Natural Product: NPC304954

Natural Product IDNPC304954
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sid26657808
IUPAC Name (2Z)-6-hydroxy-2-[(4-hydroxy-3-methoxyphenyl)methylidene]-1-benzofuran-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL446827
PubChem CID 16376440
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0001631] Aurone flavonoids

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 HPSPCMSCDNHZJM-CHHVJCJISA-N
Standard InCHI InChI=1S/C16H12O5/c1-20-14-6-9(2-5-12(14)18)7-15-16(19)11-4-3-10(17)8-13(11)21-15/h2-8,17-18H,1H3/b15-7-
SMILES COc1cc(ccc1O)/C=C/1Oc2c(C1=O)ccc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.07 Volume:   282.482
?
Van der Waals volume.
Dense:   1.006 LogP:   2.531
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.704
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.319
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.829 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.25 Fsp3:   0.062
MCE-18:   34.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.643 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.786
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.715
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.538 Promiscuous compounds:   0.501

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.241 MDCK Permeability:   -4.915
Pgp-inhibitor:   0.528 Pgp-substrate:   0.002
PAMPA:   0.192
?
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):   0.05
20% Bioavailability (F20%):   0.575 30% Bioavailability (F30%):   0.699
50% Bioavailability (F50%):   0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.265
Plasma Protein Binding (PPB):   96.803% Volume Distribution (VD):   -0.559
Fu: 2.395%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.066
BSEP inhibitor:   0.931

ADMET: Metabolism

CYP1A2-inhibitor:   0.883 CYP1A2-substrate:   0.992
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.803
CYP2C9-inhibitor:   0.027 CYP2C9-substrate:   0.012
CYP2D6-inhibitor:   0.261 CYP2D6-substrate:   0.989
CYP3A4-inhibitor:   0.024 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.539
?
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):  5.553 Half-life (T1/2):  1.388

