Natural Product: NPC217602

Natural Product IDNPC217602
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-5-Hydroxy-2-(1-Hydroxyethyl)Naphtho[2,3-B]Furan-4,9-Dione
IUPAC Name 5-hydroxy-2-[(1S)-1-hydroxyethyl]benzo[f][1]benzofuran-4,9-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL392591
PubChem CID 14159819
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001634] Naphthofurans

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 XJGFVZBTNKODFQ-LURJTMIESA-N
Standard InCHI InChI=1S/C14H10O5/c1-6(15)10-5-8-12(17)11-7(3-2-4-9(11)16)13(18)14(8)19-10/h2-6,15-16H,1H3/t6-/m0/s1
SMILES C[C@@H](c1cc2C(=O)c3c(cccc3O)C(=O)c2o1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.05 Volume:   250.527
?
Van der Waals volume.
Dense:   1.03 LogP:   2.147
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.348
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.029
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   87.74
?
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:   0.695 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.124 Fsp3:   0.143
MCE-18:   54.0
?
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:   0 PAINS Alert:   1
Colloidal aggregators:   0.159 Fluc inhibitor:   0.571
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.474
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.445
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.342 Promiscuous compounds:   0.367

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.737 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.638 Pgp-substrate:   0.032
PAMPA:   0.659
?
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):   0.409
20% Bioavailability (F20%):   0.179 30% Bioavailability (F30%):   0.939
50% Bioavailability (F50%):   0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.404
Plasma Protein Binding (PPB):   82.041% Volume Distribution (VD):   0.519
Fu: 18.584%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.424
BSEP inhibitor:   0.659

ADMET: Metabolism

CYP1A2-inhibitor:   0.062 CYP1A2-substrate:   0.98
CYP2C19-inhibitor:   0.057 CYP2C19-substrate:   0.121
CYP2C9-inhibitor:   0.09 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.033 CYP2D6-substrate:   0.017
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.835
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.644
?
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):  3.922 Half-life (T1/2):  1.309

