Natural Product: NPC469404

Natural Product IDNPC469404
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,4'-Dihydroxy-7-Methoxy-3'-(3-Methyl-2-Hydroxybuten-3-Yl)Isoflavone
IUPAC Name 5-hydroxy-3-[4-hydroxy-3-(2-hydroxy-3-methylbut-2-enyl)phenyl]-7-methoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1077870
PubChem CID 46883038
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002602] 7-O-methylated isoflavonoids
            • [CHEMONTID:0002689] 7-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 XHXNNGVWJWSNFK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O6/c1-11(2)17(23)7-13-6-12(4-5-16(13)22)15-10-27-19-9-14(26-3)8-18(24)20(19)21(15)25/h4-6,8-10,22-24H,7H2,1-3H3
SMILES COc1cc(O)c2c(c1)occ(c2=O)c1ccc(c(c1)CC(=C(C)C)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.13 Volume:   375.116
?
Van der Waals volume.
Dense:   0.981 LogP:   2.984
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.689
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.192
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.595 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.828 Fsp3:   0.19
MCE-18:   20.0
?
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:   0.507 Fluc inhibitor:   0.497
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.955
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.546
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.15 Promiscuous compounds:   0.089

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.023 MDCK Permeability:   -4.801
Pgp-inhibitor:   0.056 Pgp-substrate:   0.086
PAMPA:   0.66
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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):   0.19
20% Bioavailability (F20%):   0.551 30% Bioavailability (F30%):   0.863
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.828
Plasma Protein Binding (PPB):   96.361% Volume Distribution (VD):   -0.38
Fu: 3.121%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.684
BSEP inhibitor:   0.661

ADMET: Metabolism

CYP1A2-inhibitor:   0.899 CYP1A2-substrate:   0.427
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.923 CYP2C9-substrate:   0.087
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.505
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.068
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.442
HLM stability:   0.392
?
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):  6.663 Half-life (T1/2):  0.889

ADMET: Toxicity

hERG Blockers:  0.055 hERG Blockers (10um):  0.043
Human Hepatotoxicity (H-HT):  0.622 Drug-induced Liver Injury (DILI):  0.998
AMES Toxicity:  0.338 Rat Oral Acute Toxicity:  0.797
Maximum Recommended Daily Dose:  0.339 Skin Sensitization:  0.337
Carcinogencity:  0.422 Eye Corrosion:  0.002
Eye Irritation:  0.901 Respiratory Toxicity:  0.826
Drug-induced Neurotoxicity:  0.035 Ototoxicity:  0.663
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.802
Genotoxicity:  0.973 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.018 Hek293 Cytotoxicity:  0.045
BCF:   1.285
?
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:   4.073
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.109
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.611
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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
NPO12590 Erythrina poeppigiana Species Fabaceae Eukaryota n.a. root n.a. PMID[12803562]
NPO12590 Erythrina poeppigiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19705860]
NPO12590 Erythrina poeppigiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12590 Erythrina poeppigiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12590 Erythrina poeppigiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12590 Erythrina poeppigiana 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
NPT108 Individual protein Estrogen receptor alpha Homo sapiens RBA = 0.14 % PMID[19705860]
NPT248 Individual protein Estrogen receptor beta Homo sapiens RBA = 0.06 % PMID[19705860]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ratio IC50 = 2.3 n.a. PMID[18280170]

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 NPC469404 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
0.6615 Remote Similarity NPC303644
0.6232 Remote Similarity NPC114192
0.6212 Remote Similarity NPC116632
0.5811 Remote Similarity NPC249824
0.5789 Remote Similarity NPC253822
0.5634 Remote Similarity NPC90665
0.56 Remote Similarity NPC133400
0.5526 Remote Similarity NPC475705
0.5467 Remote Similarity NPC213659
0.5467 Remote Similarity NPC326109
0.5443 Remote Similarity NPC469405
0.5385 Remote Similarity NPC488570
0.5333 Remote Similarity NPC203636
0.5325 Remote Similarity NPC474993
0.5316 Remote Similarity NPC488567
0.5195 Remote Similarity NPC219917
0.5195 Remote Similarity NPC48624
0.506 Remote Similarity NPC348541

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC469404 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