Natural Product: NPC606254

Natural Product IDNPC606254
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PLEOQAHCVRVCDL-ZDUSSCGKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1316470
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 PLEOQAHCVRVCDL-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C19H21NO4/c1-20-5-4-10-7-16(24-3)19(22)18-12-9-14(21)15(23-2)8-11(12)6-13(20)17(10)18/h7-9,13,21-22H,4-6H2,1-3H3/t13-/m0/s1
SMILES COc1cc2c(cc1O)-c1c(O)c(OC)cc3c1[C@H](C2)N(C)CC3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   327.15 Volume:   333.293
?
Van der Waals volume.
Dense:   0.982 LogP:   1.613
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.871
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.478
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   62.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.888 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.111 Fsp3:   0.368
MCE-18:   76.077
?
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:   0.66 Fluc inhibitor:   0.036
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.696
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.366
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.831

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.136 MDCK Permeability:   -4.82
Pgp-inhibitor:   0.006 Pgp-substrate:   0.685
PAMPA:   0.025
?
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):   0.102
20% Bioavailability (F20%):   0.895 30% Bioavailability (F30%):   0.959
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.085 MRP1:   0.967
Plasma Protein Binding (PPB):   75.012% Volume Distribution (VD):   -0.134
Fu: 26.774%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.698
BSEP inhibitor:   0.233

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   0.375
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.933 CYP3A4-substrate:   0.29
CYP2B6-substrate:   0.962 CYP2C8-inhibitor:   0.302
HLM stability:   0.41
?
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):  5.376 Half-life (T1/2):  2.608

ADMET: Toxicity

hERG Blockers:  0.346 hERG Blockers (10um):  0.687
Human Hepatotoxicity (H-HT):  0.549 Drug-induced Liver Injury (DILI):  0.045
AMES Toxicity:  0.666 Rat Oral Acute Toxicity:  0.745
Maximum Recommended Daily Dose:  0.931 Skin Sensitization:  0.72
Carcinogencity:  0.657 Eye Corrosion:  0.0
Eye Irritation:  0.176 Respiratory Toxicity:  0.964
Drug-induced Neurotoxicity:  0.741 Ototoxicity:  0.377
Hematotoxicity:  0.106 Drug-induced Nephrotoxicity:  0.298
Genotoxicity:  0.888 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.453 Hek293 Cytotoxicity:  0.455
BCF:   1.26
?
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:   3.918
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.033
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.451
?
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
NPO29391 Papaver bracteatum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[17226487]
NPO29391 Papaver bracteatum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12093 Papaver orientale Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3714 Papaver pseudo-orientale Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46809 Corydalis gortschakovii Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29391 Papaver bracteatum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29391 Papaver bracteatum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3714 Papaver pseudo-orientale Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12093 Papaver orientale Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29391 Papaver bracteatum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12093 Papaver orientale Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29391 Papaver bracteatum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3714 Papaver pseudo-orientale Species Papaveraceae 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
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT277 Individual protein Caspase-1 Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens Potency = 2511.9 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 19952.6 nM PubChem BioAssay data set
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 1122.0 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 29855.4 nM PubChem BioAssay data set
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 9976.3 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT583 Individual protein Inositol monophosphatase 1 Rattus norvegicus Potency = 14125.4 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 22387.2 nM PubChem BioAssay data set
NPT583 Individual protein Inositol monophosphatase 1 Rattus norvegicus Potency = 15848.9 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 50118.7 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. Potency = 14125.4 nM PubChem BioAssay data set

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 NPC606254 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
0.7586 Intermediate Similarity NPC212794
0.7 Intermediate Similarity NPC609009
0.6984 Remote Similarity NPC199465
0.6949 Remote Similarity NPC158376
0.6769 Remote Similarity NPC128560
0.6613 Remote Similarity NPC117188
0.6613 Remote Similarity NPC145832
0.6613 Remote Similarity NPC605949
0.6 Remote Similarity NPC205421
0.6 Remote Similarity NPC607722
0.5846 Remote Similarity NPC253043
0.5846 Remote Similarity NPC136508
0.5625 Remote Similarity NPC13504
0.56 Remote Similarity NPC609914
0.5522 Remote Similarity NPC474931
0.5493 Remote Similarity NPC114364
0.5373 Remote Similarity NPC195075
0.5373 Remote Similarity NPC27410
0.5352 Remote Similarity NPC229166
0.5312 Remote Similarity NPC99659
0.5312 Remote Similarity NPC325871
0.5147 Remote Similarity NPC600388

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC606254 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