Natural Product: NPC117188

Natural Product IDNPC117188
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Corydine
IUPAC Name (6aS)-2,10,11-trimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-1-ol
Synonyms (+)-Codamine; Corydine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL489524
PubChem CID 10153
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 IDQUPXZJURZAGF-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C20H23NO4/c1-21-8-7-12-10-15(24-3)19(22)18-16(12)13(21)9-11-5-6-14(23-2)20(25-4)17(11)18/h5-6,10,13,22H,7-9H2,1-4H3/t13-/m0/s1
SMILES COc1cc2CCN([C@@H]3c2c(c1O)c1c(C3)ccc(c1OC)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   341.16 Volume:   350.589
?
Van der Waals volume.
Dense:   0.973 LogP:   2.017
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.209
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.677
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   51.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.929 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.05 Fsp3:   0.4
MCE-18:   75.571
?
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:   0.388 Fluc inhibitor:   0.068
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.514
?
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:   0.004 Promiscuous compounds:   0.803

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.012 MDCK Permeability:   -4.77
Pgp-inhibitor:   0.01 Pgp-substrate:   0.428
PAMPA:   0.113
?
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):   0.13
20% Bioavailability (F20%):   0.755 30% Bioavailability (F30%):   0.767
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.194 MRP1:   0.971
Plasma Protein Binding (PPB):   78.882% Volume Distribution (VD):   0.072
Fu: 25.283%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.843
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.249
BSEP inhibitor:   0.305

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.723 CYP2C9-substrate:   0.055
CYP2D6-inhibitor:   0.986 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.994 CYP3A4-substrate:   0.853
CYP2B6-substrate:   0.877 CYP2C8-inhibitor:   0.005
HLM stability:   0.078
?
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):  5.338 Half-life (T1/2):  2.918

ADMET: Toxicity

hERG Blockers:  0.406 hERG Blockers (10um):  0.671
Human Hepatotoxicity (H-HT):  0.524 Drug-induced Liver Injury (DILI):  0.053
AMES Toxicity:  0.656 Rat Oral Acute Toxicity:  0.727
Maximum Recommended Daily Dose:  0.899 Skin Sensitization:  0.53
Carcinogencity:  0.755 Eye Corrosion:  0.001
Eye Irritation:  0.172 Respiratory Toxicity:  0.955
Drug-induced Neurotoxicity:  0.835 Ototoxicity:  0.342
Hematotoxicity:  0.156 Drug-induced Nephrotoxicity:  0.335
Genotoxicity:  0.78 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.286 Hek293 Cytotoxicity:  0.364
BCF:   1.563
?
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:   4.084
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.581
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.78
?
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
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. fruit body n.a. PMID[10785434]
NPO22151 Stephania pierrei Species Menispermaceae Eukaryota tubers n.a. n.a. PMID[8254346]
NPO29086 Dovyalis hebecarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29246 Ixeris repens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29206 Lycopodium chinense Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22151 Stephania pierrei Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17311 Penicillium vulpinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29206 Lycopodium chinense Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29246 Ixeris repens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29086 Dovyalis hebecarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29490 Taxillus yadoriki Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17311 Penicillium vulpinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22151 Stephania pierrei Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29347 Hydnum aurantiacum Species Hydnaceae 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
NPT1371 Individual protein Cyclin-dependent kinase 2 Homo sapiens IC50 > 50000.0 nM PMID[20097066]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens IC50 > 733000.0 nM PMID[11141105]
NPT65 Cell line HepG2 Homo sapiens IC50 > 200000.0 nM PMID[29103873]
NPT165 Cell line HeLa Homo sapiens IC50 > 200000.0 nM PMID[29103873]
NPT3140 Cell line MGC-803 Homo sapiens IC50 > 200000.0 nM PMID[29103873]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum ED50 = 5800.0 ng/ml PMID[8254346]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum ED50 = 4010.0 ng/ml PMID[8254346]
NPT992 Organism Entamoeba histolytica Entamoeba histolytica IC50 = 90600.0 nM PMID[11141105]
NPT992 Organism Entamoeba histolytica Entamoeba histolytica IC50 = 30.89 ug.mL-1 DOI[10.1007/s00044-011-9767-1]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Z score = 0.52 n.a. Replenishing the malaria drug discovery pipeline: Screening and hit evaluation of the MMV Hit Generation Library 1 (HGL1) against asexual blood stage Plasmodium falciparum ,using a nano luciferase reporter read-out
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Inhibition = -4.0 % Replenishing the malaria drug discovery pipeline: Screening and hit evaluation of the MMV Hit Generation Library 1 (HGL1) against asexual blood stage Plasmodium falciparum ,using a nano luciferase reporter read-out
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 22300.0 nM PMID[11141105]

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 NPC117188 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
1.0 High Similarity NPC145832
0.7719 Intermediate Similarity NPC158376
0.7627 Intermediate Similarity NPC605949
0.75 Intermediate Similarity NPC205421
0.75 Intermediate Similarity NPC607722
0.7458 Intermediate Similarity NPC609009
0.7049 Intermediate Similarity NPC600388
0.6613 Remote Similarity NPC212794
0.6613 Remote Similarity NPC606254
0.6567 Remote Similarity NPC114364
0.6406 Remote Similarity NPC247389
0.6364 Remote Similarity NPC199465
0.6154 Remote Similarity NPC474931
0.6 Remote Similarity NPC136508
0.5571 Remote Similarity NPC320223
0.5538 Remote Similarity NPC326316
0.5538 Remote Similarity NPC81733
0.5469 Remote Similarity NPC99659
0.5469 Remote Similarity NPC325871
0.5352 Remote Similarity NPC610764
0.5325 Remote Similarity NPC609914
0.5294 Remote Similarity NPC253043
0.5286 Remote Similarity NPC219341
0.5278 Remote Similarity NPC128560
0.5278 Remote Similarity NPC229166
0.5147 Remote Similarity NPC608930
0.5139 Remote Similarity NPC600118
0.5075 Remote Similarity NPC13504
0.5072 Remote Similarity NPC195075
0.5072 Remote Similarity NPC27410

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC117188 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