Natural Product: NPC264289

Natural Product IDNPC264289
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7,3'-Dihydroxy-8,4'-Dimethoxyisoflavone
IUPAC Name 7-hydroxy-3-(3-hydroxy-4-methoxyphenyl)-8-methoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465572
PubChem CID 44257262
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:0003651] 3'-hydroxy,4'-methoxyisoflavonoids

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 YYWSNCLFZSMGCM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O6/c1-21-14-6-3-9(7-13(14)19)11-8-23-16-10(15(11)20)4-5-12(18)17(16)22-2/h3-8,18-19H,1-2H3
SMILES COc1ccc(cc1O)c1coc2c(c1=O)ccc(c2OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   308.569
?
Van der Waals volume.
Dense:   1.018 LogP:   1.612
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.859
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.526
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.375 Fsp3:   0.118
MCE-18:   18.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.291 Fluc inhibitor:   0.96
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.973
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.615
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.439 Promiscuous compounds:   0.706

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.058 MDCK Permeability:   -4.752
Pgp-inhibitor:   0.082 Pgp-substrate:   0.235
PAMPA:   0.366
?
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):   0.149
20% Bioavailability (F20%):   0.529 30% Bioavailability (F30%):   0.698
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.029 MRP1:   0.743
Plasma Protein Binding (PPB):   89.974% Volume Distribution (VD):   -0.523
Fu: 9.895%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.942
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.888
BSEP inhibitor:   0.5

ADMET: Metabolism

CYP1A2-inhibitor:   0.658 CYP1A2-substrate:   0.831
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.239
CYP2C9-inhibitor:   0.884 CYP2C9-substrate:   0.077
CYP2D6-inhibitor:   0.6 CYP2D6-substrate:   0.082
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.438
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   0.995
HLM stability:   0.517
?
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):  3.224 Half-life (T1/2):  1.472

ADMET: Toxicity

hERG Blockers:  0.135 hERG Blockers (10um):  0.548
Human Hepatotoxicity (H-HT):  0.492 Drug-induced Liver Injury (DILI):  0.663
AMES Toxicity:  0.628 Rat Oral Acute Toxicity:  0.528
Maximum Recommended Daily Dose:  0.618 Skin Sensitization:  0.428
Carcinogencity:  0.717 Eye Corrosion:  0.044
Eye Irritation:  0.96 Respiratory Toxicity:  0.787
Drug-induced Neurotoxicity:  0.31 Ototoxicity:  0.312
Hematotoxicity:  0.267 Drug-induced Nephrotoxicity:  0.305
Genotoxicity:  0.471 RPMI-8226 Immunitoxicity:  0.156
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.446
BCF:   0.925
?
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:   3.574
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.328
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.893
?
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
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota seeds n.a. n.a. PMID[12762787]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12762809]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5140 Dipteryx odorata 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
NPT440 Individual protein Quinone oxidoreductase Mus musculus CD > 10.0 ug ml-1 PMID[14510607]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT848 Cell line N9 Homo sapiens IC50 = 67860.0 nM PMID[28073678]

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 NPC264289 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
0.8113 Intermediate Similarity NPC69430
0.7368 Intermediate Similarity NPC80710
0.7193 Intermediate Similarity NPC139293
0.6724 Remote Similarity NPC181209
0.6308 Remote Similarity NPC611071
0.6167 Remote Similarity NPC209487
0.5968 Remote Similarity NPC194653
0.5738 Remote Similarity NPC209560
0.5738 Remote Similarity NPC490700
0.5738 Remote Similarity NPC610981
0.5556 Remote Similarity NPC12377
0.5484 Remote Similarity NPC203747
0.5484 Remote Similarity NPC121522
0.5469 Remote Similarity NPC139364
0.5395 Remote Similarity NPC488565
0.5385 Remote Similarity NPC200060
0.5323 Remote Similarity NPC131266
0.5323 Remote Similarity NPC333691
0.5323 Remote Similarity NPC603503
0.5238 Remote Similarity NPC100971
0.5238 Remote Similarity NPC609386
0.5231 Remote Similarity NPC195763
0.519 Remote Similarity NPC243877
0.5079 Remote Similarity NPC10467

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC264289 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