Natural Product: NPC230285

Natural Product IDNPC230285
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-Hydroxy-3,5-Dimethoxy-2-Phenylchromen-4-One
IUPAC Name 7-hydroxy-3,5-dimethoxy-2-phenylchromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL183723
PubChem CID 44392177
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 BUNIGAWIPPRWMH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O5/c1-20-12-8-11(18)9-13-14(12)15(19)17(21-2)16(22-13)10-6-4-3-5-7-10/h3-9,18H,1-2H3
SMILES COc1cc(cc2c1c(=O)c(c(c1ccccc1)o2)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.08 Volume:   299.778
?
Van der Waals volume.
Dense:   0.994 LogP:   2.823
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.817
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.302
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.804 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.171 Fsp3:   0.118
MCE-18:   17.0
?
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:   0
Colloidal aggregators:   0.155 Fluc inhibitor:   0.466
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.778
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.653
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.363 Promiscuous compounds:   0.385

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.805 MDCK Permeability:   -4.7
Pgp-inhibitor:   0.969 Pgp-substrate:   0.058
PAMPA:   0.279
?
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):   0.002
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.05
50% Bioavailability (F50%):   0.89

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.318 MRP1:   0.912
Plasma Protein Binding (PPB):   97.597% Volume Distribution (VD):   0.029
Fu: 2.003%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.006
OATP1B3 inhibitor:   0.505 BCRP inhibitor:   0.561
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.875 CYP1A2-substrate:   0.121
CYP2C19-inhibitor:   0.56 CYP2C19-substrate:   0.726
CYP2C9-inhibitor:   0.23 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   0.601 CYP2D6-substrate:   0.677
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.006
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.915
HLM stability:   0.312
?
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):  5.715 Half-life (T1/2):  0.881

ADMET: Toxicity

hERG Blockers:  0.136 hERG Blockers (10um):  0.529
Human Hepatotoxicity (H-HT):  0.475 Drug-induced Liver Injury (DILI):  0.816
AMES Toxicity:  0.544 Rat Oral Acute Toxicity:  0.43
Maximum Recommended Daily Dose:  0.684 Skin Sensitization:  0.494
Carcinogencity:  0.826 Eye Corrosion:  0.539
Eye Irritation:  0.984 Respiratory Toxicity:  0.596
Drug-induced Neurotoxicity:  0.229 Ototoxicity:  0.093
Hematotoxicity:  0.186 Drug-induced Nephrotoxicity:  0.073
Genotoxicity:  0.818 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.137 Hek293 Cytotoxicity:  0.47
BCF:   1.267
?
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:   4.046
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.848
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.47
?
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
NPO33252 heliotropium sinuatum Species Heliotropiaceae Eukaryota resinous exudate n.a. n.a. PMID[15603945]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[19615910]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[29323912]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23911 Alpinia officinarum Species Zingiberaceae 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
NPT610 Others Molecular identity unknown n.a. Ratio = 6.8 n.a. PMID[15603945]

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 NPC230285 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
0.8776 High Similarity NPC470216
0.7647 Intermediate Similarity NPC149127
0.7222 Intermediate Similarity NPC236223
0.7115 Intermediate Similarity NPC194281
0.6792 Remote Similarity NPC184536
0.6346 Remote Similarity NPC61546
0.6182 Remote Similarity NPC103904
0.5893 Remote Similarity NPC43243
0.5893 Remote Similarity NPC90582
0.5893 Remote Similarity NPC47815
0.5789 Remote Similarity NPC270465
0.5714 Remote Similarity NPC136840
0.569 Remote Similarity NPC605047
0.5614 Remote Similarity NPC189960
0.5614 Remote Similarity NPC103342
0.5593 Remote Similarity NPC50728
0.5517 Remote Similarity NPC59951
0.55 Remote Similarity NPC287101
0.5439 Remote Similarity NPC245546
0.541 Remote Similarity NPC604021
0.5357 Remote Similarity NPC608197
0.5345 Remote Similarity NPC266960
0.5345 Remote Similarity NPC292107
0.5254 Remote Similarity NPC286342
0.5254 Remote Similarity NPC260895
0.5254 Remote Similarity NPC146679
0.5205 Remote Similarity NPC599850
0.5179 Remote Similarity NPC72452
0.5085 Remote Similarity NPC203891
0.5085 Remote Similarity NPC123886
0.5085 Remote Similarity NPC262094
0.5085 Remote Similarity NPC609062
0.5082 Remote Similarity NPC82325
0.5082 Remote Similarity NPC605582

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC230285 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