Natural Product: NPC158376

Natural Product IDNPC158376
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Corytuberine
IUPAC Name (6aS)-2,10-dimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-1,11-diol
Synonyms Corytuberine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL227965
PubChem CID 160500
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 WHFUDAOCYRYAKQ-LBPRGKRZSA-N
Standard InCHI InChI=1S/C19H21NO4/c1-20-7-6-11-9-14(24-3)19(22)17-15(11)12(20)8-10-4-5-13(23-2)18(21)16(10)17/h4-5,9,12,21-22H,6-8H2,1-3H3/t12-/m0/s1
SMILES COc1ccc2c(c1O)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:   1.57
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.807
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.517
?
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:   3.137 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:   0.501 Fluc inhibitor:   0.087
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.509
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.49
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.85

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.177 MDCK Permeability:   -4.828
Pgp-inhibitor:   0.006 Pgp-substrate:   0.172
PAMPA:   0.239
?
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):   0.33
20% Bioavailability (F20%):   0.678 30% Bioavailability (F30%):   0.722
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.036 MRP1:   0.967
Plasma Protein Binding (PPB):   80.112% Volume Distribution (VD):   -0.079
Fu: 22.265%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.933
OATP1B3 inhibitor:   0.931 BCRP inhibitor:   0.095
BSEP inhibitor:   0.109

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.053
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.99 CYP2C9-substrate:   0.179
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.978 CYP3A4-substrate:   0.51
CYP2B6-substrate:   0.485 CYP2C8-inhibitor:   0.011
HLM stability:   0.673
?
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):  5.052 Half-life (T1/2):  2.796

ADMET: Toxicity

hERG Blockers:  0.315 hERG Blockers (10um):  0.637
Human Hepatotoxicity (H-HT):  0.541 Drug-induced Liver Injury (DILI):  0.084
AMES Toxicity:  0.687 Rat Oral Acute Toxicity:  0.73
Maximum Recommended Daily Dose:  0.924 Skin Sensitization:  0.625
Carcinogencity:  0.716 Eye Corrosion:  0.001
Eye Irritation:  0.277 Respiratory Toxicity:  0.973
Drug-induced Neurotoxicity:  0.751 Ototoxicity:  0.365
Hematotoxicity:  0.128 Drug-induced Nephrotoxicity:  0.356
Genotoxicity:  0.845 RPMI-8226 Immunitoxicity:  0.109
A549 Cytotoxicity:  0.466 Hek293 Cytotoxicity:  0.417
BCF:   1.313
?
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:   4.088
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.091
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.667
?
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
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20020118]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1556/abot.45.2003.3-4.15]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. fruit body n.a. PMID[10785434]
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[10978218]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[15019787]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[1659613]
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota stem n.a. n.a. PMID[17081761]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota stem bark n.a. n.a. PMID[17918910]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. stem n.a. PMID[18175990]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota Stems; Barks n.a. n.a. PMID[19086868]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22029392]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[23517479]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. bark n.a. PMID[23823874]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[28485933]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[37685099]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1005 Pycnarrhena novoguineensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2466 Aloe microstigma Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7312 Aplidium multiplicatum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10176 Chrozophora prostrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11791 Magnolia obovata Species Magnoliaceae 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[COCONUT]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29206 Lycopodium chinense Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29246 Ixeris repens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29086 Dovyalis hebecarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5075 Balaenoptera borealis Species Balaenopteridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7312 Aplidium multiplicatum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2466 Aloe microstigma Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1005 Pycnarrhena novoguineensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29347 Hydnum aurantiacum Species Hydnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10176 Chrozophora prostrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29490 Taxillus yadoriki Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3020 Brickellia paniculata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17311 Penicillium vulpinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29206 Lycopodium chinense Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1518 Pedicularis chinensis Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2556 Platytaenia dasycarpa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15671 Iris decora Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae 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]

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
NPT1076 Cell line B-cells n.a. IC50 = 21300.0 nM PMID[17081761]
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]
NPT2 Others Unspecified n.a. IC50 = 23200.0 nM PMID[17081761]
NPT2 Others Unspecified n.a. Ratio CC50/IC50 > 4.0 n.a. PMID[17081761]

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 NPC158376 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
0.7895 Intermediate Similarity NPC205421
0.7895 Intermediate Similarity NPC607722
0.7719 Intermediate Similarity NPC117188
0.7719 Intermediate Similarity NPC145832
0.7414 Intermediate Similarity NPC605949
0.7241 Intermediate Similarity NPC609009
0.7143 Intermediate Similarity NPC114364
0.6949 Remote Similarity NPC212794
0.6949 Remote Similarity NPC606254
0.6406 Remote Similarity NPC199465
0.619 Remote Similarity NPC474931
0.5781 Remote Similarity NPC600388
0.5541 Remote Similarity NPC609914
0.5538 Remote Similarity NPC136508
0.5312 Remote Similarity NPC13504
0.5303 Remote Similarity NPC195075
0.5303 Remote Similarity NPC253043
0.5303 Remote Similarity NPC27410
0.5224 Remote Similarity NPC247389
0.5143 Remote Similarity NPC320223
0.5143 Remote Similarity NPC610764
0.5077 Remote Similarity NPC326316
0.5077 Remote Similarity NPC81733
0.507 Remote Similarity NPC128560
0.507 Remote Similarity NPC229166

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC158376 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