ADMET: Toxicity

hERG Blockers:  0.067 hERG Blockers (10um):  0.489
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.538
AMES Toxicity:  0.619 Rat Oral Acute Toxicity:  0.446
Maximum Recommended Daily Dose:  0.651 Skin Sensitization:  0.986
Carcinogencity:  0.785 Eye Corrosion:  0.209
Eye Irritation:  0.991 Respiratory Toxicity:  0.325
Drug-induced Neurotoxicity:  0.319 Ototoxicity:  0.211
Hematotoxicity:  0.229 Drug-induced Nephrotoxicity:  0.297
Genotoxicity:  0.726 RPMI-8226 Immunitoxicity:  0.127
A549 Cytotoxicity:  0.422 Hek293 Cytotoxicity:  0.774
BCF:   1.115
?
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:   3.699
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.52
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.032
?
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
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota seeds n.a. n.a. PMID[12762787]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12762809]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5140 Dipteryx odorata Species Fabaceae 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
NPT1038 Individual protein Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 70794.6 nM PMID[21265542]
NPT1005 Individual protein Tumor susceptibility gene 101 protein Homo sapiens Potency n.a. 50118.7 nM PMID[17958396]
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 100000.0 nM PMID[19782567]
NPT2971 Individual protein DNA dC->dU-editing enzyme APOBEC-3F Homo sapiens Potency n.a. 35481.3 nM PMID[24013413]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 25929.0 nM PubChem BioAssay data set
NPT1852 Individual protein Rac GTPase-activating protein 1 Homo sapiens IC50 n.a. 26050.0 nM PMID[16252907]
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 2818.4 nM PMID[22487595]
NPT157 Individual protein Breast cancer type 1 susceptibility protein Homo sapiens Potency n.a. 12589.3 nM PMID[18303847]
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 28183.8 nM PMID[18243700]
NPT1417 Individual protein Transcriptional regulator ERG Homo sapiens Potency n.a. 50118.7 nM PMID[19734910]
NPT105 Individual protein Muscleblind-like protein 1 Homo sapiens Potency n.a. 11220.2 nM PMID[17958396]
NPT2797 Individual protein Pancreatic lipase Homo sapiens Inhibition = 77.7 % PMID[38052378]
NPT537 Individual protein Ras-related protein Rab-9A Homo sapiens Potency = 3981.1 nM PMID[17253864]
NPT803 Individual protein Flap endonuclease 1 Homo sapiens Potency n.a. 15848.9 nM PMID[19459643]
NPT28417 Single protein Beta-lactamase NDM-1 Bacteria Inhibition <= 10.0 % PMID[38109811]
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 25118.9 nM PMID[22136907]
NPT538 Individual protein Niemann-Pick C1 protein Homo sapiens Potency = 3162.3 nM DOI[10.6019/CHEMBL1201861]
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 8492.1 nM PMID[17353252]
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 2511.9 nM PMID[12088423]
NPT60 Individual protein Lysosomal alpha-glucosidase Homo sapiens Potency = 50118.7 nM PMID[17350734]
NPT59 Individual protein DNA polymerase beta Homo sapiens Potency = 79432.8 nM PMID[26241103]
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 1995.3 nM PMID[20621475]
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 18887.6 nM PMID[12350153]
NPT821 Individual protein Werner syndrome ATP-dependent helicase Homo sapiens Potency n.a. 56234.1 nM PMID[22100140]
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 15848.9 nM PMID[11141096]
NPT440 Individual protein Quinone oxidoreductase Mus musculus CD = 6.4 uM PMID[23350733]
NPT45 Individual protein Ubiquitin carboxyl-terminal hydrolase 2 Homo sapiens Potency = 11220.2 nM PMID[16989518]
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 19952.6 nM PMID[15026054]
NPT47 Individual protein ATP-dependent DNA helicase Q1 Homo sapiens Potency = 28183.8 nM PMID[18077425]
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 5211.9 nM PMID[25856683]
NPT442 Individual protein Ferritin light chain Equus caballus Potency = 31622.8 nM DrugMatrix in vivo data: Pathology
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 39810.7 nM PMID[10924166]
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency n.a. 7079.5 nM PMID[8277308]
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 23099.9 nM DOI[10.6019/CHEMBL1201861]
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 16353.5 nM PMID[26034885]
NPT47 Individual protein ATP-dependent DNA helicase Q1 Homo sapiens Potency n.a. 79432.8 nM PMID[17194835]
NPT84 Individual protein Dual specificity tyrosine-phosphorylation-regulated kinase 1A Rattus norvegicus AC50 = 641.0 nM PMID[10924160]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 794.3 nM PMID[18183025]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 18.5 nM PMID[19581457]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 5221.3 nM Open TG-GATES in vivo data: Organ Weight
NPT28438 Unchecked Unchecked n.a. Inhibition = 13.0 % PMID[38109811]
NPT28438 Unchecked Unchecked n.a. Inhibition = 14.0 % PMID[38109811]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 34600.0 nM PMID[12762787]
NPT2 Others Unspecified n.a. Ratio = 5.4 n.a. PMID[23009169]
NPT2 Others Unspecified n.a. Inhibition = 48.2 % PMID[22694318]
NPT2 Others Unspecified n.a. Potency = 16360.1 nM PMID[20855742]
NPT2 Others Unspecified n.a. Potency n.a. 6309.6 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 3548.1 nM PMID[22224661]
NPT2 Others Unspecified n.a. IC50 n.a. 33860.0 nM PMID[25084548]
NPT2 Others Unspecified n.a. Potency n.a. 12589.3 nM PMID[17958396]
NPT2 Others Unspecified n.a. Potency n.a. 10000.0 nM PMID[1847431]
NPT2 Others Unspecified n.a. Potency n.a. 5623.4 nM PMID[17844994]

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 NPC304954 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
0.7447 Intermediate Similarity NPC254841
0.6863 Remote Similarity NPC140840
0.6863 Remote Similarity NPC86847
0.5345 Remote Similarity NPC233724

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC304954 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