Natural Product: NPC333230

Natural Product IDNPC333230
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NVTJLSRVWFAVPB-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 315709
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 NVTJLSRVWFAVPB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O6/c1-21-14-6-5-11(7-17(14)22-2)15-9-13(20)12-8-18(23-3)19(24-4)10-16(12)25-15/h5-10H,1-4H3
SMILES COc1ccc(cc1OC)c1cc(=O)c2cc(c(cc2o1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.11 Volume:   343.16
?
Van der Waals volume.
Dense:   0.997 LogP:   2.278
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.608
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.668
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   67.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.707 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.021 Fsp3:   0.211
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.134 Fluc inhibitor:   0.737
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.965
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.581
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.395 Promiscuous compounds:   0.795

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.564 MDCK Permeability:   -4.585
Pgp-inhibitor:   0.98 Pgp-substrate:   0.067
PAMPA:   0.008
?
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):   0.234
20% Bioavailability (F20%):   0.124 30% Bioavailability (F30%):   0.067
50% Bioavailability (F50%):   0.851

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.918
Plasma Protein Binding (PPB):   93.049% Volume Distribution (VD):   -0.092
Fu: 6.874%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.726 CYP1A2-substrate:   0.633
CYP2C19-inhibitor:   0.976 CYP2C19-substrate:   0.166
CYP2C9-inhibitor:   0.793 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.777
CYP3A4-inhibitor:   0.997 CYP3A4-substrate:   0.834
CYP2B6-substrate:   0.101 CYP2C8-inhibitor:   0.989
HLM stability:   0.263
?
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):  7.11 Half-life (T1/2):  2.405

ADMET: Toxicity

hERG Blockers:  0.107 hERG Blockers (10um):  0.41
Human Hepatotoxicity (H-HT):  0.43 Drug-induced Liver Injury (DILI):  0.756
AMES Toxicity:  0.563 Rat Oral Acute Toxicity:  0.422
Maximum Recommended Daily Dose:  0.625 Skin Sensitization:  0.289
Carcinogencity:  0.83 Eye Corrosion:  0.661
Eye Irritation:  0.978 Respiratory Toxicity:  0.722
Drug-induced Neurotoxicity:  0.417 Ototoxicity:  0.121
Hematotoxicity:  0.439 Drug-induced Nephrotoxicity:  0.216
Genotoxicity:  0.839 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.099 Hek293 Cytotoxicity:  0.42
BCF:   1.492
?
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:   3.672
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.43
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.034
?
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
NPO1425 Salvia palaestina Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[6677714]
NPO1425 Salvia palaestina Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1425 Salvia palaestina Species Lamiaceae 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
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae IZ < 7.0 mm PMID[6677714]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IZ < 7.0 mm PMID[6677714]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis IZ < 7.0 mm PMID[6677714]
NPT19 Organism Escherichia coli Escherichia coli IZ < 7.0 mm PMID[6677714]
NPT766 Organism Proteus vulgaris Proteus vulgaris IZ < 7.0 mm PMID[6677714]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 125.0 ug.mL-1 PMID[6677714]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MBC = 250.0 ug ml-1 PMID[6677714]

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 NPC333230 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
0.766 Intermediate Similarity NPC603362
0.76 Intermediate Similarity NPC113089
0.6923 Remote Similarity NPC77955
0.6923 Remote Similarity NPC205522
0.6923 Remote Similarity NPC215932
0.6852 Remote Similarity NPC20830
0.6545 Remote Similarity NPC69394
0.6481 Remote Similarity NPC70853
0.6429 Remote Similarity NPC604422
0.6415 Remote Similarity NPC23955
0.614 Remote Similarity NPC256612
0.614 Remote Similarity NPC283600
0.614 Remote Similarity NPC195202
0.5965 Remote Similarity NPC255350
0.5926 Remote Similarity NPC195919
0.5862 Remote Similarity NPC12200
0.5849 Remote Similarity NPC604293
0.5818 Remote Similarity NPC85233
0.5714 Remote Similarity NPC110639
0.5536 Remote Similarity NPC599976
0.5517 Remote Similarity NPC163780
0.5455 Remote Similarity NPC284424
0.5439 Remote Similarity NPC299923
0.5424 Remote Similarity NPC183597
0.5357 Remote Similarity NPC14958
0.5333 Remote Similarity NPC2476
0.5273 Remote Similarity NPC302408
0.5273 Remote Similarity NPC607644
0.5263 Remote Similarity NPC259058
0.5179 Remote Similarity NPC2771
0.5179 Remote Similarity NPC603094
0.5172 Remote Similarity NPC608264
0.5167 Remote Similarity NPC602344
0.5085 Remote Similarity NPC145379
0.5085 Remote Similarity NPC250266
0.5085 Remote Similarity NPC600010
0.5085 Remote Similarity NPC604085
0.5079 Remote Similarity NPC485299

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC333230 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
0.5965 Remote Similarity NPD2801 Pre-clinical
0.5469 Remote Similarity NPD3817 Phase 3

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