Natural Product: NPC473413

Natural Product IDNPC473413
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-(7-Hydroxy-Chroman-2-Yl)-3-(3-Methyl-But-2-Enyl)-Benzene-1,2-Diol
IUPAC Name 5-(7-hydroxy-3,4-dihydro-2H-chromen-2-yl)-3-(3-methylbut-2-enyl)benzene-1,2-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL420310
PubChem CID 44342137
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003643] 3'-prenylated flavans

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 MSTNVJDHQJXVFI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H22O4/c1-12(2)3-4-14-9-15(10-17(22)20(14)23)18-8-6-13-5-7-16(21)11-19(13)24-18/h3,5,7,9-11,18,21-23H,4,6,8H2,1-2H3
SMILES CC(=CCc1cc(cc(c1O)O)C1CCc2c(O1)cc(cc2)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.15 Volume:   345.512
?
Van der Waals volume.
Dense:   0.944 LogP:   3.813
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.265
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.319
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   69.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.578 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.216 Fsp3:   0.3
MCE-18:   58.154
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.762 Fluc inhibitor:   0.592
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.052
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.286
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.418 Promiscuous compounds:   0.042

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.869 MDCK Permeability:   -4.778
Pgp-inhibitor:   0.013 Pgp-substrate:   0.018
PAMPA:   0.294
?
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%):   0.989 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.077 MRP1:   0.942
Plasma Protein Binding (PPB):   93.677% Volume Distribution (VD):   0.07
Fu: 8.937%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.812
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.992
BSEP inhibitor:   0.547

ADMET: Metabolism

CYP1A2-inhibitor:   0.426 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.992
CYP2C9-inhibitor:   0.032 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.182 CYP2D6-substrate:   0.034
CYP3A4-inhibitor:   0.994 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.991
?
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):  9.755 Half-life (T1/2):  1.766

ADMET: Toxicity

hERG Blockers:  0.318 hERG Blockers (10um):  0.736
Human Hepatotoxicity (H-HT):  0.699 Drug-induced Liver Injury (DILI):  0.133
AMES Toxicity:  0.467 Rat Oral Acute Toxicity:  0.741
Maximum Recommended Daily Dose:  0.817 Skin Sensitization:  0.784
Carcinogencity:  0.451 Eye Corrosion:  0.0
Eye Irritation:  0.412 Respiratory Toxicity:  0.834
Drug-induced Neurotoxicity:  0.448 Ototoxicity:  0.591
Hematotoxicity:  0.115 Drug-induced Nephrotoxicity:  0.31
Genotoxicity:  0.906 RPMI-8226 Immunitoxicity:  0.043
A549 Cytotoxicity:  0.571 Hek293 Cytotoxicity:  0.722
BCF:   1.796
?
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:   4.771
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.893
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.45
?
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
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. root n.a. PMID[11395279]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants Shawnee National Forest, Harrisburg, IL, US n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota whole plants n.a. n.a. PMID[11678652]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[12419367]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota leaves Kaohsiung, Taiwan 2006-SEP PMID[18986201]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota Fruits n.a. n.a. PMID[19296617]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. formosan n.a. PMID[8864236]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9358644]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5495 Broussonetia papyrifera Species Moraceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 41500.0 nM PMID[19769341]
NPT526 Individual protein Alpha-glucosidase MAL62 Saccharomyces cerevisiae logIC50 = 1.879 n.a. DOI[10.1007/s00044-011-9938-0]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC473413 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
0.7679 Intermediate Similarity NPC197351
0.7288 Intermediate Similarity NPC265075
0.6774 Remote Similarity NPC32630
0.6557 Remote Similarity NPC234952
0.6557 Remote Similarity NPC481770
0.6557 Remote Similarity NPC481771
0.6418 Remote Similarity NPC481758
0.6418 Remote Similarity NPC481759
0.6418 Remote Similarity NPC481760
0.6418 Remote Similarity NPC481756
0.6111 Remote Similarity NPC93398
0.6111 Remote Similarity NPC258979
0.6111 Remote Similarity NPC8283
0.6 Remote Similarity NPC106976
0.5873 Remote Similarity NPC482704
0.5862 Remote Similarity NPC36016
0.5857 Remote Similarity NPC481763
0.5833 Remote Similarity NPC470356
0.5694 Remote Similarity NPC474397
0.5694 Remote Similarity NPC481757
0.5625 Remote Similarity NPC143896
0.5556 Remote Similarity NPC131118
0.5538 Remote Similarity NPC481762
0.5538 Remote Similarity NPC481761
0.5479 Remote Similarity NPC233980
0.5479 Remote Similarity NPC481772
0.5479 Remote Similarity NPC197679
0.5455 Remote Similarity NPC221432
0.5455 Remote Similarity NPC257097
0.5373 Remote Similarity NPC15543
0.5312 Remote Similarity NPC292487
0.5156 Remote Similarity NPC246648
0.5147 Remote Similarity NPC68104
0.5075 Remote Similarity NPC481767
0.5075 Remote Similarity NPC481769
0.5075 Remote Similarity NPC481768
0.507 Remote Similarity NPC291508

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473413 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