Natural Product: NPC78746

Natural Product IDNPC78746
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Decursinol
IUPAC Name (3S)-3-hydroxy-2,2-dimethyl-3,4-dihydropyrano[3,2-g]chromen-8-one
Synonyms (+)-Decursinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL481657
PubChem CID 442127
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0003484] Pyranocoumarins
          • [CHEMONTID:0003486] Linear pyranocoumarins

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 BGXFQDFSVDZUIW-LBPRGKRZSA-N
Standard InCHI InChI=1S/C14H14O4/c1-14(2)12(15)6-9-5-8-3-4-13(16)17-10(8)7-11(9)18-14/h3-5,7,12,15H,6H2,1-2H3/t12-/m0/s1
SMILES CC1(C)[C@H](Cc2cc3ccc(=O)oc3cc2O1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.09 Volume:   247.009
?
Van der Waals volume.
Dense:   0.996 LogP:   1.66
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.74
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.595
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.721 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.126 Fsp3:   0.357
MCE-18:   59.684
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.437 Fluc inhibitor:   0.737
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.997
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.258
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.31 Promiscuous compounds:   0.187

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.687 MDCK Permeability:   -4.635
Pgp-inhibitor:   0.0 Pgp-substrate:   0.014
PAMPA:   0.886
?
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):   0.002
20% Bioavailability (F20%):   0.918 30% Bioavailability (F30%):   0.716
50% Bioavailability (F50%):   0.857

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.999
Plasma Protein Binding (PPB):   80.903% Volume Distribution (VD):   -0.009
Fu: 20.693%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.884
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.001
BSEP inhibitor:   0.901

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.014
CYP2C19-inhibitor:   0.29 CYP2C19-substrate:   0.028
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.071
CYP3A4-inhibitor:   0.822 CYP3A4-substrate:   0.903
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.925
HLM stability:   0.525
?
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):  8.081 Half-life (T1/2):  0.766

ADMET: Toxicity

hERG Blockers:  0.138 hERG Blockers (10um):  0.417
Human Hepatotoxicity (H-HT):  0.537 Drug-induced Liver Injury (DILI):  0.743
AMES Toxicity:  0.698 Rat Oral Acute Toxicity:  0.802
Maximum Recommended Daily Dose:  0.785 Skin Sensitization:  0.568
Carcinogencity:  0.83 Eye Corrosion:  0.058
Eye Irritation:  0.918 Respiratory Toxicity:  0.952
Drug-induced Neurotoxicity:  0.463 Ototoxicity:  0.377
Hematotoxicity:  0.288 Drug-induced Nephrotoxicity:  0.419
Genotoxicity:  0.845 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.383 Hek293 Cytotoxicity:  0.389
BCF:   0.39
?
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:   3.016
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.565
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.82
?
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
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[11374978]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[15679317]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[17997069]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11438 Angelica gigas Species Apiaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens IC50 = 28000.0 nM PMID[11374978]
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 5623.4 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT740 Individual protein Beta-secretase 1 Homo sapiens IC50 > 500000.0 nM PMID[22222157]
NPT740 Individual protein Beta-secretase 1 Homo sapiens Inhibition = 7.6 % PMID[22222157]
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 16353.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT169 Cell line B16-F10 Mus musculus Inhibition = 12.2 % PMID[20884093]
NPT2 Others Unspecified n.a. Activity = 33.4 % PMID[15679317]
NPT2 Others Unspecified n.a. Activity = 69.6 % PMID[15679317]
NPT2 Others Unspecified n.a. Activity = 40.7 % PMID[15679317]

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 NPC78746 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
0.6667 Remote Similarity NPC111347
0.6607 Remote Similarity NPC76753
0.625 Remote Similarity NPC253574
0.625 Remote Similarity NPC98179
0.5965 Remote Similarity NPC188380
0.5965 Remote Similarity NPC224543
0.5965 Remote Similarity NPC72281
0.5789 Remote Similarity NPC248429
0.569 Remote Similarity NPC234109
0.569 Remote Similarity NPC188327
0.5652 Remote Similarity NPC85624
0.5593 Remote Similarity NPC601133
0.5593 Remote Similarity NPC608534
0.5538 Remote Similarity NPC119640
0.5538 Remote Similarity NPC183646
0.5507 Remote Similarity NPC211110
0.55 Remote Similarity NPC204353
0.5455 Remote Similarity NPC605579
0.5429 Remote Similarity NPC279573
0.5424 Remote Similarity NPC257188
0.5385 Remote Similarity NPC30655
0.5385 Remote Similarity NPC45124
0.5373 Remote Similarity NPC207002
0.5373 Remote Similarity NPC133956
0.5373 Remote Similarity NPC47163
0.5278 Remote Similarity NPC296377
0.5167 Remote Similarity NPC36414

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC78746 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