Natural Product: NPC474340

Natural Product IDNPC474340
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Methylafromosin
IUPAC Name 6-methoxy-3-(4-methoxyphenyl)-7-methylchromen-4-one
Synonyms 7-O-Methylafromosin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465447
PubChem CID 44567059
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0002687] 4'-O-methylisoflavones

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 JMBQERKOHQZKCY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O4/c1-11-8-17-14(9-16(11)21-3)18(19)15(10-22-17)12-4-6-13(20-2)7-5-12/h4-10H,1-3H3
SMILES COc1ccc(cc1)c1coc2c(c1=O)cc(c(c2)C)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   296.1 Volume:   308.284
?
Van der Waals volume.
Dense:   0.96 LogP:   3.401
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.245
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.817
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.983 Fsp3:   0.167
MCE-18:   17.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.616 Fluc inhibitor:   0.99
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.897
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.67
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.429 Promiscuous compounds:   0.355

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.572 MDCK Permeability:   -4.549
Pgp-inhibitor:   0.825 Pgp-substrate:   0.16
PAMPA:   0.067
?
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):   0.155
20% Bioavailability (F20%):   0.192 30% Bioavailability (F30%):   0.192
50% Bioavailability (F50%):   0.485

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.028 MRP1:   0.874
Plasma Protein Binding (PPB):   93.861% Volume Distribution (VD):   0.012
Fu: 6.521%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.97 BCRP inhibitor:   0.428
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.028 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   0.96 CYP2C9-substrate:   0.557
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.06
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.933
CYP2B6-substrate:   0.319 CYP2C8-inhibitor:   1.0
HLM stability:   0.071
?
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):  7.694 Half-life (T1/2):  0.463

ADMET: Toxicity

hERG Blockers:  0.288 hERG Blockers (10um):  0.554
Human Hepatotoxicity (H-HT):  0.559 Drug-induced Liver Injury (DILI):  0.864
AMES Toxicity:  0.647 Rat Oral Acute Toxicity:  0.461
Maximum Recommended Daily Dose:  0.653 Skin Sensitization:  0.203
Carcinogencity:  0.845 Eye Corrosion:  0.137
Eye Irritation:  0.948 Respiratory Toxicity:  0.761
Drug-induced Neurotoxicity:  0.729 Ototoxicity:  0.285
Hematotoxicity:  0.419 Drug-induced Nephrotoxicity:  0.568
Genotoxicity:  0.487 RPMI-8226 Immunitoxicity:  0.11
A549 Cytotoxicity:  0.129 Hek293 Cytotoxicity:  0.317
BCF:   1.612
?
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:   4.215
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.225
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.799
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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
NPO20912 Wisteria brachybotrys Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[2853205]
NPO20912 Wisteria brachybotrys Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20912 Wisteria brachybotrys Species Fabaceae 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
NPT165 Cell line HeLa Homo sapiens Inhibition = 22.7 % PMID[19035792]
NPT80 Cell line Raji Homo sapiens Activity = 100.0 % PMID[26213786]
NPT80 Cell line Raji Homo sapiens Activity > 80.0 % PMID[9358635]
NPT80 Cell line Raji Homo sapiens Activity = 0.0 % PMID[24582402]
NPT2 Others Unspecified n.a. Activity = 1.0 % PMID[25946116]
NPT2 Others Unspecified n.a. Activity = 100.0 % PMID[15056007]
NPT2 Others Unspecified n.a. Activity = 95.0 % PMID[15056007]
NPT2 Others Unspecified n.a. Activity = 66.8 % PMID[24084296]
NPT2 Others Unspecified n.a. Activity = 0.0 % PMID[24164206]

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 NPC474340 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
0.717 Intermediate Similarity NPC474264
0.6923 Remote Similarity NPC120924
0.6604 Remote Similarity NPC182428
0.6316 Remote Similarity NPC186507
0.6316 Remote Similarity NPC121522
0.614 Remote Similarity NPC603503
0.6034 Remote Similarity NPC136095
0.6032 Remote Similarity NPC488135
0.5893 Remote Similarity NPC223354
0.5862 Remote Similarity NPC10467
0.5763 Remote Similarity NPC209560
0.5763 Remote Similarity NPC490700
0.5614 Remote Similarity NPC195919
0.5593 Remote Similarity NPC116632
0.5556 Remote Similarity NPC254741
0.5484 Remote Similarity NPC220050
0.5469 Remote Similarity NPC606446
0.5469 Remote Similarity NPC607923
0.5424 Remote Similarity NPC185607
0.5333 Remote Similarity NPC35763
0.5333 Remote Similarity NPC333691
0.5312 Remote Similarity NPC478987
0.5246 Remote Similarity NPC181124
0.5246 Remote Similarity NPC69430
0.5246 Remote Similarity NPC124714
0.5246 Remote Similarity NPC294409
0.5246 Remote Similarity NPC490701
0.5246 Remote Similarity NPC610981
0.5167 Remote Similarity NPC605229
0.5161 Remote Similarity NPC181209
0.5161 Remote Similarity NPC148497
0.5139 Remote Similarity NPC135345

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474340 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
NPD

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