Natural Product: NPC228184

Natural Product IDNPC228184
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Methoxy-2-Phenyl-2,3-Dihydrochromen-4-One
IUPAC Name 5-methoxy-2-phenyl-2,3-dihydrochromen-4-one
Synonyms 5-Methoxyflavanone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL317869
PubChem CID 147795
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002590] 5-O-methylated 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 YLLFUILNISGLHO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O3/c1-18-13-8-5-9-14-16(13)12(17)10-15(19-14)11-6-3-2-4-7-11/h2-9,15H,10H2,1H3
SMILES COc1cccc2c1C(=O)CC(O2)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   254.09 Volume:   267.538
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Van der Waals volume.
Dense:   0.95 LogP:   3.064
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.201
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.787
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   35.53
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.824 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.439 Fsp3:   0.188
MCE-18:   48.158
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.382 Fluc inhibitor:   0.569
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.272
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.407
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.634 Promiscuous compounds:   0.026

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.615 MDCK Permeability:   -4.671
Pgp-inhibitor:   0.994 Pgp-substrate:   0.005
PAMPA:   0.078
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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):   0.042
20% Bioavailability (F20%):   0.041 30% Bioavailability (F30%):   0.748
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.533 MRP1:   0.872
Plasma Protein Binding (PPB):   97.871% Volume Distribution (VD):   -0.0
Fu: 1.26%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.78
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.609
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.167 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.235 CYP2C19-substrate:   0.987
CYP2C9-inhibitor:   0.121 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.957
CYP3A4-inhibitor:   0.023 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.666
HLM stability:   0.638
?
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):  4.289 Half-life (T1/2):  0.926

ADMET: Toxicity

hERG Blockers:  0.304 hERG Blockers (10um):  0.616
Human Hepatotoxicity (H-HT):  0.8 Drug-induced Liver Injury (DILI):  0.64
AMES Toxicity:  0.657 Rat Oral Acute Toxicity:  0.54
Maximum Recommended Daily Dose:  0.468 Skin Sensitization:  0.513
Carcinogencity:  0.746 Eye Corrosion:  0.024
Eye Irritation:  0.943 Respiratory Toxicity:  0.447
Drug-induced Neurotoxicity:  0.775 Ototoxicity:  0.37
Hematotoxicity:  0.513 Drug-induced Nephrotoxicity:  0.725
Genotoxicity:  0.254 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.153 Hek293 Cytotoxicity:  0.393
BCF:   1.573
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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:   4.036
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.346
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.79
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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
NPO12298 Epilobium parviflorum Species Onagraceae Eukaryota n.a. n.a. n.a. PMID[37111814]
NPO8300 Apis mellifera ligustica Species Apidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8300 Apis mellifera ligustica Species Apidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12298 Epilobium parviflorum Species Onagraceae 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
NPO12298 Epilobium parviflorum n.a. n.a. 48.63 ± 0.03 n.a. n.a. μg/g PMID[37111814]

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
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 5011.9 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 = 35700.0 nM PMID[11720850]
NPT71 Cell line HEK293 Homo sapiens FC = 3.6 n.a. PMID[19307119]
NPT2 Others Unspecified n.a. Potency = 14125.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Inhibition = 108.3 % PMID[21907578]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus Protection = 32.0 % DOI[10.1016/0960-894X(96)00134-5]





 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 NPC228184 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
0.6977 Remote Similarity NPC265871
0.6977 Remote Similarity NPC205093
0.675 Remote Similarity NPC314329
0.675 Remote Similarity NPC603208
0.6444 Remote Similarity NPC22467
0.6364 Remote Similarity NPC485642
0.6364 Remote Similarity NPC611561
0.6279 Remote Similarity NPC99854
0.617 Remote Similarity NPC177354
0.5833 Remote Similarity NPC150648
0.5745 Remote Similarity NPC225153
0.5745 Remote Similarity NPC188243
0.5745 Remote Similarity NPC479876
0.5745 Remote Similarity NPC110228
0.5714 Remote Similarity NPC99597
0.5714 Remote Similarity NPC255106
0.5714 Remote Similarity NPC235165
0.56 Remote Similarity NPC476153
0.5577 Remote Similarity NPC259685
0.5532 Remote Similarity NPC135616
0.551 Remote Similarity NPC37392
0.5417 Remote Similarity NPC476480
0.5417 Remote Similarity NPC84585
0.54 Remote Similarity NPC194432
0.5306 Remote Similarity NPC243083
0.5306 Remote Similarity NPC13768
0.5306 Remote Similarity NPC287246
0.5306 Remote Similarity NPC204515
0.5306 Remote Similarity NPC482487
0.5273 Remote Similarity NPC87486
0.5273 Remote Similarity NPC124780
0.5273 Remote Similarity NPC608647
0.52 Remote Similarity NPC312391
0.5098 Remote Similarity NPC482119
0.5098 Remote Similarity NPC482120
0.5098 Remote Similarity NPC215885
0.5098 Remote Similarity NPC156057
0.5098 Remote Similarity NPC110038

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC228184 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
0.675 Remote Similarity NPD1547 Clinical (unspecified phase)
0.5306 Remote Similarity NPD1550 Phase 2

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