Natural Product: NPC469764

Natural Product IDNPC469764
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Methyl Naringenin
IUPAC Name (2S)-7-acetyl-5-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one
Synonyms 7-O-Methyl Naringenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1170808
PubChem CID 49798152
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones

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 MJDZZDSZRFXPRN-HNNXBMFYSA-N
Standard InCHI InChI=1S/C17H14O5/c1-9(18)11-6-13(20)17-14(21)8-15(22-16(17)7-11)10-2-4-12(19)5-3-10/h2-7,15,19-20H,8H2,1H3/t15-/m0/s1
SMILES Oc1ccc(cc1)[C@@H]1CC(=O)c2c(O1)cc(cc2O)C(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.08 Volume:   299.778
?
Van der Waals volume.
Dense:   0.994 LogP:   2.514
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.752
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.052
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   83.83
?
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:   0.833 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.818 Fsp3:   0.176
MCE-18:   57.6
?
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:   0.623 Fluc inhibitor:   0.664
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.357
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.33
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.368 Promiscuous compounds:   0.153

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.855 MDCK Permeability:   -4.721
Pgp-inhibitor:   0.889 Pgp-substrate:   0.265
PAMPA:   0.345
?
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%):   0.21
50% Bioavailability (F50%):   0.916

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.972
Plasma Protein Binding (PPB):   93.074% Volume Distribution (VD):   -0.02
Fu: 8.788%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.721
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.974
BSEP inhibitor:   0.925

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.985
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.99
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.036
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.255
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.986
HLM stability:   0.675
?
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):  7.29 Half-life (T1/2):  1.064

ADMET: Toxicity

hERG Blockers:  0.126 hERG Blockers (10um):  0.429
Human Hepatotoxicity (H-HT):  0.804 Drug-induced Liver Injury (DILI):  0.616
AMES Toxicity:  0.712 Rat Oral Acute Toxicity:  0.65
Maximum Recommended Daily Dose:  0.718 Skin Sensitization:  0.828
Carcinogencity:  0.469 Eye Corrosion:  0.059
Eye Irritation:  0.989 Respiratory Toxicity:  0.884
Drug-induced Neurotoxicity:  0.812 Ototoxicity:  0.402
Hematotoxicity:  0.299 Drug-induced Nephrotoxicity:  0.643
Genotoxicity:  0.987 RPMI-8226 Immunitoxicity:  0.155
A549 Cytotoxicity:  0.636 Hek293 Cytotoxicity:  0.594
BCF:   1.028
?
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:   3.549
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.471
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.952
?
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
NPO23852 Cryptocarya obovata Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[15165150]
NPO23852 Cryptocarya obovata Species Lauraceae Eukaryota n.a. trunk bark n.a. PMID[15165150]
NPO23852 Cryptocarya obovata Species Lauraceae Eukaryota n.a. fruit n.a. PMID[15165150]
NPO23852 Cryptocarya obovata Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[20558060]
NPO23852 Cryptocarya obovata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23852 Cryptocarya obovata Species Lauraceae 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
NPT71 Cell line HEK293 Homo sapiens IC50 > 167000.0 nM PMID[22194678]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 > 167000.0 nM PMID[23313635]

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 NPC469764 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
0.78 Intermediate Similarity NPC469758
0.6667 Remote Similarity NPC32441
0.6667 Remote Similarity NPC79943
0.6415 Remote Similarity NPC329203
0.6415 Remote Similarity NPC222342
0.6111 Remote Similarity NPC324386
0.5818 Remote Similarity NPC300668
0.5769 Remote Similarity NPC329225
0.5769 Remote Similarity NPC147686
0.5741 Remote Similarity NPC603284
0.5714 Remote Similarity NPC321011
0.5714 Remote Similarity NPC294852
0.5714 Remote Similarity NPC188679
0.5714 Remote Similarity NPC475267
0.5714 Remote Similarity NPC606248
0.5574 Remote Similarity NPC69674
0.5556 Remote Similarity NPC225153
0.5556 Remote Similarity NPC479876
0.5484 Remote Similarity NPC220998
0.5484 Remote Similarity NPC470135
0.5455 Remote Similarity NPC243083
0.5455 Remote Similarity NPC13768
0.5455 Remote Similarity NPC287246
0.5439 Remote Similarity NPC210084
0.541 Remote Similarity NPC107572
0.541 Remote Similarity NPC39329
0.541 Remote Similarity NPC32739
0.541 Remote Similarity NPC51032
0.5397 Remote Similarity NPC486094
0.5357 Remote Similarity NPC167624
0.5357 Remote Similarity NPC166482
0.5333 Remote Similarity NPC236637
0.5323 Remote Similarity NPC477841
0.5303 Remote Similarity NPC611447
0.5273 Remote Similarity NPC182421
0.5263 Remote Similarity NPC274784
0.5263 Remote Similarity NPC20709
0.5246 Remote Similarity NPC169591
0.5246 Remote Similarity NPC480991
0.5246 Remote Similarity NPC298223
0.5246 Remote Similarity NPC604412
0.5238 Remote Similarity NPC109223
0.5238 Remote Similarity NPC470131
0.5238 Remote Similarity NPC470132
0.5238 Remote Similarity NPC10937
0.5179 Remote Similarity NPC295261
0.5179 Remote Similarity NPC296490
0.5179 Remote Similarity NPC6407
0.5179 Remote Similarity NPC545184
0.5172 Remote Similarity NPC485881
0.5156 Remote Similarity NPC134171
0.5147 Remote Similarity NPC228504
0.5088 Remote Similarity NPC1612
0.5088 Remote Similarity NPC150648
0.5088 Remote Similarity NPC183959
0.5079 Remote Similarity NPC265040
0.5072 Remote Similarity NPC472629

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC469764 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
0.6667 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5769 Remote Similarity NPD1549 Phase 2
0.5455 Remote Similarity NPD1550 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