Natural Product: NPC563730

Natural Product IDNPC563730
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R})-5,7-dihydroxy-2-(3-hydroxyphenyl)chroman-4-one
IUPAC Name (2~{R})-5,7-dihydroxy-2-(3-hydroxyphenyl)chroman-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 NJWJQMLMBXIOJW-CYBMUJFWSA-N
Standard InCHI InChI=1S/C15H12O5/c16-9-3-1-2-8(4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-6,13,16-18H,7H2/t13-/m1/s1
SMILES O=C1C[C@H](C2=CC=CC(O)=C2)OC2=CC(O)=CC(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.07 Volume:   267.823
?
Van der Waals volume.
Dense:   1.016 LogP:   2.634
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.792
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.76
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.742 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.894 Fsp3:   0.133
MCE-18:   55.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.601 Fluc inhibitor:   0.757
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.29
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.212
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.502 Promiscuous compounds:   0.078

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.934 MDCK Permeability:   -4.762
Pgp-inhibitor:   0.227 Pgp-substrate:   0.039
PAMPA:   0.267
?
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%):   0.153 30% Bioavailability (F30%):   0.919
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.762
Plasma Protein Binding (PPB):   93.106% Volume Distribution (VD):   -0.411
Fu: 9.882%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.945
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.955
BSEP inhibitor:   0.501

ADMET: Metabolism

CYP1A2-inhibitor:   0.414 CYP1A2-substrate:   0.992
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.973
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.893
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):  7.49 Half-life (T1/2):  1.186

ADMET: Toxicity

hERG Blockers:  0.109 hERG Blockers (10um):  0.515
Human Hepatotoxicity (H-HT):  0.69 Drug-induced Liver Injury (DILI):  0.606
AMES Toxicity:  0.745 Rat Oral Acute Toxicity:  0.722
Maximum Recommended Daily Dose:  0.85 Skin Sensitization:  0.841
Carcinogencity:  0.634 Eye Corrosion:  0.108
Eye Irritation:  0.995 Respiratory Toxicity:  0.909
Drug-induced Neurotoxicity:  0.591 Ototoxicity:  0.255
Hematotoxicity:  0.111 Drug-induced Nephrotoxicity:  0.431
Genotoxicity:  0.993 RPMI-8226 Immunitoxicity:  0.11
A549 Cytotoxicity:  0.712 Hek293 Cytotoxicity:  0.761
BCF:   1.312
?
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:   3.687
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.632
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.003
?
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
NPO2186 Encelia stenophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2186 Encelia stenophylla Species Asteraceae 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

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 NPC563730 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
0.8085 Intermediate Similarity NPC243083
0.8085 Intermediate Similarity NPC13768
0.8085 Intermediate Similarity NPC287246
0.7959 Intermediate Similarity NPC321011
0.7959 Intermediate Similarity NPC294852
0.7959 Intermediate Similarity NPC188679
0.7872 Intermediate Similarity NPC182421
0.7708 Intermediate Similarity NPC32441
0.7708 Intermediate Similarity NPC79943
0.7308 Intermediate Similarity NPC302950
0.7059 Intermediate Similarity NPC274784
0.7059 Intermediate Similarity NPC20709
0.7059 Intermediate Similarity NPC107586
0.7 Intermediate Similarity NPC295261
0.7 Intermediate Similarity NPC296490
0.7 Intermediate Similarity NPC12296
0.6731 Remote Similarity NPC338131
0.6727 Remote Similarity NPC236637
0.6379 Remote Similarity NPC477841
0.6271 Remote Similarity NPC109223
0.6271 Remote Similarity NPC10937
0.6034 Remote Similarity NPC258630
0.5902 Remote Similarity NPC106976
0.5873 Remote Similarity NPC312973
0.5818 Remote Similarity NPC73028
0.5806 Remote Similarity NPC108456
0.5806 Remote Similarity NPC174953
0.5781 Remote Similarity NPC611447
0.5741 Remote Similarity NPC264083
0.5738 Remote Similarity NPC17170
0.5714 Remote Similarity NPC134783
0.5692 Remote Similarity NPC118256
0.5636 Remote Similarity NPC150648
0.5636 Remote Similarity NPC312391
0.5625 Remote Similarity NPC470890
0.5625 Remote Similarity NPC475790
0.5606 Remote Similarity NPC474021
0.5556 Remote Similarity NPC476480
0.5556 Remote Similarity NPC84585
0.5538 Remote Similarity NPC473990
0.5536 Remote Similarity NPC482119
0.5536 Remote Similarity NPC482120
0.5536 Remote Similarity NPC329203
0.5536 Remote Similarity NPC324386
0.5536 Remote Similarity NPC222342
0.5455 Remote Similarity NPC204515
0.5441 Remote Similarity NPC224851
0.5441 Remote Similarity NPC474038
0.5439 Remote Similarity NPC469764
0.541 Remote Similarity NPC39045
0.5385 Remote Similarity NPC200761
0.5373 Remote Similarity NPC473272
0.537 Remote Similarity NPC265871
0.537 Remote Similarity NPC205093
0.5357 Remote Similarity NPC1612
0.5357 Remote Similarity NPC183959
0.5345 Remote Similarity NPC18727
0.5345 Remote Similarity NPC310135
0.5303 Remote Similarity NPC69531
0.5303 Remote Similarity NPC88964
0.5278 Remote Similarity NPC602605
0.5273 Remote Similarity NPC213322
0.5263 Remote Similarity NPC300668
0.5263 Remote Similarity NPC255106
0.5263 Remote Similarity NPC235165
0.5238 Remote Similarity NPC470135
0.5217 Remote Similarity NPC26195
0.5185 Remote Similarity NPC329225
0.5185 Remote Similarity NPC147686
0.5179 Remote Similarity NPC472460
0.5179 Remote Similarity NPC201227
0.5179 Remote Similarity NPC258474
0.5179 Remote Similarity NPC482121
0.5179 Remote Similarity NPC6407
0.5179 Remote Similarity NPC270964
0.5179 Remote Similarity NPC545184
0.5179 Remote Similarity NPC603284
0.5172 Remote Similarity NPC606248
0.5156 Remote Similarity NPC134171
0.5143 Remote Similarity NPC227579
0.5143 Remote Similarity NPC214166
0.5143 Remote Similarity NPC475784
0.5135 Remote Similarity NPC158188
0.5088 Remote Similarity NPC37392
0.5088 Remote Similarity NPC4152
0.5077 Remote Similarity NPC85121
0.507 Remote Similarity NPC74924
0.507 Remote Similarity NPC111786
0.5068 Remote Similarity NPC479054

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC563730 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
0.8085 Intermediate Similarity NPD1550 Phase 2
0.7708 Intermediate Similarity NPD1552 Clinical (unspecified phase)
0.7308 Intermediate Similarity NPD1934 Phase 0
0.5185 Remote Similarity NPD1549 Phase 2

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