Natural Product: NPC264550

Natural Product IDNPC264550
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2'-Hydroxy-3'-Methoxygenistein
IUPAC Name 3-(2,4-dihydroxy-3-methoxyphenyl)-5,7-dihydroxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1076318
PubChem CID 46879792
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002605] 3'-O-methylated isoflavonoids
            • [CHEMONTID:0002690] 3'-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 SIWJGAYTMXOGHW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O7/c1-22-16-10(18)3-2-8(15(16)21)9-6-23-12-5-7(17)4-11(19)13(12)14(9)20/h2-6,17-19,21H,1H3
SMILES COc1c(O)ccc(c1O)c1coc2c(c1=O)c(O)cc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.06 Volume:   300.063
?
Van der Waals volume.
Dense:   1.053 LogP:   1.512
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.78
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.016
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   120.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.572 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.681 Fsp3:   0.062
MCE-18:   19.0
?
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:   0.702 Fluc inhibitor:   0.606
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.884
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.393
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.568 Promiscuous compounds:   0.871

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.279 MDCK Permeability:   -4.863
Pgp-inhibitor:   0.004 Pgp-substrate:   0.262
PAMPA:   0.815
?
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):   0.018
20% Bioavailability (F20%):   0.338 30% Bioavailability (F30%):   0.831
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.017 MRP1:   0.757
Plasma Protein Binding (PPB):   95.567% Volume Distribution (VD):   -0.652
Fu: 3.957%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.785
OATP1B3 inhibitor:   0.943 BCRP inhibitor:   0.85
BSEP inhibitor:   0.035

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.471
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.234
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.205
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.949
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.048
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.951
?
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):  1.596 Half-life (T1/2):  1.696

ADMET: Toxicity

hERG Blockers:  0.081 hERG Blockers (10um):  0.497
Human Hepatotoxicity (H-HT):  0.42 Drug-induced Liver Injury (DILI):  0.804
AMES Toxicity:  0.624 Rat Oral Acute Toxicity:  0.591
Maximum Recommended Daily Dose:  0.804 Skin Sensitization:  0.589
Carcinogencity:  0.695 Eye Corrosion:  0.04
Eye Irritation:  0.992 Respiratory Toxicity:  0.855
Drug-induced Neurotoxicity:  0.068 Ototoxicity:  0.17
Hematotoxicity:  0.084 Drug-induced Nephrotoxicity:  0.107
Genotoxicity:  0.949 RPMI-8226 Immunitoxicity:  0.095
A549 Cytotoxicity:  0.415 Hek293 Cytotoxicity:  0.637
BCF:   0.978
?
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:   3.602
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.35
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.793
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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
NPO6711 Streptomyces mirabilis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[19818612]
NPO6711 Streptomyces mirabilis Species Streptomycetaceae Bacteria 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
NPT737 Cell line HUVEC Homo sapiens GI50 = 64000.0 nM Open TG-GATES in vivo data: Biochemistry
NPT111 Cell line K562 Homo sapiens GI50 = 48000.0 nM PMID[11429990]
NPT83 Cell line MCF7 Homo sapiens GI50 = 15000.0 nM PMID[9917289]
NPT165 Cell line HeLa Homo sapiens CC50 = 77000.0 nM PMID[11429990]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 32000.0 nM PMID[19818612]

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 NPC264550 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
0.7119 Intermediate Similarity NPC40290
0.7 Intermediate Similarity NPC254702
0.7 Intermediate Similarity NPC483637
0.6833 Remote Similarity NPC279668
0.6786 Remote Similarity NPC87545
0.6721 Remote Similarity NPC45291
0.6667 Remote Similarity NPC309154
0.661 Remote Similarity NPC294409
0.661 Remote Similarity NPC490701
0.6557 Remote Similarity NPC194653
0.65 Remote Similarity NPC19980
0.6441 Remote Similarity NPC78341
0.6393 Remote Similarity NPC200316
0.629 Remote Similarity NPC278323
0.629 Remote Similarity NPC481044
0.623 Remote Similarity NPC239363
0.619 Remote Similarity NPC142876
0.614 Remote Similarity NPC39426
0.5932 Remote Similarity NPC38065
0.5862 Remote Similarity NPC608554
0.5821 Remote Similarity NPC232947
0.5781 Remote Similarity NPC90665
0.5758 Remote Similarity NPC167595
0.569 Remote Similarity NPC193792
0.5652 Remote Similarity NPC233918
0.5645 Remote Similarity NPC269451
0.5606 Remote Similarity NPC104728
0.5571 Remote Similarity NPC479305
0.5571 Remote Similarity NPC128774
0.5479 Remote Similarity NPC474960
0.5455 Remote Similarity NPC476055
0.5429 Remote Similarity NPC268059
0.5417 Remote Similarity NPC231763
0.5417 Remote Similarity NPC482075
0.5397 Remote Similarity NPC131266
0.5385 Remote Similarity NPC121527
0.5352 Remote Similarity NPC280937
0.5312 Remote Similarity NPC245382
0.5217 Remote Similarity NPC608523
0.5205 Remote Similarity NPC303197
0.5156 Remote Similarity NPC35763
0.5143 Remote Similarity NPC213659
0.5143 Remote Similarity NPC85131
0.5143 Remote Similarity NPC326109
0.5077 Remote Similarity NPC303644
0.507 Remote Similarity NPC606200
0.5068 Remote Similarity NPC474052

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC264550 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
0.614 Remote Similarity NPD1510 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