Natural Product: NPC142495

Natural Product IDNPC142495
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GAZAWYKMEQJTCX-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 70698170
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 GAZAWYKMEQJTCX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O7/c1-22-9-4-12(20)18-13(21)8-14(25-17(18)5-9)10-6-15(23-2)16(24-3)7-11(10)19/h4-8,19-20H,1-3H3
SMILES COc1cc(c2c(=O)cc(c3cc(c(cc3O)OC)OC)oc2c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.09 Volume:   334.655
?
Van der Waals volume.
Dense:   1.028 LogP:   2.504
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.438
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.417
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   98.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.751 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.385 Fsp3:   0.167
MCE-18:   19.0
?
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:   0.329 Fluc inhibitor:   0.413
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.85
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.707
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.393 Promiscuous compounds:   0.712

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.124 MDCK Permeability:   -4.758
Pgp-inhibitor:   0.901 Pgp-substrate:   0.196
PAMPA:   0.013
?
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):   0.088
20% Bioavailability (F20%):   0.046 30% Bioavailability (F30%):   0.226
50% Bioavailability (F50%):   0.935

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.733
Plasma Protein Binding (PPB):   93.123% Volume Distribution (VD):   -0.032
Fu: 5.419%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.997
BSEP inhibitor:   0.983

ADMET: Metabolism

CYP1A2-inhibitor:   0.85 CYP1A2-substrate:   0.728
CYP2C19-inhibitor:   0.01 CYP2C19-substrate:   0.011
CYP2C9-inhibitor:   0.989 CYP2C9-substrate:   0.364
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.987
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.014
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.989
HLM stability:   0.267
?
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):  5.624 Half-life (T1/2):  1.502

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.495
Human Hepatotoxicity (H-HT):  0.439 Drug-induced Liver Injury (DILI):  0.819
AMES Toxicity:  0.619 Rat Oral Acute Toxicity:  0.454
Maximum Recommended Daily Dose:  0.632 Skin Sensitization:  0.433
Carcinogencity:  0.761 Eye Corrosion:  0.329
Eye Irritation:  0.986 Respiratory Toxicity:  0.857
Drug-induced Neurotoxicity:  0.126 Ototoxicity:  0.133
Hematotoxicity:  0.241 Drug-induced Nephrotoxicity:  0.146
Genotoxicity:  0.564 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.249 Hek293 Cytotoxicity:  0.501
BCF:   0.935
?
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:   3.691
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.306
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.643
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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
NPO17263 Mimosa diplotricha Species Fabaceae Eukaryota n.a. aerial part n.a. PMID[21875046]
NPO17263 Mimosa diplotricha Species Fabaceae Eukaryota whole plant Taitung County, Taiwan 2009-MAY PMID[21875046]
NPO17263 Mimosa diplotricha Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[27715048]
NPO17263 Mimosa diplotricha Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17263 Mimosa diplotricha 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC142495 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
0.7143 Intermediate Similarity NPC246204
0.7143 Intermediate Similarity NPC328119
0.7091 Intermediate Similarity NPC33265
0.7091 Intermediate Similarity NPC48479
0.7018 Intermediate Similarity NPC308451
0.7018 Intermediate Similarity NPC124784
0.7018 Intermediate Similarity NPC195202
0.6897 Remote Similarity NPC137062
0.6786 Remote Similarity NPC234133
0.6724 Remote Similarity NPC177298
0.6667 Remote Similarity NPC108406
0.6607 Remote Similarity NPC127447
0.6607 Remote Similarity NPC29353
0.6441 Remote Similarity NPC223579
0.5738 Remote Similarity NPC200388
0.5645 Remote Similarity NPC55619
0.5571 Remote Similarity NPC603508
0.5493 Remote Similarity NPC158027
0.5493 Remote Similarity NPC600396
0.5484 Remote Similarity NPC166753
0.5484 Remote Similarity NPC604677
0.5479 Remote Similarity NPC18699
0.5467 Remote Similarity NPC55443
0.5417 Remote Similarity NPC194593
0.541 Remote Similarity NPC76376
0.5397 Remote Similarity NPC58382
0.5397 Remote Similarity NPC236769
0.5342 Remote Similarity NPC121649
0.5312 Remote Similarity NPC252933
0.5312 Remote Similarity NPC78326
0.527 Remote Similarity NPC205026
0.5211 Remote Similarity NPC248739
0.5205 Remote Similarity NPC159707
0.5205 Remote Similarity NPC14606
0.52 Remote Similarity NPC265624
0.5161 Remote Similarity NPC87125
0.5161 Remote Similarity NPC143799
0.5161 Remote Similarity NPC62536
0.5161 Remote Similarity NPC146679
0.5161 Remote Similarity NPC188871
0.5161 Remote Similarity NPC120464
0.5161 Remote Similarity NPC483773
0.5161 Remote Similarity NPC276409
0.5156 Remote Similarity NPC283600
0.5156 Remote Similarity NPC12200
0.5156 Remote Similarity NPC206604
0.5128 Remote Similarity NPC607707
0.5082 Remote Similarity NPC75279
0.5079 Remote Similarity NPC100916
0.5079 Remote Similarity NPC600900
0.5077 Remote Similarity NPC183950
0.5077 Remote Similarity NPC47781

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC142495 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