Natural Product: NPC276905

Natural Product IDNPC276905
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7,4'-Tri-O-Methylkaempferol
IUPAC Name 3-hydroxy-5,7-dimethoxy-2-(4-methoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2331821
PubChem CID 624831
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 SGPXJCVFCJANKN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O6/c1-21-11-6-4-10(5-7-11)18-17(20)16(19)15-13(23-3)8-12(22-2)9-14(15)24-18/h4-9,20H,1-3H3
SMILES COc1ccc(cc1)c1c(c(=O)c2c(cc(cc2o1)OC)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.09 Volume:   325.865
?
Van der Waals volume.
Dense:   1.007 LogP:   2.588
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.743
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.09
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   78.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.792 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.146 Fsp3:   0.167
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:   0.321 Fluc inhibitor:   0.932
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.885
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.693
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.342 Promiscuous compounds:   0.677

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.001 MDCK Permeability:   -4.691
Pgp-inhibitor:   0.983 Pgp-substrate:   0.035
PAMPA:   0.024
?
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):   0.682
20% Bioavailability (F20%):   0.05 30% Bioavailability (F30%):   0.282
50% Bioavailability (F50%):   0.846

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.481
Plasma Protein Binding (PPB):   92.294% Volume Distribution (VD):   -0.51
Fu: 5.928%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.986
BSEP inhibitor:   0.984

ADMET: Metabolism

CYP1A2-inhibitor:   0.973 CYP1A2-substrate:   0.508
CYP2C19-inhibitor:   0.09 CYP2C19-substrate:   0.81
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.031
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.882
CYP3A4-inhibitor:   0.011 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   1.0
HLM stability:   0.976
?
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):  6.233 Half-life (T1/2):  0.778

ADMET: Toxicity

hERG Blockers:  0.166 hERG Blockers (10um):  0.482
Human Hepatotoxicity (H-HT):  0.477 Drug-induced Liver Injury (DILI):  0.913
AMES Toxicity:  0.643 Rat Oral Acute Toxicity:  0.45
Maximum Recommended Daily Dose:  0.657 Skin Sensitization:  0.245
Carcinogencity:  0.847 Eye Corrosion:  0.288
Eye Irritation:  0.968 Respiratory Toxicity:  0.74
Drug-induced Neurotoxicity:  0.3 Ototoxicity:  0.164
Hematotoxicity:  0.377 Drug-induced Nephrotoxicity:  0.231
Genotoxicity:  0.592 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.144 Hek293 Cytotoxicity:  0.374
BCF:   1.105
?
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:   3.857
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.611
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.153
?
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
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota leaves, twigs, and fruits Nui Chua National Park (11 43' N; 109 08' E; 730 m alt.), Ninh Thuan Province, Vietnam 2010-Jan PMID[23301897]
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[31621322]
NPO24576 Genista lydia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3711 Acalypha australis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23426 Andromeda polifolia Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24184 Argyrochosma pilifera Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24139 Calamus strictus Species Sparidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24496 Gymnopetalum integrifolium Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13008 Methanobrevibacter arboriphilus Species Methanobacteriaceae Archaea n.a. n.a. n.a. Database[COCONUT]
NPO22683 Pteris bella Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24014 Scapania bolanderi Species Scapaniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23300 Trichilia heudelotii Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25120 Vincetoxicum forrestii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24496 Gymnopetalum integrifolium Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22683 Pteris bella Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24184 Argyrochosma pilifera Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24576 Genista lydia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4720 Aglaia perviridis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24014 Scapania bolanderi Species Scapaniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22683 Pteris bella Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24139 Calamus strictus Species Sparidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24496 Gymnopetalum integrifolium Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3711 Acalypha australis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25120 Vincetoxicum forrestii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13008 Methanobrevibacter arboriphilus Species Methanobacteriaceae Archaea n.a. n.a. n.a. Database[UNPD]
NPO23426 Andromeda polifolia Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23300 Trichilia heudelotii Species Meliaceae 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
NPT1422 Individual protein ATP-binding cassette sub-family G member 2 Homo sapiens IC50 = 12400.0 nM PMID[23851114]
NPT1422 Individual protein ATP-binding cassette sub-family G member 2 Homo sapiens IC50 = 8950.0 nM PMID[23851114]
NPT721 Individual protein Nuclear factor NF-kappa-B p65 subunit Homo sapiens ED50 > 20.0 uM PMID[23301897]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT139 Cell line HT-29 Homo sapiens ED50 > 10.0 uM PMID[23301897]

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 NPC276905 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
0.8269 Intermediate Similarity NPC261548
0.6415 Remote Similarity NPC72452
0.6316 Remote Similarity NPC49824
0.6296 Remote Similarity NPC101294
0.625 Remote Similarity NPC44079
0.614 Remote Similarity NPC241838
0.614 Remote Similarity NPC281207
0.614 Remote Similarity NPC605146
0.5932 Remote Similarity NPC50728
0.5932 Remote Similarity NPC605582
0.5862 Remote Similarity NPC270465
0.5833 Remote Similarity NPC75215
0.5763 Remote Similarity NPC269652
0.569 Remote Similarity NPC90582
0.569 Remote Similarity NPC152042
0.569 Remote Similarity NPC310259
0.5667 Remote Similarity NPC200740
0.5667 Remote Similarity NPC166753
0.5667 Remote Similarity NPC602344
0.5593 Remote Similarity NPC201451
0.5593 Remote Similarity NPC70853
0.5593 Remote Similarity NPC87125
0.5593 Remote Similarity NPC143799
0.55 Remote Similarity NPC86485
0.5484 Remote Similarity NPC608137
0.5333 Remote Similarity NPC605755
0.5323 Remote Similarity NPC179126
0.5294 Remote Similarity NPC280975
0.5263 Remote Similarity NPC61546
0.5246 Remote Similarity NPC605569
0.5238 Remote Similarity NPC604021
0.5233 Remote Similarity NPC244875
0.5172 Remote Similarity NPC278556
0.5172 Remote Similarity NPC602291
0.5167 Remote Similarity NPC262094
0.5167 Remote Similarity NPC29353
0.5085 Remote Similarity NPC29536
0.5085 Remote Similarity NPC223354
0.5082 Remote Similarity NPC22519
0.5079 Remote Similarity NPC93376
0.5077 Remote Similarity NPC607815

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC276905 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