Natural Product: NPC137669

Natural Product IDNPC137669
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Prenyletin 6-Methyl Ether
IUPAC Name 6-methoxy-7-(3-methylbut-2-enoxy)chromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL594886
PubChem CID 1764914
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 ZLPLFUBVEZVYDX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H16O4/c1-10(2)6-7-18-14-9-12-11(8-13(14)17-3)4-5-15(16)19-12/h4-6,8-9H,7H2,1-3H3
SMILES COc1cc2ccc(=O)oc2cc1OCC=C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.1 Volume:   270.225
?
Van der Waals volume.
Dense:   0.963 LogP:   3.228
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.05
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.894
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.626 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.282 Fsp3:   0.267
MCE-18:   12.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.247 Fluc inhibitor:   0.527
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.989
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.502
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.588 Promiscuous compounds:   0.051

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.6 MDCK Permeability:   -4.561
Pgp-inhibitor:   0.012 Pgp-substrate:   0.001
PAMPA:   0.113
?
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):   0.004
20% Bioavailability (F20%):   0.946 30% Bioavailability (F30%):   0.995
50% Bioavailability (F50%):   0.871

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.948
Plasma Protein Binding (PPB):   89.808% Volume Distribution (VD):   -0.1
Fu: 10.727%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.22
BSEP inhibitor:   0.707

ADMET: Metabolism

CYP1A2-inhibitor:   0.021 CYP1A2-substrate:   0.598
CYP2C19-inhibitor:   0.807 CYP2C19-substrate:   0.039
CYP2C9-inhibitor:   0.886 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.887 CYP2D6-substrate:   0.484
CYP3A4-inhibitor:   0.975 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.842 CYP2C8-inhibitor:   0.996
HLM stability:   0.544
?
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):  7.327 Half-life (T1/2):  1.068

ADMET: Toxicity

hERG Blockers:  0.173 hERG Blockers (10um):  0.499
Human Hepatotoxicity (H-HT):  0.514 Drug-induced Liver Injury (DILI):  0.679
AMES Toxicity:  0.494 Rat Oral Acute Toxicity:  0.448
Maximum Recommended Daily Dose:  0.519 Skin Sensitization:  0.57
Carcinogencity:  0.729 Eye Corrosion:  0.222
Eye Irritation:  0.939 Respiratory Toxicity:  0.713
Drug-induced Neurotoxicity:  0.342 Ototoxicity:  0.176
Hematotoxicity:  0.343 Drug-induced Nephrotoxicity:  0.228
Genotoxicity:  0.744 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.054 Hek293 Cytotoxicity:  0.195
BCF:   1.174
?
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:   3.726
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.839
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.446
?
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
NPO10763 Aralia dasyphylla Species Araliaceae Eukaryota root bark n.a. n.a. PMID[10425135]
NPO13854 Prunus serotina Species Rosaceae Eukaryota n.a. kernel n.a. PMID[16652960]
NPO10051 Phyla nodiflora Species Verbenaceae Eukaryota n.a. aerial part n.a. PMID[25140335]
NPO20798 Echinodorus grandiflorus Species Alismataceae Eukaryota n.a. leaf n.a. PMID[26692456]
NPO8366 Gersemia fruticosa Species Nephtheidae Eukaryota n.a. n.a. n.a. PMID[26894524]
NPO18959 Neolitsea buisanensis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[37531297]
NPO13854 Prunus serotina Species Rosaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO17426 Vismia baccifera Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4687 Gyromitra esculenta Species Discinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19215 Ormosia semicastrata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14974.1 Nostoc commune var. flagelliforme Varieties Nostocaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12674 Colchicum ritchii Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8366 Gersemia fruticosa Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15830 Arachniodes maximowiczii Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21606 Monocyclanthus vignei Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20118 Hormothamnion enteromorphoides n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO19647 Palicourea crocea Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20885 Duguetia furfuracea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10051 Phyla nodiflora Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13854 Prunus serotina Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14974.1 Nostoc commune var. flagelliforme Varieties Nostocaceae Bacteria n.a. n.a. n.a. Database[MetaboLights]
NPO13854 Prunus serotina Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14974.1 Nostoc commune var. flagelliforme Varieties Nostocaceae Bacteria n.a. n.a. n.a. Database[TCMID]
NPO10051 Phyla nodiflora Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13854 Prunus serotina Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13704 Endarachne binghamiae Species Scytosiphonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18367 Cassia grandis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20725 Eysenhardtia adenostylis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13704 Endarachne binghamiae Species Scytosiphonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17731 Endiandra baillonii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8366 Gersemia fruticosa Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21606 Monocyclanthus vignei Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13854 Prunus serotina Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10763 Aralia dasyphylla Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17426 Vismia baccifera Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10051 Phyla nodiflora Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19215 Ormosia semicastrata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20798 Echinodorus grandiflorus Species Alismataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20919 Utetheisa ornatrix Species Erebidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4687 Gyromitra esculenta Species Discinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18959 Neolitsea buisanensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21835 Buxus rugulosa Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20118 Hormothamnion enteromorphoides n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO15750 Thymus nummularius Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15830 Arachniodes maximowiczii Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19458 Petunia axillaris Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20885 Duguetia furfuracea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19133 Brickellia baccharidea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14974.1 Nostoc commune var. flagelliforme Varieties Nostocaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO9531 Premna latifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12674 Colchicum ritchii Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19647 Palicourea crocea Species Rubiaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT466 Cell line U-937 Homo sapiens IC50 > 400000.0 nM PMID[19716307]
NPT466 Cell line U-937 Homo sapiens CC50 = 799000.0 nM PMID[19716307]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis FR50 = 0.43 n.a. DOI[10.1016/S0305-1978(96)00100-7]

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 = 17.6 ppm DOI[10.1016/S0305-1978(96)00100-7]

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 NPC137669 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
0.7963 Intermediate Similarity NPC241341
0.7119 Intermediate Similarity NPC164148
0.7119 Intermediate Similarity NPC43500
0.7111 Intermediate Similarity NPC240722
0.6538 Remote Similarity NPC281356
0.6296 Remote Similarity NPC309953
0.614 Remote Similarity NPC606257
0.6071 Remote Similarity NPC13067
0.5893 Remote Similarity NPC163200
0.58 Remote Similarity NPC7163
0.5763 Remote Similarity NPC20796
0.5323 Remote Similarity NPC180006
0.5312 Remote Similarity NPC233018
0.5238 Remote Similarity NPC19242
0.5172 Remote Similarity NPC248429
0.5156 Remote Similarity NPC235190
0.5098 Remote Similarity NPC87563
0.5098 Remote Similarity NPC265547
0.5077 Remote Similarity NPC224774

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC137669 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