Natural Product: NPC603823

Natural Product IDNPC603823
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WCJNJWNPAYBQPW-VIFPVBQESA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL451891
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 WCJNJWNPAYBQPW-VIFPVBQESA-N
Standard InCHI InChI=1S/C16H18O2/c1-9-6-5-7-12-13(9)11(3)14-10(2)8-18-16(14)15(12)17-4/h5,7-9H,6H2,1-4H3/t9-/m0/s1
SMILES COc1c2c(c(C)c3c(C)coc13)[C@@H](C)CC=C2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   242.13 Volume:   264.021
?
Van der Waals volume.
Dense:   0.917 LogP:   4.086
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.534
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.95
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   15.0
TPSA:   22.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.73 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.678 Fsp3:   0.375
MCE-18:   54.091
?
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:   0.524 Fluc inhibitor:   0.71
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.756
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.464
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.585 Promiscuous compounds:   0.187

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.598 MDCK Permeability:   -4.511
Pgp-inhibitor:   0.919 Pgp-substrate:   0.462
PAMPA:   0.023
?
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):   0.001
20% Bioavailability (F20%):   0.27 30% Bioavailability (F30%):   0.372
50% Bioavailability (F50%):   0.713

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.781 MRP1:   0.997
Plasma Protein Binding (PPB):   96.711% Volume Distribution (VD):   0.229
Fu: 3.706%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.906 BCRP inhibitor:   0.219
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.967 CYP1A2-substrate:   0.928
CYP2C19-inhibitor:   0.899 CYP2C19-substrate:   0.936
CYP2C9-inhibitor:   0.521 CYP2C9-substrate:   0.063
CYP2D6-inhibitor:   0.391 CYP2D6-substrate:   0.922
CYP3A4-inhibitor:   0.798 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.225 CYP2C8-inhibitor:   0.999
HLM stability:   0.879
?
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):  8.757 Half-life (T1/2):  0.383

ADMET: Toxicity

hERG Blockers:  0.118 hERG Blockers (10um):  0.441
Human Hepatotoxicity (H-HT):  0.766 Drug-induced Liver Injury (DILI):  0.853
AMES Toxicity:  0.749 Rat Oral Acute Toxicity:  0.696
Maximum Recommended Daily Dose:  0.832 Skin Sensitization:  0.815
Carcinogencity:  0.881 Eye Corrosion:  0.294
Eye Irritation:  0.951 Respiratory Toxicity:  0.868
Drug-induced Neurotoxicity:  0.562 Ototoxicity:  0.39
Hematotoxicity:  0.499 Drug-induced Nephrotoxicity:  0.414
Genotoxicity:  0.352 RPMI-8226 Immunitoxicity:  0.134
A549 Cytotoxicity:  0.291 Hek293 Cytotoxicity:  0.32
BCF:   2.676
?
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:   4.187
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.851
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.742
?
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
NPO28557 Cacalia hastata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28557 Cacalia hastata Species Asteraceae 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
NPT172 Organism Proteus mirabilis Proteus mirabilis MIC > 400.0 ug.mL-1 PMID[11325222]
NPT20 Organism Candida albicans Candida albicans MIC > 400.0 ug.mL-1 PMID[11325222]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 400.0 ug.mL-1 PMID[11325222]
NPT19 Organism Escherichia coli Escherichia coli MIC > 400.0 ug.mL-1 PMID[11325222]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 400.0 ug.mL-1 PMID[11325222]

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
- Artemia salina LD50 > 1000.0 ppm PMID[11325222]

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 NPC603823 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
0.6667 Remote Similarity NPC484397
0.6379 Remote Similarity NPC191012
0.625 Remote Similarity NPC484398
0.6207 Remote Similarity NPC484399
0.5968 Remote Similarity NPC132054
0.5606 Remote Similarity NPC484406
0.5455 Remote Similarity NPC484400
0.5072 Remote Similarity NPC298071

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603823 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