Natural Product: NPC470239

Natural Product IDNPC470239
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 10-Epi-4H-Tomentosin
IUPAC Name (3aR,7R,8aS)-6-(3-hydroxybutyl)-7-methyl-3-methylidene-4,7,8,8a-tetrahydro-3aH-cyclohepta[b]furan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1912041
PubChem CID 57399823
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:0000502] Xanthanolides

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 KQEADOUDJYBGFC-HBUSVSKJSA-N
Standard InCHI InChI=1S/C15H22O3/c1-9-8-14-13(11(3)15(17)18-14)7-6-12(9)5-4-10(2)16/h6,9-10,13-14,16H,3-5,7-8H2,1-2H3/t9-,10?,13-,14+/m1/s1
SMILES CC(CCC1=CC[C@H]2[C@H](C[C@H]1C)OC(=O)C2=C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   250.16 Volume:   269.345
?
Van der Waals volume.
Dense:   0.929 LogP:   3.031
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.87
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.509
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   13.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.476 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.312 Fsp3:   0.667
MCE-18:   31.2
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.282 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.012
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.869 Promiscuous compounds:   0.107

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.903 MDCK Permeability:   -4.703
Pgp-inhibitor:   0.171 Pgp-substrate:   0.157
PAMPA:   0.528
?
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):   0.048
20% Bioavailability (F20%):   0.125 30% Bioavailability (F30%):   0.805
50% Bioavailability (F50%):   0.949

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.109 MRP1:   0.682
Plasma Protein Binding (PPB):   60.119% Volume Distribution (VD):   0.072
Fu: 40.311%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.159
BSEP inhibitor:   0.882

ADMET: Metabolism

CYP1A2-inhibitor:   0.216 CYP1A2-substrate:   0.005
CYP2C19-inhibitor:   0.058 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.228 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.023
CYP3A4-inhibitor:   0.37 CYP3A4-substrate:   0.029
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.188
HLM stability:   0.199
?
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):  7.129 Half-life (T1/2):  1.469

ADMET: Toxicity

hERG Blockers:  0.046 hERG Blockers (10um):  0.239
Human Hepatotoxicity (H-HT):  0.596 Drug-induced Liver Injury (DILI):  0.654
AMES Toxicity:  0.351 Rat Oral Acute Toxicity:  0.084
Maximum Recommended Daily Dose:  0.549 Skin Sensitization:  0.896
Carcinogencity:  0.614 Eye Corrosion:  0.638
Eye Irritation:  0.962 Respiratory Toxicity:  0.33
Drug-induced Neurotoxicity:  0.237 Ototoxicity:  0.656
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.616
Genotoxicity:  0.032 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.42 Hek293 Cytotoxicity:  0.193
BCF:   0.541
?
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:   3.245
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.87
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.096
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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
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 = 870.0 nM PubChem BioAssay data set

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 NPC470239 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 NPC470244
1.0 High Similarity NPC486582
0.7273 Intermediate Similarity NPC193351
0.7273 Intermediate Similarity NPC226669
0.7273 Intermediate Similarity NPC138408
0.6957 Remote Similarity NPC470240
0.6809 Remote Similarity NPC483167
0.6531 Remote Similarity NPC476794
0.6522 Remote Similarity NPC472966
0.6522 Remote Similarity NPC486581
0.6 Remote Similarity NPC472960
0.5745 Remote Similarity NPC63649
0.5745 Remote Similarity NPC264227
0.5294 Remote Similarity NPC318468
0.5185 Remote Similarity NPC116177

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470239 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