Natural Product: NPC59459

Natural Product IDNPC59459
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VMUMUNGCHYCMDR-SSDOTTSWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2386326
PubChem CID 73353443
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000023] Naphthalenes
        • [CHEMONTID:0000153] Naphthoquinones

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 VMUMUNGCHYCMDR-SSDOTTSWSA-N
Standard InCHI InChI=1S/C15H14O4/c1-6-4-9(16)10-7(2)5-19-15-8(3)13(17)14(18)11(6)12(10)15/h4,7,16H,5H2,1-3H3/t7-/m1/s1
SMILES O=C1C(=C2OC[C@H](c3c2c(C1=O)c(C)cc3O)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.09 Volume:   261.669
?
Van der Waals volume.
Dense:   0.986 LogP:   1.858
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.139
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.369
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   63.6
?
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:   0.725 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.651 Fsp3:   0.333
MCE-18:   60.8
?
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:   0.449 Fluc inhibitor:   0.477
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.458
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.406
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.441 Promiscuous compounds:   0.202

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.667 MDCK Permeability:   -4.646
Pgp-inhibitor:   0.714 Pgp-substrate:   0.068
PAMPA:   0.595
?
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):   0.078
20% Bioavailability (F20%):   0.66 30% Bioavailability (F30%):   0.956
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.973
Plasma Protein Binding (PPB):   97.48% Volume Distribution (VD):   0.043
Fu: 2.395%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.008
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.025 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.041 CYP2C9-substrate:   0.091
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.837
CYP3A4-inhibitor:   0.836 CYP3A4-substrate:   0.971
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.808
?
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):  6.838 Half-life (T1/2):  1.013

ADMET: Toxicity

hERG Blockers:  0.025 hERG Blockers (10um):  0.321
Human Hepatotoxicity (H-HT):  0.918 Drug-induced Liver Injury (DILI):  0.979
AMES Toxicity:  0.945 Rat Oral Acute Toxicity:  0.594
Maximum Recommended Daily Dose:  0.733 Skin Sensitization:  0.998
Carcinogencity:  0.959 Eye Corrosion:  0.201
Eye Irritation:  0.973 Respiratory Toxicity:  0.692
Drug-induced Neurotoxicity:  0.721 Ototoxicity:  0.409
Hematotoxicity:  0.836 Drug-induced Nephrotoxicity:  0.947
Genotoxicity:  0.959 RPMI-8226 Immunitoxicity:  0.242
A549 Cytotoxicity:  0.343 Hek293 Cytotoxicity:  0.66
BCF:   1.7
?
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:   4.964
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.157
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.727
?
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
NPO6427 Wardomyces anomalus Species Microascaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np020518b]
NPO6427 Wardomyces anomalus Species Microascaceae Eukaryota n.a. n.a. n.a. PMID[12762814]
NPO19460 Karenia brevis Species Kareniaceae Eukaryota n.a. n.a. n.a. PMID[15679307]
NPO5167 Peripentadenia mearsii Species Elaeocarpaceae Eukaryota n.a. Australian rainforest n.a. PMID[18039010]
NPO19460 Karenia brevis Species Kareniaceae Eukaryota n.a. n.a. n.a. PMID[20218657]
NPO15986 Alangium chinense Species Cornaceae Eukaryota Roots n.a. n.a. PMID[23734721]
NPO25866 Kaunia lasiophthalma Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19460 Karenia brevis Species Kareniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO960 Phlomis aurea Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9565 Linum maritimum Species Linaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7535 Mansonia altissima Species Culicidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11354 Streptomyces galbus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO5167 Peripentadenia mearsii Species Elaeocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15986 Alangium chinense Species Cornaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13058 Psychotria brachyceras Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6427 Wardomyces anomalus Species Microascaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2124 Bulgaria inquinans Species Bulgariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17202 Lasallia asiae-orientalis Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10455 Vaccinium uliginosum Species Ericaceae Eukaryota n.a. n.a. Database[FooDB]
NPO15986 Alangium chinense Species Cornaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10455 Vaccinium uliginosum Species Ericaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO960 Phlomis aurea Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15986 Alangium chinense Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9794 Dysoxylum fraseranum Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10273 Dictyota flabellata Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11158 Diplopterygium rufopilosum Species Gleicheniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6427 Wardomyces anomalus Species Microascaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24924 Saara hardwickii Species Agamidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5167 Peripentadenia mearsii Species Elaeocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10455 Vaccinium uliginosum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO960 Phlomis aurea Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17202 Lasallia asiae-orientalis Species Umbilicariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3546 Shorea balangeran Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25866 Kaunia lasiophthalma Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8878 Polygala arenaria Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13058 Psychotria brachyceras Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15986 Alangium chinense Species Cornaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19460 Karenia brevis Species Kareniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7535 Mansonia altissima Species Culicidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6878 Vesperus xatarti Species Cerambycidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11510 Astragalus flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12123 Geodia gigas Species Geodiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4348 Watasenia scintillans Species Enoploteuthidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9565 Linum maritimum Species Linaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2124 Bulgaria inquinans Species Bulgariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6423 Vitex cauliflora Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11354 Streptomyces galbus Species Streptomycetaceae Bacteria 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
NPT1084 Subcellular Liver microsomes Rattus norvegicus IC50 = 17800.0 nM PMID[23734721]
NPT3494 Organism Coxsackievirus Coxsackievirus IC50 = 3100.0 nM PMID[23734721]

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
- Artemia salina LC50 = 50.7 ug.mL-1 PMID[25599949]

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 NPC59459 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
0.6154 Remote Similarity NPC135730
0.5741 Remote Similarity NPC263817

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59459 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