Natural Product: NPC568297

Natural Product IDNPC568297
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-8-methoxy-2-phenyl-chroman-4-one
IUPAC Name (2~{R})-5,7-dihydroxy-8-methoxy-2-phenyl-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 FKAOWOSRYSMEBS-CYBMUJFWSA-N
Standard InCHI InChI=1S/C16H14O5/c1-20-15-12(19)7-10(17)14-11(18)8-13(21-16(14)15)9-5-3-2-4-6-9/h2-7,13,17,19H,8H2,1H3/t13-/m1/s1
SMILES COC1=C(O)C=C(O)C2=C1O[C@@H](C1=CC=CC=C1)CC2=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:   3.112
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.027
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.586
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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:   2.866 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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.493 Fluc inhibitor:   0.748
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.318
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.293
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.358 Promiscuous compounds:   0.053

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.96 MDCK Permeability:   -4.782
Pgp-inhibitor:   0.995 Pgp-substrate:   0.034
PAMPA:   0.251
?
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%):   0.001 30% Bioavailability (F30%):   0.4
50% Bioavailability (F50%):   0.926

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.47 MRP1:   0.943
Plasma Protein Binding (PPB):   98.106% Volume Distribution (VD):   0.126
Fu: 1.587%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.99
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.358 CYP1A2-substrate:   0.995
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.976
CYP2C9-inhibitor:   0.032 CYP2C9-substrate:   0.025
CYP2D6-inhibitor:   0.017 CYP2D6-substrate:   0.722
CYP3A4-inhibitor:   0.065 CYP3A4-substrate:   0.923
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.922
HLM stability:   0.995
?
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):  2.623 Half-life (T1/2):  1.298

ADMET: Toxicity

hERG Blockers:  0.086 hERG Blockers (10um):  0.476
Human Hepatotoxicity (H-HT):  0.767 Drug-induced Liver Injury (DILI):  0.272
AMES Toxicity:  0.686 Rat Oral Acute Toxicity:  0.531
Maximum Recommended Daily Dose:  0.476 Skin Sensitization:  0.835
Carcinogencity:  0.396 Eye Corrosion:  0.028
Eye Irritation:  0.99 Respiratory Toxicity:  0.189
Drug-induced Neurotoxicity:  0.838 Ototoxicity:  0.377
Hematotoxicity:  0.26 Drug-induced Nephrotoxicity:  0.765
Genotoxicity:  0.749 RPMI-8226 Immunitoxicity:  0.166
A549 Cytotoxicity:  0.409 Hek293 Cytotoxicity:  0.374
BCF:   1.394
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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:   3.964
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.444
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.608
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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
NPO15336 Prunus avium Species Rosaceae Eukaryota Fruit n.a. n.a. DOI[10.1016/j.foodchem.2007.08.004]
NPO15336 Prunus avium Species Rosaceae Eukaryota n.a. fruit n.a. DOI[10.1016/j.phytochem.2007.01.008]
NPO15336 Prunus avium Species Rosaceae Eukaryota n.a. fruit n.a. PMID[17328933]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[9917288]
NPO59261 Helichrysum glaciale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17726 Helichrysum cymosum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15336 Prunus avium Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO15336 Prunus avium Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO15336 Prunus avium Species Rosaceae Eukaryota Fruits n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruits n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO15336 Prunus avium Species Rosaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO15336 Prunus avium Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17726 Helichrysum cymosum 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 NPC568297 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
0.7 Intermediate Similarity NPC37392
0.6275 Remote Similarity NPC213322
0.6154 Remote Similarity NPC243083
0.6154 Remote Similarity NPC13768
0.6154 Remote Similarity NPC482121
0.6154 Remote Similarity NPC287246
0.6154 Remote Similarity NPC482487
0.6154 Remote Similarity NPC270964
0.6111 Remote Similarity NPC481903
0.6038 Remote Similarity NPC150648
0.5932 Remote Similarity NPC95936
0.5926 Remote Similarity NPC255106
0.5926 Remote Similarity NPC194432
0.5926 Remote Similarity NPC235165
0.5636 Remote Similarity NPC215885
0.5636 Remote Similarity NPC110038
0.5472 Remote Similarity NPC265871
0.5472 Remote Similarity NPC205093
0.5455 Remote Similarity NPC20354
0.5455 Remote Similarity NPC312391
0.5455 Remote Similarity NPC177354
0.5455 Remote Similarity NPC162869
0.5439 Remote Similarity NPC2416
0.5357 Remote Similarity NPC274784
0.5357 Remote Similarity NPC99597
0.5357 Remote Similarity NPC482119
0.5357 Remote Similarity NPC20709
0.5357 Remote Similarity NPC482120
0.5333 Remote Similarity NPC76372
0.5333 Remote Similarity NPC37496
0.5273 Remote Similarity NPC248372
0.5273 Remote Similarity NPC204515
0.5246 Remote Similarity NPC109183
0.5172 Remote Similarity NPC271590
0.5161 Remote Similarity NPC175504
0.5161 Remote Similarity NPC3642
0.5143 Remote Similarity NPC181014
0.5098 Remote Similarity NPC228184
0.5088 Remote Similarity NPC110776
0.5088 Remote Similarity NPC610021
0.5085 Remote Similarity NPC302950

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC568297 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
0.6154 Remote Similarity NPD1550 Phase 2
0.5085 Remote Similarity NPD1934 Phase 0

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