Natural Product: NPC490700

Natural Product IDNPC490700
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4Í´-o-methyl-daidzein
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 HKQYGTCOTHHOMP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O4/c1-19-12-5-2-10(3-6-12)14-9-20-15-8-11(17)4-7-13(15)16(14)18/h2-9,17H,1H3
SMILES COC1=CC=C(C2=COC3=CC(O)=CC=C3C2=O)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   268.07 Volume:   273.692
?
Van der Waals volume.
Dense:   0.979 LogP:   2.484
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.78
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.356
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.775 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.952 Fsp3:   0.062
MCE-18:   16.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.457 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.959
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.723
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.798 Promiscuous compounds:   0.734

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.637 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.307 Pgp-substrate:   0.301
PAMPA:   0.201
?
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):   0.18
20% Bioavailability (F20%):   0.653 30% Bioavailability (F30%):   0.825
50% Bioavailability (F50%):   0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.288
Plasma Protein Binding (PPB):   93.82% Volume Distribution (VD):   -0.055
Fu: 6.952%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.745
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.936
BSEP inhibitor:   0.867

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.995
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.455
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.949 CYP2C8-inhibitor:   1.0
HLM stability:   0.032
?
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):  6.504 Half-life (T1/2):  0.805

ADMET: Toxicity

hERG Blockers:  0.269 hERG Blockers (10um):  0.576
Human Hepatotoxicity (H-HT):  0.478 Drug-induced Liver Injury (DILI):  0.778
AMES Toxicity:  0.642 Rat Oral Acute Toxicity:  0.519
Maximum Recommended Daily Dose:  0.734 Skin Sensitization:  0.243
Carcinogencity:  0.805 Eye Corrosion:  0.183
Eye Irritation:  0.983 Respiratory Toxicity:  0.791
Drug-induced Neurotoxicity:  0.554 Ototoxicity:  0.221
Hematotoxicity:  0.204 Drug-induced Nephrotoxicity:  0.271
Genotoxicity:  0.786 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.17 Hek293 Cytotoxicity:  0.537
BCF:   1.311
?
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:   4.008
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.838
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.446
?
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
NPO41785 Shimwellia blattae (p424IbPSO, pIZpntAB) [AdhA; pntAB] Strain n.a. n.a. n.a. n.a. n.a. PMID[33407735]
NPO19632 Terminalia ivorensis Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[36964494]
NPO47851 Escallonia pulverulenta Species Escalloniaceae Eukaryota n.a. n.a. n.a. PMID[39065498]
NPO19632 Terminalia ivorensis Species Combretaceae 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
NPO19632 Terminalia ivorensis Cold water extraction n.a. 0 n.a. n.a. ng/mg PMID[36964494]
NPO19632 Terminalia ivorensis Cold water extraction n.a. 3.2±0.8 n.a. n.a. % PMID[36964494]
NPO19632 Terminalia ivorensis Hot water extraction n.a. 0.01 n.a. n.a. % PMID[36964494]
NPO19632 Terminalia ivorensis Hot water extraction n.a. 3.1±0.7 n.a. n.a. ng/mg PMID[36964494]
NPO19632 Terminalia ivorensis Petroleum ether extract n.a. 3.7±0.9 n.a. n.a. ng/mg PMID[36964494]
NPO19632 Terminalia ivorensis Chloroform extract n.a. 4.4±1.1 n.a. n.a. ng/mg PMID[36964494]
NPO19632 Terminalia ivorensis Ethyl acetate extract n.a. 3.8±0.9 n.a. n.a. ng/mg PMID[36964494]
NPO19632 Terminalia ivorensis Ethanol extract n.a. 3.9±0.9 n.a. n.a. ng/mg PMID[36964494]
NPO47851 Escallonia pulverulenta n.a. n.a. 152.14 ± 2.12 n.a. n.a. mg/100g PMID[39065498]
NPO47851 Escallonia pulverulenta n.a. n.a. 144.95 ± 6.84 n.a. n.a. mg/100g PMID[39065498]

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
NPT692 Individual protein Histone deacetylase 6 Homo sapiens IC50 = 287.9 nM HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 101.85 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 62.62 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692 Individual protein Histone deacetylase 6 Homo sapiens IC50 = 590.7 nM HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 99.63 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT29184 Single protein Sortase A Staphylococcus aureus IC50 = 74900.0 nM PMID[34516107]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[33646787]
NPT28438 Unchecked Unchecked n.a. Ki = 640000.0 nM PMID[33646787]
NPT28438 Unchecked Unchecked n.a. Ki = 2900000.0 nM PMID[33646787]
NPT28438 Unchecked Unchecked n.a. Kq = 0.45 10^13L/mol.s PMID[33646787]
NPT28438 Unchecked Unchecked n.a. Kq = 0.66 10^13L/mol.s PMID[33646787]
NPT28438 Unchecked Unchecked n.a. IC50 = 120000.0 nM PMID[33646787]
NPT28438 Unchecked Unchecked n.a. KSV = 1.02 10^4L/mol PMID[33646787]
NPT28438 Unchecked Unchecked n.a. KSV = 0.72 10^4L/mol PMID[33646787]
NPT28438 Unchecked Unchecked n.a. Kq = 0.64 10^13L/mol.s PMID[33646787]
NPT28438 Unchecked Unchecked n.a. KSV = 1.06 10^4L/mol PMID[33646787]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 477500.0 nM PMID[34516107]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 18.8 % PMID[35489224]





