Natural Product: NPC303185

Natural Product IDNPC303185
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3R,3S)-Vestitone
IUPAC Name 7-hydroxy-3-(2-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms (3R,3S)-Vestitone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1087009
PubChem CID 171769
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids

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 WQCJOKYOIJVEFN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O5/c1-20-10-3-5-11(14(18)7-10)13-8-21-15-6-9(17)2-4-12(15)16(13)19/h2-7,13,17-18H,8H2,1H3
SMILES COc1ccc(C2COc3cc(ccc3C2=O)O)c(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   285.119
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Van der Waals volume.
Dense:   1.003 LogP:   2.532
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.727
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.871
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.887 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.834 Fsp3:   0.188
MCE-18:   54.579
?
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:   0.277 Fluc inhibitor:   0.89
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.242
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.4
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.428 Promiscuous compounds:   0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.843 MDCK Permeability:   -4.781
Pgp-inhibitor:   0.003 Pgp-substrate:   0.011
PAMPA:   0.425
?
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):   0.016
20% Bioavailability (F20%):   0.177 30% Bioavailability (F30%):   0.119
50% Bioavailability (F50%):   0.833

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.487
Plasma Protein Binding (PPB):   91.363% Volume Distribution (VD):   -0.248
Fu: 9.773%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.934
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.141
BSEP inhibitor:   0.421

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.153
CYP2C19-inhibitor:   0.99 CYP2C19-substrate:   0.427
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   0.285
CYP2D6-inhibitor:   0.961 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.103 CYP3A4-substrate:   0.009
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.521
HLM stability:   0.298
?
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):  4.321 Half-life (T1/2):  1.879

ADMET: Toxicity

hERG Blockers:  0.173 hERG Blockers (10um):  0.627
Human Hepatotoxicity (H-HT):  0.552 Drug-induced Liver Injury (DILI):  0.371
AMES Toxicity:  0.613 Rat Oral Acute Toxicity:  0.454
Maximum Recommended Daily Dose:  0.457 Skin Sensitization:  0.505
Carcinogencity:  0.79 Eye Corrosion:  0.027
Eye Irritation:  0.897 Respiratory Toxicity:  0.804
Drug-induced Neurotoxicity:  0.241 Ototoxicity:  0.291
Hematotoxicity:  0.194 Drug-induced Nephrotoxicity:  0.213
Genotoxicity:  0.595 RPMI-8226 Immunitoxicity:  0.053
A549 Cytotoxicity:  0.417 Hek293 Cytotoxicity:  0.645
BCF:   1.2
?
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:   3.683
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.405
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.937
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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
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[19928832]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23743282]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9525107]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30034 Onobrychis vicllfolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14114 Dalbergia parviflora Species Fabaceae 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
NPT396 Cell line T47D Homo sapiens Activity > 100.0 uM PMID[19928832]
NPT396 Cell line T47D Homo sapiens Activity = 7.3 uM PMID[19928832]
NPT83 Cell line MCF7 Homo sapiens Activity > 100.0 uM PMID[19928832]
NPT396 Cell line T47D Homo sapiens Activity = 33.7 uM PMID[19928832]
NPT396 Cell line T47D Homo sapiens Activity = 1.5 uM PMID[19928832]
NPT83 Cell line MCF7 Homo sapiens Activity = 45.3 uM PMID[19928832]
NPT83 Cell line MCF7 Homo sapiens Activity = 5.7 uM PMID[19928832]

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 NPC303185 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
1.0 High Similarity NPC184649
1.0 High Similarity NPC133501
0.7551 Intermediate Similarity NPC202981
0.7551 Intermediate Similarity NPC488571
0.7115 Intermediate Similarity NPC299011
0.6923 Remote Similarity NPC113770
0.6667 Remote Similarity NPC488568
0.6604 Remote Similarity NPC255807
0.6604 Remote Similarity NPC31018
0.6604 Remote Similarity NPC469550
0.6481 Remote Similarity NPC129684
0.6481 Remote Similarity NPC299520
0.6481 Remote Similarity NPC181960
0.6 Remote Similarity NPC230479
0.6 Remote Similarity NPC50315
0.5902 Remote Similarity NPC482703
0.5893 Remote Similarity NPC311144
0.5714 Remote Similarity NPC267117
0.5345 Remote Similarity NPC188947

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC303185 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