
Drug-induced Neurotoxicity:  0.545 Ototoxicity:  0.266
Hematotoxicity:  0.648 Drug-induced Nephrotoxicity:  0.881
Genotoxicity:  0.975 RPMI-8226 Immunitoxicity:  0.286
A549 Cytotoxicity:  0.109 Hek293 Cytotoxicity:  0.455
BCF:   2.074
?
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:   4.771
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.653
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.113
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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
NPO25518 Hedychium coronarium Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[21106458]
NPO25518 Hedychium coronarium Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[37514241]
NPO25518 Hedychium coronarium Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39317685]
NPO25518 Hedychium coronarium Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25518 Hedychium coronarium Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25518 Hedychium coronarium Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25518 Hedychium coronarium Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25518 Hedychium coronarium Species Zingiberaceae 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
NPT81 Cell line A549 Homo sapiens GI50 = 21700.0 nM PMID[23806110]
NPT136 Cell line SK-N-SH Homo sapiens GI50 = 8200.0 nM Open TG-GATES in vivo data: Biochemistry
NPT83 Cell line MCF7 Homo sapiens GI50 = 15700.0 nM PMID[15921421]
NPT165 Cell line HeLa Homo sapiens GI50 = 83600.0 nM PMID[19581457]

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 NPC118423 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
0.8085 Intermediate Similarity NPC168248
0.7083 Intermediate Similarity NPC268122
0.6939 Remote Similarity NPC469939
0.5849 Remote Similarity NPC242069
0.5741 Remote Similarity NPC196407
0.566 Remote Similarity NPC4509
0.5357 Remote Similarity NPC473153
0.5357 Remote Similarity NPC182136
0.5094 Remote Similarity NPC476346

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC118423 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