Natural Product: NPC605949

Natural Product IDNPC605949
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RQCOQZNIQLKGTN-ZDUSSCGKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL5091026
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 RQCOQZNIQLKGTN-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C19H21NO3/c1-20-8-7-12-10-15(23-3)19(21)18-16(12)13(20)9-11-5-4-6-14(22-2)17(11)18/h4-6,10,13,21H,7-9H2,1-3H3/t13-/m0/s1
SMILES COc1cc2c3c(c1O)-c1c(cccc1OC)C[C@@H]3N(C)CC2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   311.15 Volume:   324.503
?
Van der Waals volume.
Dense:   0.959 LogP:   2.367
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.314
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.919
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   41.93
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.925 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.991 Fsp3:   0.368
MCE-18:   72.769
?
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:   0.512 Fluc inhibitor:   0.111
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.57
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.477
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.671

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.899 MDCK Permeability:   -4.765
Pgp-inhibitor:   0.01 Pgp-substrate:   0.554
PAMPA:   0.081
?
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):   0.121
20% Bioavailability (F20%):   0.875 30% Bioavailability (F30%):   0.904
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.134 MRP1:   0.947
Plasma Protein Binding (PPB):   84.115% Volume Distribution (VD):   0.222
Fu: 17.189%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.836
OATP1B3 inhibitor:   0.879 BCRP inhibitor:   0.219
BSEP inhibitor:   0.431

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.026
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.734 CYP2C9-substrate:   0.783
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.019
CYP3A4-inhibitor:   0.976 CYP3A4-substrate:   0.782
CYP2B6-substrate:   0.961 CYP2C8-inhibitor:   0.002
HLM stability:   0.182
?
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):  6.565 Half-life (T1/2):  2.281

ADMET: Toxicity

hERG Blockers:  0.429 hERG Blockers (10um):  0.667
Human Hepatotoxicity (H-HT):  0.555 Drug-induced Liver Injury (DILI):  0.073
AMES Toxicity:  0.726 Rat Oral Acute Toxicity:  0.731
Maximum Recommended Daily Dose:  0.901 Skin Sensitization:  0.569
Carcinogencity:  0.776 Eye Corrosion:  0.001
Eye Irritation:  0.208 Respiratory Toxicity:  0.959
Drug-induced Neurotoxicity:  0.855 Ototoxicity:  0.344
Hematotoxicity:  0.15 Drug-induced Nephrotoxicity:  0.352
Genotoxicity:  0.833 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.312 Hek293 Cytotoxicity:  0.38
BCF:   1.503
?
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:   4.076
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.332
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.739
?
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]
NPO47029 Papaver macrantha Genus Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12093 Papaver orientale Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54417 Papaver orientalis Genus 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]
NPO47530 Papaver pseudorientale Genus 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens Ki n.a. n.a. n.a. PMID[34910498]
NPT204 Individual protein Acetylcholinesterase Homo sapiens IC50 n.a. n.a. n.a. PMID[34910498]
NPT67 Individual protein Cholinesterase Equus caballus Ki = 600.0 nM PMID[34910498]
NPT67 Individual protein Cholinesterase Equus caballus IC50 = 2800.0 nM PMID[34910498]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus IC50 = 260000.0 nM PMID[34910498]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Ki = 68000.0 nM PMID[34910498]

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 NPC605949 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
0.7627 Intermediate Similarity NPC117188
0.7627 Intermediate Similarity NPC145832
0.7458 Intermediate Similarity NPC609009
0.7414 Intermediate Similarity NPC158376
0.6613 Remote Similarity NPC212794
0.6613 Remote Similarity NPC606254
0.6406 Remote Similarity NPC205421
0.6406 Remote Similarity NPC607722
0.6212 Remote Similarity NPC219341
0.6119 Remote Similarity NPC199465
0.5857 Remote Similarity NPC114364
0.5522 Remote Similarity NPC195075
0.5522 Remote Similarity NPC27410
0.5522 Remote Similarity NPC600388
0.5441 Remote Similarity NPC474931
0.5325 Remote Similarity NPC609914
0.5303 Remote Similarity NPC326316
0.5303 Remote Similarity NPC81733
0.5294 Remote Similarity NPC136508
0.5152 Remote Similarity NPC470925
0.5139 Remote Similarity NPC320223
0.5075 Remote Similarity NPC13504
0.5072 Remote Similarity NPC168753
0.5072 Remote Similarity NPC253043
0.5072 Remote Similarity NPC118274

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605949 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