Natural Product: NPC474264

Natural Product IDNPC474264
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Methylformononetin
IUPAC Name 3-(4-methoxyphenyl)-7-methylchromen-4-one
Synonyms 7-O-Methylformononetin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464456
PubChem CID 584452
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 PJZVNCZNTQDLPS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O3/c1-11-3-8-14-16(9-11)20-10-15(17(14)18)12-4-6-13(19-2)7-5-12/h3-10H,1-2H3
SMILES CC1=CC2=C(C=C1)C(=O)C(=CO2)C3=CC=C(C=C3)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   266.09 Volume:   282.198
?
Van der Waals volume.
Dense:   0.943 LogP:   3.495
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.209
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.767
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   39.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.708 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.858 Fsp3:   0.118
MCE-18:   16.0
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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:   0.712 Fluc inhibitor:   0.999
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.911
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.845
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.733 Promiscuous compounds:   0.31

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.575 MDCK Permeability:   -4.534
Pgp-inhibitor:   0.839 Pgp-substrate:   0.161
PAMPA:   0.206
?
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):   0.049
20% Bioavailability (F20%):   0.239 30% Bioavailability (F30%):   0.349
50% Bioavailability (F50%):   0.441

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.101 MRP1:   0.867
Plasma Protein Binding (PPB):   97.038% Volume Distribution (VD):   0.06
Fu: 2.568%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.966
OATP1B3 inhibitor:   0.957 BCRP inhibitor:   0.164
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.986
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.097
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.941 CYP2C8-inhibitor:   1.0
HLM stability:   0.039
?
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):  6.631 Half-life (T1/2):  0.494

ADMET: Toxicity

hERG Blockers:  0.301 hERG Blockers (10um):  0.59
Human Hepatotoxicity (H-HT):  0.512 Drug-induced Liver Injury (DILI):  0.85
AMES Toxicity:  0.631 Rat Oral Acute Toxicity:  0.493
Maximum Recommended Daily Dose:  0.606 Skin Sensitization:  0.202
Carcinogencity:  0.803 Eye Corrosion:  0.218
Eye Irritation:  0.971 Respiratory Toxicity:  0.782
Drug-induced Neurotoxicity:  0.683 Ototoxicity:  0.278
Hematotoxicity:  0.372 Drug-induced Nephrotoxicity:  0.438
Genotoxicity:  0.472 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.141 Hek293 Cytotoxicity:  0.289
BCF:   1.634
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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:   4.19
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.033
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.735
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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 = 34.3 % PMID[19035792]
NPT80 Cell line Raji Homo sapiens Activity = 100.0 % PMID[26213786]
NPT80 Cell line Raji Homo sapiens Activity = 80.0 % DrugMatrix in vivo data: Pathology
NPT2 Others Unspecified n.a. Activity = 0.0 % PMID[25946116]
NPT2 Others Unspecified n.a. Activity = 100.0 % PMID[15056007]
NPT2 Others Unspecified n.a. Activity = 90.2 % PMID[24084296]
NPT2 Others Unspecified n.a. Activity = 30.3 % 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 NPC474264 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 NPC474340
0.7059 Intermediate Similarity NPC182428
0.6429 Remote Similarity NPC136095
0.6429 Remote Similarity NPC209560
0.6429 Remote Similarity NPC490700
0.6415 Remote Similarity NPC120924
0.5965 Remote Similarity NPC10467
0.5965 Remote Similarity NPC603503
0.5902 Remote Similarity NPC254741
0.5862 Remote Similarity NPC186507
0.5862 Remote Similarity NPC121522
0.5789 Remote Similarity NPC185607
0.5714 Remote Similarity NPC223354
0.569 Remote Similarity NPC333691
0.5593 Remote Similarity NPC181124
0.5593 Remote Similarity NPC69430
0.5593 Remote Similarity NPC610981
0.5424 Remote Similarity NPC116632
0.5424 Remote Similarity NPC35763
0.5397 Remote Similarity NPC478987
0.5385 Remote Similarity NPC488135
0.5333 Remote Similarity NPC124714
0.5333 Remote Similarity NPC294409
0.5333 Remote Similarity NPC490701
0.5323 Remote Similarity NPC602183
0.5312 Remote Similarity NPC607923
0.5172 Remote Similarity NPC195919
0.5167 Remote Similarity NPC479067
0.5161 Remote Similarity NPC12377
0.5079 Remote Similarity NPC80710
0.5079 Remote Similarity NPC220050
0.5077 Remote Similarity NPC13967
0.5077 Remote Similarity NPC606446

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474264 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
0.5167 Remote Similarity NPD2796 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