Natural Product: NPC233599

Natural Product IDNPC233599
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RISOXQXSFOVFBL-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14926725
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000253] Stilbenes

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 RISOXQXSFOVFBL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H18O2/c1-17-15-10-8-13(9-11-15)6-7-14-4-3-5-16(12-14)18-2/h3-5,8-12H,6-7H2,1-2H3
SMILES COc1ccc(CCc2cccc(c2)OC)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   242.13 Volume:   269.941
?
Van der Waals volume.
Dense:   0.897 LogP:   4.288
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.992
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.394
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   18.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.799 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.424 Fsp3:   0.25
MCE-18:   10.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.63 Fluc inhibitor:   0.794
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.04
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.403
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.978 Promiscuous compounds:   0.141

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.887 MDCK Permeability:   -4.691
Pgp-inhibitor:   0.991 Pgp-substrate:   0.044
PAMPA:   0.003
?
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):   0.46
20% Bioavailability (F20%):   0.486 30% Bioavailability (F30%):   0.57
50% Bioavailability (F50%):   0.618

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.053 MRP1:   0.246
Plasma Protein Binding (PPB):   94.107% Volume Distribution (VD):   0.209
Fu: 2.77%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.959
OATP1B3 inhibitor:   0.891 BCRP inhibitor:   0.631
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.956
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.971
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.696
CYP2B6-substrate:   0.971 CYP2C8-inhibitor:   0.999
HLM stability:   0.996
?
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):  10.748 Half-life (T1/2):  0.442

ADMET: Toxicity

hERG Blockers:  0.702 hERG Blockers (10um):  0.847
Human Hepatotoxicity (H-HT):  0.596 Drug-induced Liver Injury (DILI):  0.391
AMES Toxicity:  0.628 Rat Oral Acute Toxicity:  0.126
Maximum Recommended Daily Dose:  0.419 Skin Sensitization:  0.554
Carcinogencity:  0.412 Eye Corrosion:  0.331
Eye Irritation:  0.919 Respiratory Toxicity:  0.65
Drug-induced Neurotoxicity:  0.693 Ototoxicity:  0.465
Hematotoxicity:  0.427 Drug-induced Nephrotoxicity:  0.734
Genotoxicity:  0.029 RPMI-8226 Immunitoxicity:  0.096
A549 Cytotoxicity:  0.4 Hek293 Cytotoxicity:  0.571
BCF:   2.475
?
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:   4.231
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.764
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.184
?
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
NPO33038 plagiochila stephensoniana Species Plagiochilaceae Eukaryota n.a. New Zealand n.a. PMID[8254344]

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
NPT4923 Organism Trichostrongylus colubriformis Trichostrongylus colubriformis Inhibition = 85.0 % PMID[29019405]

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 NPC233599 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
0.75 Intermediate Similarity NPC2682
0.7297 Intermediate Similarity NPC475852
0.6944 Remote Similarity NPC75440
0.6154 Remote Similarity NPC53906
0.5882 Remote Similarity NPC299759
0.5854 Remote Similarity NPC221077
0.5833 Remote Similarity NPC475961
0.5833 Remote Similarity NPC21890
0.5789 Remote Similarity NPC604144
0.5676 Remote Similarity NPC233410
0.5278 Remote Similarity NPC254625
0.5263 Remote Similarity NPC608070
0.52 Remote Similarity NPC17837
0.5152 Remote Similarity NPC71853
0.5143 Remote Similarity NPC1065

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC233599 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