Natural Product: NPC472912

Natural Product IDNPC472912
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-Dihydroxy-3-(3'-Hydroxy-4'-Methoxybenzyl)-4-Chromanone
IUPAC Name (3R)-5,7-dihydroxy-3-[(3-hydroxy-4-methoxyphenyl)methyl]-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3594087
PubChem CID 638295
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002507] Homoisoflavonoids
        • [CHEMONTID:0002508] Homoisoflavans
          • [CHEMONTID:0002898] Homoisoflavanones

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 WIBOONWRYQFYQJ-SNVBAGLBSA-N
Standard InCHI InChI=1S/C17H16O6/c1-22-14-3-2-9(5-12(14)19)4-10-8-23-15-7-11(18)6-13(20)16(15)17(10)21/h2-3,5-7,10,18-20H,4,8H2,1H3/t10-/m1/s1
SMILES COc1ccc(cc1O)C[C@@H]1COc2c(C1=O)c(O)cc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.09 Volume:   311.205
?
Van der Waals volume.
Dense:   1.016 LogP:   2.046
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.265
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.613
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.803 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.01 Fsp3:   0.235
MCE-18:   57.429
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.357 Fluc inhibitor:   0.591
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.146
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.348
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.318 Promiscuous compounds:   0.479

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.098 MDCK Permeability:   -4.824
Pgp-inhibitor:   0.104 Pgp-substrate:   0.251
PAMPA:   0.19
?
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):   0.0
20% Bioavailability (F20%):   0.192 30% Bioavailability (F30%):   0.326
50% Bioavailability (F50%):   0.398

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.644
Plasma Protein Binding (PPB):   97.268% Volume Distribution (VD):   -0.399
Fu: 2.198%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.156
OATP1B3 inhibitor:   0.239 BCRP inhibitor:   0.306
BSEP inhibitor:   0.593

ADMET: Metabolism

CYP1A2-inhibitor:   0.991 CYP1A2-substrate:   0.934
CYP2C19-inhibitor:   0.172 CYP2C19-substrate:   0.981
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.975
CYP2D6-inhibitor:   0.969 CYP2D6-substrate:   0.97
CYP3A4-inhibitor:   0.988 CYP3A4-substrate:   0.729
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.99
?
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):  5.268 Half-life (T1/2):  1.415

ADMET: Toxicity

hERG Blockers:  0.131 hERG Blockers (10um):  0.552
Human Hepatotoxicity (H-HT):  0.785 Drug-induced Liver Injury (DILI):  0.875
AMES Toxicity:  0.772 Rat Oral Acute Toxicity:  0.585
Maximum Recommended Daily Dose:  0.612 Skin Sensitization:  0.947
Carcinogencity:  0.524 Eye Corrosion:  0.007
Eye Irritation:  0.987 Respiratory Toxicity:  0.938
Drug-induced Neurotoxicity:  0.693 Ototoxicity:  0.496
Hematotoxicity:  0.28 Drug-induced Nephrotoxicity:  0.659
Genotoxicity:  0.996 RPMI-8226 Immunitoxicity:  0.205
A549 Cytotoxicity:  0.85 Hek293 Cytotoxicity:  0.829
BCF:   1.222
?
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:   3.767
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.041
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.289
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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
NPO33045 bellevalia eigii Species Hyacinthaceae Eukaryota Bulbs Irbid, Jordan n.a. PMID[26147490]
NPO33045 bellevalia eigii Species Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT139 Cell line HT-29 Homo sapiens ED50 = 1.33 uM PMID[23944995]
NPT400 Cell line MDA-MB-435 Homo sapiens ED50 = 2.78 uM PMID[23944995]
NPT139 Cell line HT-29 Homo sapiens IC50 > 20000.0 nM PMID[19879150]
NPT400 Cell line MDA-MB-435 Homo sapiens IC50 = 1000.0 nM PMID[19879150]
NPT21 Organism Aspergillus niger Aspergillus niger MIC > 138.0 ug.mL-1 PMID[16872137]
NPT20 Organism Candida albicans Candida albicans MIC > 138.0 ug.mL-1 DrugMatrix in vitro pharmacology data
NPT602 Organism Mycobacterium smegmatis Mycobacterium smegmatis MIC = 17.0 ug.mL-1 DrugMatrix in vitro pharmacology data
NPT19 Organism Escherichia coli Escherichia coli MIC > 138.0 ug.mL-1 PMID[16643028]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 138.0 ug.mL-1 PMID[16643028]

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 NPC472912 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
0.7925 Intermediate Similarity NPC129853
0.7925 Intermediate Similarity NPC76445
0.7455 Intermediate Similarity NPC3036
0.7321 Intermediate Similarity NPC222814
0.7222 Intermediate Similarity NPC118813
0.7018 Intermediate Similarity NPC472914
0.6613 Remote Similarity NPC482961
0.6167 Remote Similarity NPC482972
0.6167 Remote Similarity NPC482974
0.5833 Remote Similarity NPC284550
0.5806 Remote Similarity NPC482968
0.5781 Remote Similarity NPC482962
0.5738 Remote Similarity NPC96167
0.5574 Remote Similarity NPC482966
0.5574 Remote Similarity NPC235640
0.5484 Remote Similarity NPC472910
0.5484 Remote Similarity NPC269176
0.541 Remote Similarity NPC260979
0.5397 Remote Similarity NPC472911
0.5333 Remote Similarity NPC170468
0.5323 Remote Similarity NPC472909
0.5238 Remote Similarity NPC245758
0.5161 Remote Similarity NPC105512
0.5094 Remote Similarity NPC212379
0.5079 Remote Similarity NPC482973

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472912 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