Natural Product: NPC93398

Natural Product IDNPC93398
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7,4'-Dihydroxyflavan
IUPAC Name 2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-7-ol
Synonyms 7,4'-Dihydroxyflavan
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL508033
PubChem CID 3500616
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002991] Hydroxyflavonoids
          • [CHEMONTID:0002993] 7-hydroxyflavonoids

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 YXMLGIGHGPSEKA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O3/c16-12-5-1-10(2-6-12)14-8-4-11-3-7-13(17)9-15(11)18-14/h1-3,5-7,9,14,16-17H,4,8H2
SMILES Oc1ccc(cc1)C1CCc2c(O1)cc(cc2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   242.09 Volume:   252.879
?
Van der Waals volume.
Dense:   0.957 LogP:   2.854
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.824
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.371
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   49.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.807 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.621 Fsp3:   0.2
MCE-18:   50.0
?
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:   0.584 Fluc inhibitor:   0.877
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.037
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.21
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.638 Promiscuous compounds:   0.159

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.767 MDCK Permeability:   -4.768
Pgp-inhibitor:   0.065 Pgp-substrate:   0.498
PAMPA:   0.084
?
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%):   0.073 30% Bioavailability (F30%):   0.373
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.061 MRP1:   0.897
Plasma Protein Binding (PPB):   94.463% Volume Distribution (VD):   0.251
Fu: 6.623%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.75
OATP1B3 inhibitor:   0.973 BCRP inhibitor:   0.922
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.266 CYP1A2-substrate:   0.315
CYP2C19-inhibitor:   0.168 CYP2C19-substrate:   0.8
CYP2C9-inhibitor:   0.397 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.29
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.14
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.494
HLM stability:   0.49
?
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):  7.688 Half-life (T1/2):  1.56

ADMET: Toxicity

hERG Blockers:  0.572 hERG Blockers (10um):  0.775
Human Hepatotoxicity (H-HT):  0.7 Drug-induced Liver Injury (DILI):  0.035
AMES Toxicity:  0.389 Rat Oral Acute Toxicity:  0.496
Maximum Recommended Daily Dose:  0.824 Skin Sensitization:  0.414
Carcinogencity:  0.593 Eye Corrosion:  0.006
Eye Irritation:  0.881 Respiratory Toxicity:  0.547
Drug-induced Neurotoxicity:  0.537 Ototoxicity:  0.345
Hematotoxicity:  0.079 Drug-induced Nephrotoxicity:  0.218
Genotoxicity:  0.681 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.312 Hek293 Cytotoxicity:  0.823
BCF:   1.378
?
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:   3.835
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.432
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.204
?
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]
NPO16111 Broussonetia kazinoki Species Moraceae Eukaryota Leaves n.a. n.a. PMID[11575957]
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]
NPO16111 Broussonetia kazinoki Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19046886]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota Fruits n.a. n.a. PMID[19296617]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[1955887]
NPO16111 Broussonetia kazinoki Species Moraceae Eukaryota n.a. n.a. n.a. PMID[20493686]
NPO33390 broussonetia kanzinoki Species Moraceae Eukaryota n.a. n.a. n.a. PMID[22450131]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[2878063]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[7130988]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota bark n.a. n.a. PMID[7623034]
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]
NPO16111 Broussonetia kazinoki Species Moraceae Eukaryota n.a. n.a. n.a. PMID[9917310]
NPO16111 Broussonetia kazinoki Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5495 Broussonetia papyrifera Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16111 Broussonetia kazinoki Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27064 Taxus brevifolia Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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]
NPO16111 Broussonetia kazinoki 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]
NPO27064 Taxus brevifolia Species Taxaceae 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
NPT3172 Individual protein Phospholipase A2 group IIA Homo sapiens IC50 > 3300.0 nM PMID[18818074]
NPT1120 Individual protein Pancreatic triacylglycerol lipase Sus scrofa Inhibition = 55.6 % PMID[22450131]
NPT1120 Individual protein Pancreatic triacylglycerol lipase Sus scrofa IC50 = 85100.0 nM PMID[22450131]
NPT4062 Individual protein Phospholipase A2 group IIA Rattus norvegicus IC50 > 3300.0 nM PMID[18818074]
NPT4061 Individual protein Phospholipase A2, membrane associated Mus musculus IC50 > 3300.0 nM PMID[18818074]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2428 Cell line HT-3 Homo sapiens ED50 = 11.6 ug ml-1 PMID[9917310]
NPT2245 Cell line SiHa Homo sapiens ED50 = 8.9 ug ml-1 PMID[9917310]
NPT2306 Cell line Ca-Ski Homo sapiens ED50 = 17.4 ug ml-1 PMID[9917310]

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 NPC93398 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 NPC258979
1.0 High Similarity NPC8283
0.7907 Intermediate Similarity NPC36016
0.7021 Intermediate Similarity NPC470356
0.68 Remote Similarity NPC197351
0.6739 Remote Similarity NPC100099
0.6667 Remote Similarity NPC482472
0.66 Remote Similarity NPC292487
0.6444 Remote Similarity NPC106914
0.6444 Remote Similarity NPC86502
0.6226 Remote Similarity NPC481762
0.6226 Remote Similarity NPC481761
0.6111 Remote Similarity NPC473413
0.5957 Remote Similarity NPC76465
0.5918 Remote Similarity NPC134195
0.5862 Remote Similarity NPC471522
0.5778 Remote Similarity NPC85292
0.5745 Remote Similarity NPC329225
0.5745 Remote Similarity NPC147686
0.5636 Remote Similarity NPC481767
0.5636 Remote Similarity NPC234952
0.5636 Remote Similarity NPC481770
0.5636 Remote Similarity NPC481769
0.5636 Remote Similarity NPC481768
0.5636 Remote Similarity NPC481771
0.5625 Remote Similarity NPC601844
0.56 Remote Similarity NPC188022
0.5536 Remote Similarity NPC265075
0.5517 Remote Similarity NPC481764
0.5517 Remote Similarity NPC481766
0.5517 Remote Similarity NPC481765
0.549 Remote Similarity NPC17809
0.5472 Remote Similarity NPC246648
0.5417 Remote Similarity NPC309717
0.5345 Remote Similarity NPC32630
0.52 Remote Similarity NPC225153
0.52 Remote Similarity NPC479876
0.5111 Remote Similarity NPC486692
0.5098 Remote Similarity NPC32441
0.5098 Remote Similarity NPC79943
0.5088 Remote Similarity NPC149796

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC93398 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
0.5745 Remote Similarity NPD1549 Phase 2
0.5098 Remote Similarity NPD1552 Clinical (unspecified phase)

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