Natural Product: NPC204105

Natural Product IDNPC204105
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4,8-Bis-Epi-Inuviscolide
IUPAC Name (3aR,5aS,8S,8aR,9aR)-8-hydroxy-8-methyl-1,5-dimethylidene-3a,4,5a,6,7,8a,9,9a-octahydroazuleno[6,5-b]furan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1912052
PubChem CID 57398175
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:0001770] Guaianolides 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 GTYUWNQOOLJZBM-HVNMYJMUSA-N
Standard InCHI InChI=1S/C15H20O3/c1-8-6-13-11(9(2)14(16)18-13)7-12-10(8)4-5-15(12,3)17/h10-13,17H,1-2,4-7H2,3H3/t10-,11-,12-,13-,15+/m1/s1
SMILES C=C1C[C@@H]2[C@H](C[C@@H]3[C@@H]1CC[C@]3(C)O)C(=C)C(=O)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   248.14 Volume:   260.788
?
Van der Waals volume.
Dense:   0.952 LogP:   1.626
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.593
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.367
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.406 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.588 Fsp3:   0.667
MCE-18:   51.68
?
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:   0.28 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
?
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:   0.792 Promiscuous compounds:   0.623

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.757 MDCK Permeability:   -4.817
Pgp-inhibitor:   0.336 Pgp-substrate:   0.058
PAMPA:   0.066
?
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):   0.019
20% Bioavailability (F20%):   0.642 30% Bioavailability (F30%):   0.914
50% Bioavailability (F50%):   0.912

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.889
Plasma Protein Binding (PPB):   56.117% Volume Distribution (VD):   0.008
Fu: 45.115%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.257
BSEP inhibitor:   0.933

ADMET: Metabolism

CYP1A2-inhibitor:   0.891 CYP1A2-substrate:   0.035
CYP2C19-inhibitor:   0.89 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.492 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.032
CYP3A4-inhibitor:   0.005 CYP3A4-substrate:   0.447
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.737
HLM stability:   0.373
?
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):  7.04 Half-life (T1/2):  1.886

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.227
Human Hepatotoxicity (H-HT):  0.82 Drug-induced Liver Injury (DILI):  0.454
AMES Toxicity:  0.631 Rat Oral Acute Toxicity:  0.513
Maximum Recommended Daily Dose:  0.708 Skin Sensitization:  0.97
Carcinogencity:  0.869 Eye Corrosion:  0.086
Eye Irritation:  0.934 Respiratory Toxicity:  0.458
Drug-induced Neurotoxicity:  0.688 Ototoxicity:  0.543
Hematotoxicity:  0.391 Drug-induced Nephrotoxicity:  0.746
Genotoxicity:  0.677 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.51 Hek293 Cytotoxicity:  0.498
BCF:   0.452
?
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:   3.121
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.67
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.881
?
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
NPO22238 Inula falconeri Species Asteraceae Eukaryota aerial parts Tibet, China n.a. PMID[21924800]
NPO22238 Inula falconeri Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22238 Inula falconeri 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 7300.0 nM PMID[26034885]

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 NPC204105 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 NPC284534
1.0 High Similarity NPC300082
1.0 High Similarity NPC40729
0.6809 Remote Similarity NPC216284
0.6327 Remote Similarity NPC258965
0.6327 Remote Similarity NPC156658
0.62 Remote Similarity NPC301969
0.62 Remote Similarity NPC480216
0.62 Remote Similarity NPC37607
0.6038 Remote Similarity NPC488305
0.6 Remote Similarity NPC215556
0.551 Remote Similarity NPC603081
0.5385 Remote Similarity NPC67493
0.52 Remote Similarity NPC79549
0.5192 Remote Similarity NPC245665

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC204105 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