Natural Product: NPC175504

Natural Product IDNPC175504
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-5-Hydroxy-7-Methoxy-8-[(E)-3-Oxo-1-Butenyl]Flavanone
IUPAC Name (2S)-5-hydroxy-7-methoxy-8-[(E)-3-oxobut-1-enyl]-2-phenyl-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL454068
PubChem CID 10980660
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 GAGKUHAKUBMORD-IJDCCNJMSA-N
Standard InCHI InChI=1S/C20H18O5/c1-12(21)8-9-14-18(24-2)11-16(23)19-15(22)10-17(25-20(14)19)13-6-4-3-5-7-13/h3-9,11,17,23H,10H2,1-2H3/b9-8+/t17-/m0/s1
SMILES COc1cc(O)c2c(c1/C=C/C(=O)C)O[C@@H](CC2=O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.12 Volume:   349.03
?
Van der Waals volume.
Dense:   0.969 LogP:   3.406
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.349
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.504
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   20.0
TPSA:   72.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.86 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.113 Fsp3:   0.2
MCE-18:   57.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.859 Fluc inhibitor:   0.783
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.565
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.646
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.268 Promiscuous compounds:   0.122

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.823 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.951 Pgp-substrate:   0.018
PAMPA:   0.025
?
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%):   0.007 30% Bioavailability (F30%):   0.304
50% Bioavailability (F50%):   0.958

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.037 MRP1:   0.846
Plasma Protein Binding (PPB):   98.292% Volume Distribution (VD):   -0.165
Fu: 1.215%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.87
OATP1B3 inhibitor:   0.983 BCRP inhibitor:   0.662
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.255
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.885
?
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):  7.146 Half-life (T1/2):  0.817

ADMET: Toxicity

hERG Blockers:  0.191 hERG Blockers (10um):  0.43
Human Hepatotoxicity (H-HT):  0.938 Drug-induced Liver Injury (DILI):  0.817
AMES Toxicity:  0.628 Rat Oral Acute Toxicity:  0.602
Maximum Recommended Daily Dose:  0.837 Skin Sensitization:  0.916
Carcinogencity:  0.238 Eye Corrosion:  0.008
Eye Irritation:  0.961 Respiratory Toxicity:  0.832
Drug-induced Neurotoxicity:  0.932 Ototoxicity:  0.444
Hematotoxicity:  0.403 Drug-induced Nephrotoxicity:  0.844
Genotoxicity:  0.955 RPMI-8226 Immunitoxicity:  0.192
A549 Cytotoxicity:  0.605 Hek293 Cytotoxicity:  0.397
BCF:   1.374
?
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:   4.121
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.458
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.029
?
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
NPO17729 Tephrosia toxicaria Species Geometridae Eukaryota n.a. stem n.a. PMID[14510590]
NPO17729 Tephrosia toxicaria Species Geometridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17729 Tephrosia toxicaria Species Geometridae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17729 Tephrosia toxicaria Species Geometridae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17729 Tephrosia toxicaria Species Geometridae 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
NPT440 Individual protein Quinone oxidoreductase Mus musculus CD = 10.7 uM PMID[14510590]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ratio > 1.4 n.a. PMID[14510590]
NPT2 Others Unspecified n.a. Inhibition = 0.0 % PMID[14510590]

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 NPC175504 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
0.7167 Intermediate Similarity NPC176229
0.6786 Remote Similarity NPC194432
0.6324 Remote Similarity NPC486093
0.629 Remote Similarity NPC109183
0.6034 Remote Similarity NPC177354
0.6 Remote Similarity NPC316816
0.5846 Remote Similarity NPC470133
0.5763 Remote Similarity NPC150648
0.5763 Remote Similarity NPC37392
0.5714 Remote Similarity NPC147145
0.569 Remote Similarity NPC213322
0.5667 Remote Similarity NPC482119
0.5667 Remote Similarity NPC482120
0.5667 Remote Similarity NPC215885
0.5606 Remote Similarity NPC220998
0.5593 Remote Similarity NPC482121
0.5593 Remote Similarity NPC270964
0.55 Remote Similarity NPC312391
0.5429 Remote Similarity NPC301276
0.5417 Remote Similarity NPC475052
0.541 Remote Similarity NPC255106
0.541 Remote Similarity NPC235165
0.541 Remote Similarity NPC110038
0.5385 Remote Similarity NPC76372
0.5385 Remote Similarity NPC37496
0.5385 Remote Similarity NPC11566
0.5333 Remote Similarity NPC243083
0.5333 Remote Similarity NPC13768
0.5333 Remote Similarity NPC287246
0.5333 Remote Similarity NPC204515
0.5303 Remote Similarity NPC1089
0.5303 Remote Similarity NPC608647
0.5254 Remote Similarity NPC265871
0.5254 Remote Similarity NPC205093
0.5238 Remote Similarity NPC2416
0.5224 Remote Similarity NPC250214
0.5224 Remote Similarity NPC3642
0.5082 Remote Similarity NPC248372
0.5082 Remote Similarity NPC482487
0.5079 Remote Similarity NPC476153
0.5077 Remote Similarity NPC472409
0.5075 Remote Similarity NPC39045

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC175504 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
0.5333 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