Natural Product: NPC258435

Natural Product IDNPC258435
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LHUSIUJRMSQNJO-AWEZNQCLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-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 LHUSIUJRMSQNJO-AWEZNQCLSA-N
Standard InCHI InChI=1S/C16H14O6/c1-21-16-5-9-11(18)6-14(22-15(9)7-13(16)20)8-2-3-10(17)12(19)4-8/h2-5,7,14,17,19-20H,6H2,1H3/t14-/m0/s1
SMILES COc1cc2C(=O)C[C@@H](c3ccc(c(c3)O)O)Oc2cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.08 Volume:   293.909
?
Van der Waals volume.
Dense:   1.028 LogP:   2.106
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.327
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.178
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.902 Fsp3:   0.188
MCE-18:   57.789
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.583 Fluc inhibitor:   0.62
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.84
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.398
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.381 Promiscuous compounds:   0.142

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.046 MDCK Permeability:   -4.773
Pgp-inhibitor:   0.009 Pgp-substrate:   0.009
PAMPA:   0.093
?
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):   0.005
20% Bioavailability (F20%):   0.406 30% Bioavailability (F30%):   0.531
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.815
Plasma Protein Binding (PPB):   93.057% Volume Distribution (VD):   -0.439
Fu: 7.897%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.9
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.521
BSEP inhibitor:   0.205

ADMET: Metabolism

CYP1A2-inhibitor:   0.028 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.104
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.815
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.887
?
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):  8.834 Half-life (T1/2):  2.195

ADMET: Toxicity

hERG Blockers:  0.166 hERG Blockers (10um):  0.594
Human Hepatotoxicity (H-HT):  0.751 Drug-induced Liver Injury (DILI):  0.818
AMES Toxicity:  0.722 Rat Oral Acute Toxicity:  0.681
Maximum Recommended Daily Dose:  0.763 Skin Sensitization:  0.951
Carcinogencity:  0.424 Eye Corrosion:  0.085
Eye Irritation:  0.989 Respiratory Toxicity:  0.855
Drug-induced Neurotoxicity:  0.541 Ototoxicity:  0.595
Hematotoxicity:  0.161 Drug-induced Nephrotoxicity:  0.476
Genotoxicity:  0.969 RPMI-8226 Immunitoxicity:  0.058
A549 Cytotoxicity:  0.897 Hek293 Cytotoxicity:  0.446
BCF:   0.913
?
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:   3.448
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.378
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.943
?
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
NPO28952 Sapium haematospermum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[15104489]
NPO26559 Glycine soja Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21545185]
NPO26531 Aeschrion excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO28952 Sapium haematospermum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8842 Neurymenia fraxinifolia Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10917 Junceella gemmacea Species Ellisellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26559 Glycine soja Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26722 Dorstenia dinklagei Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26881 Croton zehntneri Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8308 Bryocaulon pseudosatoanum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26403 Brachymeris montana n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO26881 Croton zehntneri Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10917 Junceella gemmacea Species Ellisellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26403 Brachymeris montana n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26531 Aeschrion excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO8308 Bryocaulon pseudosatoanum Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26722 Dorstenia dinklagei Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26559 Glycine soja Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28952 Sapium haematospermum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8842 Neurymenia fraxinifolia Species Rhodomelaceae 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 NPC258435 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
0.8 Intermediate Similarity NPC486095
0.7451 Intermediate Similarity NPC99597
0.6923 Remote Similarity NPC1612
0.6923 Remote Similarity NPC183959
0.6792 Remote Similarity NPC610021
0.5965 Remote Similarity NPC474208
0.5926 Remote Similarity NPC103991
0.5789 Remote Similarity NPC321011
0.5789 Remote Similarity NPC294852
0.5789 Remote Similarity NPC210084
0.5789 Remote Similarity NPC188679
0.5763 Remote Similarity NPC474836
0.5556 Remote Similarity NPC329225
0.5556 Remote Similarity NPC147686
0.5424 Remote Similarity NPC599987
0.541 Remote Similarity NPC236637
0.5263 Remote Similarity NPC264083
0.5254 Remote Similarity NPC606248
0.5167 Remote Similarity NPC18727
0.5088 Remote Similarity NPC476480
0.5088 Remote Similarity NPC225153
0.5088 Remote Similarity NPC479876
0.5088 Remote Similarity NPC84585
0.5085 Remote Similarity NPC107551
0.5082 Remote Similarity NPC302950

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC258435 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
0.5556 Remote Similarity NPD1549 Phase 2
0.5082 Remote Similarity NPD1934 Phase 0

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