Natural Product: NPC136095

Natural Product IDNPC136095
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Acetylformononetin
IUPAC Name [3-(4-methoxyphenyl)-4-oxochromen-7-yl] acetate
Synonyms 7-O-Acetylformononetin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL463063
PubChem CID 908827
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 GGGJVAAAUYBGSQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H14O5/c1-11(19)23-14-7-8-15-17(9-14)22-10-16(18(15)20)12-3-5-13(21-2)6-4-12/h3-10H,1-2H3
SMILES CC(=O)Oc1ccc2c(c1)occ(c1ccc(cc1)OC)c2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.08 Volume:   314.438
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Van der Waals volume.
Dense:   0.986 LogP:   2.411
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.607
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.893
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   65.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.548 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.025 Fsp3:   0.111
MCE-18:   17.0
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.347 Fluc inhibitor:   0.988
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.951
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.639
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.545 Promiscuous compounds:   0.388

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.696 MDCK Permeability:   -4.499
Pgp-inhibitor:   0.443 Pgp-substrate:   0.089
PAMPA:   0.519
?
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):   0.477
20% Bioavailability (F20%):   0.322 30% Bioavailability (F30%):   0.49
50% Bioavailability (F50%):   0.879

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.795
Plasma Protein Binding (PPB):   91.521% Volume Distribution (VD):   -0.082
Fu: 10.621%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.938
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.528
BSEP inhibitor:   0.971

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.811
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.541
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.981
CYP2B6-substrate:   0.998 CYP2C8-inhibitor:   1.0
HLM stability:   0.054
?
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):  4.669 Half-life (T1/2):  0.488

ADMET: Toxicity

hERG Blockers:  0.146 hERG Blockers (10um):  0.428
Human Hepatotoxicity (H-HT):  0.437 Drug-induced Liver Injury (DILI):  0.924
AMES Toxicity:  0.602 Rat Oral Acute Toxicity:  0.514
Maximum Recommended Daily Dose:  0.514 Skin Sensitization:  0.333
Carcinogencity:  0.693 Eye Corrosion:  0.179
Eye Irritation:  0.948 Respiratory Toxicity:  0.624
Drug-induced Neurotoxicity:  0.591 Ototoxicity:  0.194
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.283
Genotoxicity:  0.684 RPMI-8226 Immunitoxicity:  0.06
A549 Cytotoxicity:  0.183 Hek293 Cytotoxicity:  0.265
BCF:   1.188
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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:   4.0
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.026
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.713
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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 = 40.2 % PMID[16933872]
NPT80 Cell line Raji Homo sapiens Activity = 100.0 % PMID[25462220]
NPT80 Cell line Raji Homo sapiens Activity > 80.0 % PMID[17848089]
NPT80 Cell line Raji Homo sapiens Activity = 80.0 % PMID[17848089]
NPT2 Others Unspecified n.a. Activity = 0.0 % PMID[19433554]
NPT2 Others Unspecified n.a. Activity = 100.0 % PMID[20439614]
NPT2 Others Unspecified n.a. Activity = 95.2 % PubChem BioAssay data set
NPT2 Others Unspecified n.a. Activity = 15.2 % PubChem BioAssay data set

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 NPC136095 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
0.8542 High Similarity NPC182428
0.7407 Intermediate Similarity NPC186507
0.7368 Intermediate Similarity NPC254741
0.7037 Intermediate Similarity NPC185607
0.6792 Remote Similarity NPC120924
0.6786 Remote Similarity NPC181124
0.6607 Remote Similarity NPC479067
0.6441 Remote Similarity NPC602183
0.6429 Remote Similarity NPC474264
0.6379 Remote Similarity NPC471590
0.6316 Remote Similarity NPC216314
0.6316 Remote Similarity NPC603503
0.6207 Remote Similarity NPC209560
0.6207 Remote Similarity NPC490700
0.619 Remote Similarity NPC185401
0.6087 Remote Similarity NPC478528
0.6071 Remote Similarity NPC223354
0.6034 Remote Similarity NPC474340
0.5942 Remote Similarity NPC45165
0.5938 Remote Similarity NPC488135
0.5932 Remote Similarity NPC121522
0.589 Remote Similarity NPC43761
0.5797 Remote Similarity NPC487214
0.5763 Remote Similarity NPC10467
0.5763 Remote Similarity NPC116632
0.5763 Remote Similarity NPC333691
0.5735 Remote Similarity NPC25547
0.5556 Remote Similarity NPC153008
0.5517 Remote Similarity NPC195919
0.5469 Remote Similarity NPC478987
0.541 Remote Similarity NPC69430
0.541 Remote Similarity NPC124714
0.541 Remote Similarity NPC610981
0.5385 Remote Similarity NPC13967
0.5385 Remote Similarity NPC607923
0.5333 Remote Similarity NPC103001
0.5246 Remote Similarity NPC35763
0.5231 Remote Similarity NPC478213
0.5161 Remote Similarity NPC294409
0.5161 Remote Similarity NPC490701
0.5156 Remote Similarity NPC220050
0.5152 Remote Similarity NPC606446
0.5147 Remote Similarity NPC133400
0.5082 Remote Similarity NPC605229
0.5079 Remote Similarity NPC148497

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC136095 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
0.6607 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