Natural Product: NPC259411

Natural Product IDNPC259411
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ATGKLATVDOAAOB-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44260028
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 ATGKLATVDOAAOB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H14O9/c1-7(19)26-17-12(25-2)6-11(22)13-14(23)15(24)16(27-18(13)17)8-3-4-9(20)10(21)5-8/h3-6,20-22,24H,1-2H3
SMILES CC(=O)Oc1c(cc(c2c(=O)c(c(c3ccc(c(c3)O)O)oc12)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.06 Volume:   349.599
?
Van der Waals volume.
Dense:   1.07 LogP:   1.398
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.627
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.769
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   146.66
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.308 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.698 Fsp3:   0.111
MCE-18:   21.0
?
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:   1
Colloidal aggregators:   0.607 Fluc inhibitor:   0.235
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.967
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.422
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.363 Promiscuous compounds:   0.678

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.373 MDCK Permeability:   -4.773
Pgp-inhibitor:   0.165 Pgp-substrate:   0.02
PAMPA:   0.254
?
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):   0.246
20% Bioavailability (F20%):   0.833 30% Bioavailability (F30%):   0.991
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.825
Plasma Protein Binding (PPB):   94.998% Volume Distribution (VD):   -0.756
Fu: 3.492%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.882
BSEP inhibitor:   0.372

ADMET: Metabolism

CYP1A2-inhibitor:   0.016 CYP1A2-substrate:   0.037
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.375
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.042 CYP2D6-substrate:   0.275
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.879
HLM stability:   0.94
?
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):  8.814 Half-life (T1/2):  1.407

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.356
Human Hepatotoxicity (H-HT):  0.363 Drug-induced Liver Injury (DILI):  0.931
AMES Toxicity:  0.561 Rat Oral Acute Toxicity:  0.612
Maximum Recommended Daily Dose:  0.466 Skin Sensitization:  0.955
Carcinogencity:  0.33 Eye Corrosion:  0.253
Eye Irritation:  0.978 Respiratory Toxicity:  0.465
Drug-induced Neurotoxicity:  0.015 Ototoxicity:  0.222
Hematotoxicity:  0.186 Drug-induced Nephrotoxicity:  0.019
Genotoxicity:  0.858 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.84 Hek293 Cytotoxicity:  0.264
BCF:   0.816
?
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:   3.531
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.392
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.972
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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
NPO17083 Atraphaxis frutescens Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[28006914]
NPO17083 Atraphaxis frutescens Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17083 Atraphaxis frutescens Species Polygonaceae 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
NPT35 Others n.a. n.a. IC50 = 11200.0 nM PMID[28006914]
NPT2 Others Unspecified n.a. IC50 > 300000.0 nM PMID[28006914]
NPT2 Others Unspecified n.a. IC50 > 5000000.0 nM PMID[28006914]

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 NPC259411 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
0.8596 High Similarity NPC480464
0.6949 Remote Similarity NPC86485
0.6923 Remote Similarity NPC606048
0.678 Remote Similarity NPC301123
0.623 Remote Similarity NPC87125
0.6129 Remote Similarity NPC32420
0.6129 Remote Similarity NPC607913
0.5625 Remote Similarity NPC265115
0.5556 Remote Similarity NPC98661
0.5469 Remote Similarity NPC270465
0.5231 Remote Similarity NPC201451
0.5231 Remote Similarity NPC143799
0.5231 Remote Similarity NPC605144
0.5231 Remote Similarity NPC605755
0.5224 Remote Similarity NPC189179
0.5224 Remote Similarity NPC224137
0.5224 Remote Similarity NPC610401
0.5152 Remote Similarity NPC480465
0.5079 Remote Similarity NPC179271
0.5075 Remote Similarity NPC200740
0.5075 Remote Similarity NPC178854
0.5075 Remote Similarity NPC166753

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC259411 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