Natural Product: NPC320223

Natural Product IDNPC320223
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WOIZHRXESCUSGM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3194830
PubChem CID 3083908
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

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 WOIZHRXESCUSGM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H19NO4/c1-20-6-5-11-8-14-19(24-9-23-14)17-15(11)12(20)7-10-3-4-13(21)18(22-2)16(10)17/h3-4,8,12,21H,5-7,9H2,1-2H3
SMILES CN1CCC2=CC3=C(C4=C2C1CC5=C4C(=C(C=C5)O)OC)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   325.13 Volume:   324.737
?
Van der Waals volume.
Dense:   1.001 LogP:   2.243
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.317
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.142
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   51.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.874 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.3 Fsp3:   0.368
MCE-18:   88.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.814 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.671
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.436
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.31

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.675 MDCK Permeability:   -4.714
Pgp-inhibitor:   0.088 Pgp-substrate:   0.147
PAMPA:   0.097
?
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):   0.003
20% Bioavailability (F20%):   0.142 30% Bioavailability (F30%):   0.076
50% Bioavailability (F50%):   0.849

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.945 MRP1:   0.955
Plasma Protein Binding (PPB):   65.256% Volume Distribution (VD):   0.248
Fu: 36.737%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.532
OATP1B3 inhibitor:   0.871 BCRP inhibitor:   0.293
BSEP inhibitor:   0.83

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.988 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.812
CYP3A4-inhibitor:   0.954 CYP3A4-substrate:   0.927
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.135
?
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):  8.088 Half-life (T1/2):  1.608

ADMET: Toxicity

hERG Blockers:  0.516 hERG Blockers (10um):  0.676
Human Hepatotoxicity (H-HT):  0.467 Drug-induced Liver Injury (DILI):  0.013
AMES Toxicity:  0.798 Rat Oral Acute Toxicity:  0.548
Maximum Recommended Daily Dose:  0.844 Skin Sensitization:  0.943
Carcinogencity:  0.87 Eye Corrosion:  0.0
Eye Irritation:  0.097 Respiratory Toxicity:  0.969
Drug-induced Neurotoxicity:  0.539 Ototoxicity:  0.72
Hematotoxicity:  0.13 Drug-induced Nephrotoxicity:  0.115
Genotoxicity:  0.517 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.193 Hek293 Cytotoxicity:  0.559
BCF:   1.573
?
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:   3.979
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.671
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.755
?
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
NPO2204 Lindera megaphylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2204 Lindera megaphylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2204 Lindera megaphylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2204 Lindera megaphylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2204 Lindera megaphylla Species Lauraceae 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
NPT1474 Individual protein ATP-dependent Clp protease proteolytic subunit Bacillus subtilis (strain 168) Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 316.2 nM PubChem BioAssay data set
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT446 Individual protein Rap guanine nucleotide exchange factor 3 Homo sapiens Potency n.a. 5623.4 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 32642.7 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set

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 NPC320223 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
0.746 Intermediate Similarity NPC247389
0.7273 Intermediate Similarity NPC600118
0.7231 Intermediate Similarity NPC219341
0.7164 Intermediate Similarity NPC128560
0.7164 Intermediate Similarity NPC229166
0.7059 Intermediate Similarity NPC114364
0.7015 Intermediate Similarity NPC610764
0.6765 Remote Similarity NPC298979
0.6667 Remote Similarity NPC63997
0.6667 Remote Similarity NPC16805
0.6667 Remote Similarity NPC167546
0.6615 Remote Similarity NPC609009
0.6471 Remote Similarity NPC266753
0.6471 Remote Similarity NPC160298
0.6471 Remote Similarity NPC605845
0.6418 Remote Similarity NPC306902
0.6418 Remote Similarity NPC232924
0.6176 Remote Similarity NPC474931
0.6029 Remote Similarity NPC600388
0.6 Remote Similarity NPC476432
0.6 Remote Similarity NPC24264
0.6 Remote Similarity NPC19520
0.5797 Remote Similarity NPC136508
0.5714 Remote Similarity NPC205421
0.5714 Remote Similarity NPC607722
0.5694 Remote Similarity NPC199465
0.5571 Remote Similarity NPC117188
0.5571 Remote Similarity NPC145832
0.5571 Remote Similarity NPC253043
0.5362 Remote Similarity NPC326316
0.5362 Remote Similarity NPC13504
0.5362 Remote Similarity NPC81733
0.5352 Remote Similarity NPC195075
0.5352 Remote Similarity NPC27410
0.5294 Remote Similarity NPC99659
0.5294 Remote Similarity NPC325871
0.5205 Remote Similarity NPC606650
0.5143 Remote Similarity NPC158376
0.5139 Remote Similarity NPC605949
0.5135 Remote Similarity NPC126284
0.5135 Remote Similarity NPC226102
0.5135 Remote Similarity NPC261206

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC320223 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