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference
Sus scrofa n.a. Ka = 0.16 10^4L/mol PMID[33646787]
Sus scrofa n.a. Ka = 0.22 10^4L/mol PMID[33646787]
Sus scrofa n.a. Ka = 0.27 10^4L/mol PMID[33646787]





 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 NPC490700 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
1.0 High Similarity NPC209560
0.8113 Intermediate Similarity NPC12377
0.7963 Intermediate Similarity NPC80710
0.7736 Intermediate Similarity NPC609386
0.7636 Intermediate Similarity NPC12175
0.75 Intermediate Similarity NPC55162
0.7407 Intermediate Similarity NPC203747
0.74 Intermediate Similarity NPC234560
0.7321 Intermediate Similarity NPC139364
0.7321 Intermediate Similarity NPC191741
0.7222 Intermediate Similarity NPC10467
0.7091 Intermediate Similarity NPC69430
0.7091 Intermediate Similarity NPC121522
0.7069 Intermediate Similarity NPC35544
0.7018 Intermediate Similarity NPC195763
0.6897 Remote Similarity NPC200060
0.6842 Remote Similarity NPC262623
0.6825 Remote Similarity NPC149875
0.6792 Remote Similarity NPC182428
0.6792 Remote Similarity NPC242893
0.6786 Remote Similarity NPC181124
0.6786 Remote Similarity NPC294409
0.6786 Remote Similarity NPC490701
0.6786 Remote Similarity NPC610981
0.6724 Remote Similarity NPC40290
0.6607 Remote Similarity NPC603503
0.6604 Remote Similarity NPC212767
0.6508 Remote Similarity NPC611071
0.6471 Remote Similarity NPC258035
0.6441 Remote Similarity NPC156953
0.6429 Remote Similarity NPC474264
0.6364 Remote Similarity NPC104406
0.6333 Remote Similarity NPC291802
0.6316 Remote Similarity NPC35763
0.6316 Remote Similarity NPC333691
0.6207 Remote Similarity NPC136095
0.6207 Remote Similarity NPC124714
0.6207 Remote Similarity NPC100971
0.6182 Remote Similarity NPC120924
0.614 Remote Similarity NPC487215
0.6119 Remote Similarity NPC285623
0.6071 Remote Similarity NPC235428
0.6034 Remote Similarity NPC116632
0.6034 Remote Similarity NPC266597
0.6032 Remote Similarity NPC215375
0.6029 Remote Similarity NPC223701
0.6029 Remote Similarity NPC472583
0.6029 Remote Similarity NPC7989
0.5942 Remote Similarity NPC605730
0.5938 Remote Similarity NPC607759
0.5862 Remote Similarity NPC605229
0.5833 Remote Similarity NPC181209
0.5821 Remote Similarity NPC266572
0.5763 Remote Similarity NPC7013
0.5763 Remote Similarity NPC281207
0.5763 Remote Similarity NPC474340
0.5738 Remote Similarity NPC264289
0.5714 Remote Similarity NPC254741
0.5692 Remote Similarity NPC215311
0.5667 Remote Similarity NPC186507
0.5652 Remote Similarity NPC108859
0.5593 Remote Similarity NPC185607
0.5517 Remote Similarity NPC223354
0.5507 Remote Similarity NPC104555
0.55 Remote Similarity NPC269451
0.5484 Remote Similarity NPC139293
0.5484 Remote Similarity NPC200316
0.5479 Remote Similarity NPC607477
0.5467 Remote Similarity NPC488566
0.5441 Remote Similarity NPC610903
0.5439 Remote Similarity NPC218490
0.541 Remote Similarity NPC162680
0.541 Remote Similarity NPC303644
0.5397 Remote Similarity NPC100263
0.5397 Remote Similarity NPC194653
0.5373 Remote Similarity NPC40942
0.5312 Remote Similarity NPC134726
0.5303 Remote Similarity NPC260640
0.5303 Remote Similarity NPC161124
0.5211 Remote Similarity NPC609101
0.5195 Remote Similarity NPC607762
0.5161 Remote Similarity NPC216769
0.5156 Remote Similarity NPC279668
0.5156 Remote Similarity NPC278323
0.5156 Remote Similarity NPC602183
0.5152 Remote Similarity NPC13967
0.5147 Remote Similarity NPC193564
0.5147 Remote Similarity NPC133400
0.5143 Remote Similarity NPC476178
0.5079 Remote Similarity NPC471590
0.5079 Remote Similarity NPC209487
0.5077 Remote Similarity NPC254702
0.5077 Remote Similarity NPC109187
0.5077 Remote Similarity NPC603384
0.5068 Remote Similarity NPC45165

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC490700 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