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.26
Human Hepatotoxicity (H-HT):  0.886 Drug-induced Liver Injury (DILI):  0.983
AMES Toxicity:  0.892 Rat Oral Acute Toxicity:  0.73
Maximum Recommended Daily Dose:  0.852 Skin Sensitization:  0.84
Carcinogencity:  0.915 Eye Corrosion:  0.001
Eye Irritation:  0.884 Respiratory Toxicity:  0.889
Drug-induced Neurotoxicity:  0.384 Ototoxicity:  0.272
Hematotoxicity:  0.638 Drug-induced Nephrotoxicity:  0.498
Genotoxicity:  0.996 RPMI-8226 Immunitoxicity:  0.281
A549 Cytotoxicity:  0.661 Hek293 Cytotoxicity:  0.527
BCF:   1.634
?
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:   3.828
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.983
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.347
?
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
NPO30968 Tabebuia impetiginosa Species Bignoniaceae Eukaryota n.a. n.a. n.a. DOI[10.1039/P19910002323]
NPO31330 Tabebuia ochracea Species Bignoniaceae Eukaryota n.a. stem n.a. DOI[10.1076/phbi.35.4.227.13306]
NPO30050 Tabebuia incana Species Bignoniaceae Eukaryota n.a. bark n.a. DOI[10.1590/S0044-59672007000100011]
NPO487 Tabebuia avellanedae Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[17950604]
NPO487 Tabebuia avellanedae Species Bignoniaceae Eukaryota n.a. bark n.a. PMID[17950604]
NPO487 Tabebuia avellanedae Species Bignoniaceae Eukaryota n.a. Brazilian n.a. PMID[19674905]
NPO487 Tabebuia avellanedae Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[32044231]
NPO30968 Tabebuia impetiginosa Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3751 Orthantha lutea n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO487 Tabebuia avellanedae Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12083 Hydnellum zonatum Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO487 Tabebuia avellanedae Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3751 Orthantha lutea n.a. n.a. n.a. 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
NPT1689 Individual protein Tyrosine-protein kinase JAK1 Homo sapiens Inhibition = 94.8 % PMID[32044231]
NPT3246 Individual protein Tyrosine-protein kinase JAK2 Homo sapiens Inhibition = 80.6 % PMID[32044231]
NPT38 Individual protein Signal transducer and activator of transcription 3 Homo sapiens Inhibition = 100.0 % PMID[32044231]
NPT38 Individual protein Signal transducer and activator of transcription 3 Homo sapiens IC50 = 2000.0 nM PMID[32044231]
NPT38 Individual protein Signal transducer and activator of transcription 3 Homo sapiens Activity = 76.0 % PMID[32044231]
NPT38 Individual protein Signal transducer and activator of transcription 3 Homo sapiens Activity = 75.0 % PMID[32044231]
NPT38 Individual protein Signal transducer and activator of transcription 3 Homo sapiens Activity = 43.0 % PMID[32044231]
NPT38 Individual protein Signal transducer and activator of transcription 3 Homo sapiens Activity = 3.0 % PMID[32044231]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT306 Cell line PC-3 Homo sapiens EC50 = 140.0 nM PMID[19674905]
NPT81 Cell line A549 Homo sapiens EC50 = 960.0 nM PMID[17950604]
NPT83 Cell line MCF7 Homo sapiens EC50 = 3500.0 nM PMID[17950604]
NPT80 Cell line Raji Homo sapiens Activity = 60.0 % PMID[19674905]
NPT80 Cell line Raji Homo sapiens Activity > 80.0 % PMID[17950604]
NPT83 Cell line MCF7 Homo sapiens EC50 = 510.0 nM PMID[19674905]
NPT81 Cell line A549 Homo sapiens EC50 = 780.0 nM PMID[19674905]
NPT611 Cell line Hepatocyte Homo sapiens EC50 = 11100.0 nM PMID[19674905]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 410.0 nM PMID[32044231]
NPT83 Cell line MCF7 Homo sapiens IC50 = 500.0 nM PMID[32044231]
NPT81 Cell line A549 Homo sapiens IC50 = 130.0 nM PMID[32044231]
NPT81 Cell line A549 Homo sapiens IC50 = 160.0 nM PMID[37343498]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 350.0 nM PMID[37343498]
NPT3658 Organism Bacillus mycoides Bacillus mycoides MIC = 0.78 ug.mL-1 PMID[19674905]
NPT3656 Organism Paecilomyces variotii Paecilomyces variotii MIC = 25.0 ug.mL-1 PMID[19674905]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 0.78 ug.mL-1 PMID[19674905]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 3.13 ug.mL-1 PMID[19674905]
NPT20 Organism Candida albicans Candida albicans MIC = 25.0 ug.mL-1 PMID[19674905]
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 Inhibition = 0.0 % PMID[17950604]
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 Inhibition = 4.4 % PMID[17950604]
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 Inhibition = 16.9 % PMID[17950604]
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 Inhibition = 50.0 % PMID[17950604]
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 IC50 = 33200.0 nM PMID[17950604]
NPT3657 Organism Cryptococcus albidus Cryptococcus albidus MIC = 1.56 ug.mL-1 PMID[19674905]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 3.13 ug.mL-1 PMID[19674905]
NPT87 Organism Aspergillus fumigatus Aspergillus fumigatus MIC = 12.5 ug.mL-1 PMID[19674905]
NPT3086 Organism Penicillium expansum Penicillium expansum MIC = 25.0 ug.mL-1 PMID[19674905]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[19674905]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 100.0 ug.mL-1 PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 67.0 % PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 7.0 % PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 47.0 % PMID[19674905]
NPT3608 Organism Salmonella enteritidis Salmonella enterica subsp. enterica serovar Enteritidis MIC > 100.0 ug.mL-1 PMID[19674905]
NPT2 Others Unspecified n.a. IC50 = 33200.0 nM PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 50.0 % PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 16.9 % PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 4.4 % PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 0.0 % PMID[19674905]
NPT2 Others Unspecified n.a. Activity = 3.9 n.a. PMID[19674905]

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 NPC217602 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 NPC473282
1.0 High Similarity NPC104380
0.8222 Intermediate Similarity NPC476404
0.8222 Intermediate Similarity NPC294300
0.8222 Intermediate Similarity NPC317900
0.7391 Intermediate Similarity NPC226578
0.6889 Remote Similarity NPC471613
0.6889 Remote Similarity NPC289955
0.6 Remote Similarity NPC252208

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC217602 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