Natural Product: NPC474037

Natural Product IDNPC474037
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Kaempferol Tetraacetate
IUPAC Name [4-(3,5,7-triacetyloxy-4-oxochromen-2-yl)phenyl] acetate
Synonyms Kaempferol Tetraacetate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458917
PubChem CID 14130926
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones

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 UXAYHERJWMTSFV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H18O10/c1-11(24)29-16-7-5-15(6-8-16)22-23(32-14(4)27)21(28)20-18(31-13(3)26)9-17(30-12(2)25)10-19(20)33-22/h5-10H,1-4H3
SMILES CC(=O)Oc1ccc(cc1)c1oc2cc(OC(=O)C)cc(c2c(=O)c1OC(=O)C)OC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   454.09 Volume:   436.96
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Van der Waals volume.
Dense:   1.039 LogP:   1.831
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.092
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.2
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   22.0
TPSA:   135.41
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Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.418 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.621 Fsp3:   0.174
MCE-18:   22.0
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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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.057 Fluc inhibitor:   0.496
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.993
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.665
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.347 Promiscuous compounds:   0.393

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.87 MDCK Permeability:   -4.499
Pgp-inhibitor:   0.989 Pgp-substrate:   0.012
PAMPA:   0.287
?
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):   0.085
20% Bioavailability (F20%):   0.198 30% Bioavailability (F30%):   0.937
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.701
Plasma Protein Binding (PPB):   81.421% Volume Distribution (VD):   -0.3
Fu: 19.3%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.002
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.747 CYP1A2-substrate:   0.314
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.019
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.073
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.999
?
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):  2.451 Half-life (T1/2):  0.495

ADMET: Toxicity

hERG Blockers:  0.002 hERG Blockers (10um):  0.063
Human Hepatotoxicity (H-HT):  0.299 Drug-induced Liver Injury (DILI):  0.994
AMES Toxicity:  0.446 Rat Oral Acute Toxicity:  0.704
Maximum Recommended Daily Dose:  0.22 Skin Sensitization:  0.968
Carcinogencity:  0.127 Eye Corrosion:  0.662
Eye Irritation:  0.893 Respiratory Toxicity:  0.086
Drug-induced Neurotoxicity:  0.086 Ototoxicity:  0.034
Hematotoxicity:  0.565 Drug-induced Nephrotoxicity:  0.008
Genotoxicity:  0.964 RPMI-8226 Immunitoxicity:  0.015
A549 Cytotoxicity:  0.788 Hek293 Cytotoxicity:  0.125
BCF:   0.804
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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:   3.757
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.816
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.527
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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
NPO28094 Consolida oliveriana Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[19489596]
NPO33118 Rhamnus Genus Rhamnaceae Eukaryota n.a. n.a. n.a. PMID[8350094]
NPO28094 Consolida oliveriana Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28094 Consolida oliveriana Species Ranunculaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1597 Cell line J774.2 n.a. IC50 = 15560.0 nM PMID[17970596]
NPT839 Cell line L6 Rattus norvegicus Activity = 99.7 % PMID[23628332]
NPT839 Cell line L6 Rattus norvegicus Activity = 91.3 % PMID[18458131]
NPT319 Cell line B16 Mus musculus IC50 = 40700.0 nM PMID[19581457]
NPT1225 Organism Plasmodium falciparum (isolate FcB1 / Columbia) Plasmodium falciparum FcB1/Columbia GI = 3.6 % PMID[24033101]
NPT2229 Organism Trypanosoma brucei gambiense Trypanosoma brucei gambiense GI = 13.7 % PMID[22377672]
NPT2229 Organism Trypanosoma brucei gambiense Trypanosoma brucei gambiense GI = 0.0 % PMID[20159656]
NPT1596 Organism Leishmania peruviana Leishmania peruviana IC50 = 53320.0 nM PMID[19013063]
NPT1208 Organism Leishmania braziliensis Leishmania braziliensis IC50 = 68560.0 nM PMID[16562830]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity > 100.0 uM PMID[25659770]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 = 48520.0 nM PMID[1965654]
NPT20967 Cell line Platelet n.a. Activity = 17.4 % PMID[8350094]
NPT20967 Cell line Platelet n.a. Activity = 15.9 % PMID[8350094]
NPT20967 Cell line Platelet n.a. Activity = 14.5 % PMID[8350094]

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 NPC474037 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
0.8776 High Similarity NPC605569
0.7925 Intermediate Similarity NPC177839
0.7321 Intermediate Similarity NPC472535
0.7143 Intermediate Similarity NPC474170
0.7143 Intermediate Similarity NPC474388
0.6863 Remote Similarity NPC72452
0.6316 Remote Similarity NPC153758
0.6286 Remote Similarity NPC117478
0.6197 Remote Similarity NPC481404
0.5972 Remote Similarity NPC321478
0.5926 Remote Similarity NPC61546
0.5789 Remote Similarity NPC90582
0.5789 Remote Similarity NPC310259
0.5714 Remote Similarity NPC473516
0.55 Remote Similarity NPC605582
0.5323 Remote Similarity NPC608137
0.5263 Remote Similarity NPC69752
0.5263 Remote Similarity NPC602291
0.5256 Remote Similarity NPC475214
0.5246 Remote Similarity NPC470216

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474037 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