Natural Product: NPC215203

Natural Product IDNPC215203
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4',7''-O-Methylamentoflavone
IUPAC Name 8-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-methoxyphenyl]-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxychromen-4-one
Synonyms 4',7'-O-Methylamentoflavone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL208988
PubChem CID 5494869
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 OVCFMRWVQJAWDY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C32H22O10/c1-39-24-8-5-16(26-12-21(36)30-20(35)10-18(34)11-28(30)41-26)9-19(24)29-27(40-2)14-23(38)31-22(37)13-25(42-32(29)31)15-3-6-17(33)7-4-15/h3-14,33-35,38H,1-2H3
SMILES COc1ccc(cc1c1c(OC)cc(c2c1oc(cc2=O)c1ccc(cc1)O)O)c1cc(=O)c2c(o1)cc(cc2O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   566.12 Volume:   556.408
?
Van der Waals volume.
Dense:   1.017 LogP:   4.413
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.522
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.681
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   36.0
TPSA:   159.8
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   4.0 Rings:   6.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.203 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.001 Fsp3:   0.062
MCE-18:   36.0
?
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:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.993 Fluc inhibitor:   0.281
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.968
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.997
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.337 Promiscuous compounds:   0.879

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.992 MDCK Permeability:   -4.791
Pgp-inhibitor:   0.022 Pgp-substrate:   0.405
PAMPA:   0.108
?
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):   0.001
20% Bioavailability (F20%):   0.29 30% Bioavailability (F30%):   0.807
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.857
Plasma Protein Binding (PPB):   97.053% Volume Distribution (VD):   -0.25
Fu: 2.323%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.979
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.463 CYP1A2-substrate:   0.026
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.626 CYP2C9-substrate:   0.942
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.077
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.689
?
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):  2.66 Half-life (T1/2):  1.656

ADMET: Toxicity

hERG Blockers:  0.102 hERG Blockers (10um):  0.515
Human Hepatotoxicity (H-HT):  0.5 Drug-induced Liver Injury (DILI):  0.987
AMES Toxicity:  0.729 Rat Oral Acute Toxicity:  0.62
Maximum Recommended Daily Dose:  0.984 Skin Sensitization:  0.358
Carcinogencity:  0.886 Eye Corrosion:  0.002
Eye Irritation:  0.991 Respiratory Toxicity:  0.871
Drug-induced Neurotoxicity:  0.011 Ototoxicity:  0.058
Hematotoxicity:  0.037 Drug-induced Nephrotoxicity:  0.014
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.108
A549 Cytotoxicity:  0.614 Hek293 Cytotoxicity:  0.97
BCF:   1.324
?
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:   4.602
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.102
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.829
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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
NPO2284 Cephalotaxus koreana Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[16574412]
NPO2284 Cephalotaxus koreana Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[17994703]
NPO2284 Cephalotaxus koreana Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2284 Cephalotaxus koreana Species Taxaceae 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
NPT740 Individual protein Beta-secretase 1 Homo sapiens IC50 > 10000.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1309 Cell line Osteoblasts n.a. Activity = 113.0 % PMID[24679044]
NPT1309 Cell line Osteoblasts n.a. Activity = 101.1 % PMID[22664131]
NPT1309 Cell line Osteoblasts n.a. Activity = 73.5 % PMID[23002924]
NPT20 Organism Candida albicans Candida albicans IC50 > 50.0 ug.mL-1 PMID[226705]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 56.5 % PMID[26004578]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans IC50 > 50.0 ug.mL-1 Open TG-GATES in vivo data: Hematology
NPT2 Others Unspecified n.a. IC50 = 49.0 ug.mL-1 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 NPC215203 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
0.8955 High Similarity NPC186227
0.8143 Intermediate Similarity NPC159707
0.8 Intermediate Similarity NPC290830
0.8 Intermediate Similarity NPC71061
0.7671 Intermediate Similarity NPC601565
0.726 Intermediate Similarity NPC72425
0.7222 Intermediate Similarity NPC248739
0.7123 Intermediate Similarity NPC150908
0.7105 Intermediate Similarity NPC265624
0.6765 Remote Similarity NPC610914
0.6579 Remote Similarity NPC303485
0.6447 Remote Similarity NPC603508
0.6418 Remote Similarity NPC231772
0.6329 Remote Similarity NPC205026
0.6282 Remote Similarity NPC14606
0.625 Remote Similarity NPC50898
0.6234 Remote Similarity NPC601984
0.6164 Remote Similarity NPC138299
0.6154 Remote Similarity NPC158027
0.6076 Remote Similarity NPC194593
0.6029 Remote Similarity NPC52611
0.6026 Remote Similarity NPC600972
0.5915 Remote Similarity NPC52005
0.5915 Remote Similarity NPC12200
0.5875 Remote Similarity NPC272064
0.5833 Remote Similarity NPC183950
0.5802 Remote Similarity NPC121649
0.5714 Remote Similarity NPC234133
0.557 Remote Similarity NPC259757
0.5529 Remote Similarity NPC55443
0.5526 Remote Similarity NPC111112
0.5513 Remote Similarity NPC34089
0.5513 Remote Similarity NPC183
0.5513 Remote Similarity NPC196179
0.5513 Remote Similarity NPC254351
0.5493 Remote Similarity NPC62536
0.5493 Remote Similarity NPC120464
0.5493 Remote Similarity NPC483773
0.5493 Remote Similarity NPC601901
0.5455 Remote Similarity NPC288840
0.5362 Remote Similarity NPC279121
0.5352 Remote Similarity NPC241498
0.5294 Remote Similarity NPC78540
0.527 Remote Similarity NPC606638
0.5263 Remote Similarity NPC605634
0.5256 Remote Similarity NPC112954
0.5256 Remote Similarity NPC291746
0.5217 Remote Similarity NPC222713
0.5139 Remote Similarity NPC301323
0.5139 Remote Similarity NPC103342
0.5139 Remote Similarity NPC47815
0.5139 Remote Similarity NPC29353
0.5132 Remote Similarity NPC67322
0.5062 Remote Similarity NPC610480

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC215203 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
0.5362 Remote Similarity NPD1511 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