Natural Product: NPC478126

Natural Product IDNPC478126
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2(3H)-Benzofuranone, hexahydro-4,4,7a-trimethyl-
IUPAC Name 4,4,7a-trimethyl-3a,5,6,7-tetrahydro-3H-1-benzofuran-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 536454
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000301] Benzofurans

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 IGSYVKHPYSDDQD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C11H18O2/c1-10(2)5-4-6-11(3)8(10)7-9(12)13-11/h8H,4-7H2,1-3H3
SMILES CC1(CCCC2(C1CC(=O)O2)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   182.13 Volume:   196.643
?
Van der Waals volume.
Dense:   0.926 LogP:   2.273
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.383
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.001
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   11.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.538 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.612 Fsp3:   0.909
MCE-18:   37.333
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.03 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.023
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.968 Promiscuous compounds:   0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.651 MDCK Permeability:   -4.714
Pgp-inhibitor:   0.658 Pgp-substrate:   0.005
PAMPA:   0.055
?
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):   0.001
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.005
50% Bioavailability (F50%):   0.07

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.669 MRP1:   0.942
Plasma Protein Binding (PPB):   95.042% Volume Distribution (VD):   0.304
Fu: 6.874%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.331
OATP1B3 inhibitor:   0.743 BCRP inhibitor:   0.009
BSEP inhibitor:   0.81

ADMET: Metabolism

CYP1A2-inhibitor:   0.02 CYP1A2-substrate:   0.487
CYP2C19-inhibitor:   0.876 CYP2C19-substrate:   0.088
CYP2C9-inhibitor:   0.782 CYP2C9-substrate:   0.099
CYP2D6-inhibitor:   0.51 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.061 CYP3A4-substrate:   0.011
CYP2B6-substrate:   0.88 CYP2C8-inhibitor:   0.755
HLM stability:   0.975
?
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):  8.754 Half-life (T1/2):  0.903

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.541
Human Hepatotoxicity (H-HT):  0.492 Drug-induced Liver Injury (DILI):  0.446
AMES Toxicity:  0.267 Rat Oral Acute Toxicity:  0.171
Maximum Recommended Daily Dose:  0.434 Skin Sensitization:  0.932
Carcinogencity:  0.61 Eye Corrosion:  0.98
Eye Irritation:  0.992 Respiratory Toxicity:  0.555
Drug-induced Neurotoxicity:  0.638 Ototoxicity:  0.393
Hematotoxicity:  0.332 Drug-induced Nephrotoxicity:  0.502
Genotoxicity:  0.01 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.057 Hek293 Cytotoxicity:  0.068
BCF:   1.04
?
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:   3.39
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.888
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.455
?
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
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[10993146]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. Tsukuba, Japan 1998-JUN PMID[12381108]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. leaf n.a. PMID[24197199]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[24254087]
NPO62123 Ajuga turkestanica Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[29468889]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. PMID[31861466]
NPO62123 Ajuga turkestanica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8589 Triticum aestivum Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8589 Triticum aestivum Species Poaceae 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
NPO62123 Ajuga turkestanica Oil n.a. 5.4 n.a. n.a. % PMID[29468889]

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
NPT119 Organism Triticum aestivum Triticum aestivum GI = 0 % PMID[12381108]
NPT119 Organism Triticum aestivum Triticum aestivum Inhibition = 0 % PMID[12381108]

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 NPC478126 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
0.6316 Remote Similarity NPC84562
0.6316 Remote Similarity NPC608369

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC478126 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