Natural Product: NPC114364

Natural Product IDNPC114364
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-Bulbocapnine
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL157912
PubChem CID 12441
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 LODGIKWNLDQZBM-LBPRGKRZSA-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(22-2)18(21)16(10)17/h3-4,8,12,21H,5-7,9H2,1-2H3/t12-/m0/s1
SMILES CN1CCc2cc3c(c4-c5c(ccc(c5O)OC)C[C@H]1c24)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   325.13 Volume:   324.737
?
Van der Waals volume.
Dense:   1.001 LogP:   2.07
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.17
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.906
?
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:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.26 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:   0.716 Fluc inhibitor:   0.041
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.613
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.455
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.461

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.922 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.054 Pgp-substrate:   0.426
PAMPA:   0.068
?
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):   0.032
20% Bioavailability (F20%):   0.264 30% Bioavailability (F30%):   0.324
50% Bioavailability (F50%):   0.923

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.769 MRP1:   0.932
Plasma Protein Binding (PPB):   79.432% Volume Distribution (VD):   0.026
Fu: 24.823%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.77
OATP1B3 inhibitor:   0.666 BCRP inhibitor:   0.252
BSEP inhibitor:   0.554

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.302
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   0.01
CYP2C9-inhibitor:   0.991 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.281
CYP3A4-inhibitor:   0.947 CYP3A4-substrate:   0.984
CYP2B6-substrate:   0.998 CYP2C8-inhibitor:   0.0
HLM stability:   0.324
?
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):  6.521 Half-life (T1/2):  1.994

ADMET: Toxicity

hERG Blockers:  0.397 hERG Blockers (10um):  0.645
Human Hepatotoxicity (H-HT):  0.576 Drug-induced Liver Injury (DILI):  0.119
AMES Toxicity:  0.737 Rat Oral Acute Toxicity:  0.703
Maximum Recommended Daily Dose:  0.937 Skin Sensitization:  0.537
Carcinogencity:  0.836 Eye Corrosion:  0.001
Eye Irritation:  0.205 Respiratory Toxicity:  0.949
Drug-induced Neurotoxicity:  0.832 Ototoxicity:  0.33
Hematotoxicity:  0.172 Drug-induced Nephrotoxicity:  0.429
Genotoxicity:  0.907 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.324 Hek293 Cytotoxicity:  0.405
BCF:   1.652
?
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:   4.168
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.611
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.948
?
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]
NPO2020 Corydalis cava Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22029392]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. root n.a. PMID[24317429]
NPO14045 Corydalis decumbens Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[31599578]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[38415909]
NPO23076 Illigera luzonensis Species Hernandiaceae Eukaryota n.a. n.a. n.a. PMID[9214740]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10246 Fumaria officinalis Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22727 Avena fatua Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21569 Helichrysum fulvum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16798 Piper sylvaticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17311 Penicillium vulpinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31490 Corydalis bulbosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2020 Corydalis cava Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23076 Illigera luzonensis Species Hernandiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12143 Corydalis solida Species Papaveraceae 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]
NPO14045 Corydalis decumbens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2020 Corydalis cava Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31490 Corydalis bulbosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24092 Glaucium pulchrum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11840 Corydalis caucasica 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]
NPO14045 Corydalis decumbens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19840 Corydalis marschalliana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10246 Fumaria officinalis Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12143 Corydalis solida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2020 Corydalis cava Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14045 Corydalis decumbens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10246 Fumaria officinalis Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24092 Glaucium pulchrum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19840 Corydalis marschalliana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11840 Corydalis caucasica 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]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14045 Corydalis decumbens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31490 Corydalis bulbosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14045 Corydalis decumbens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17311 Penicillium vulpinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28926 Corydalis tuberosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21569 Helichrysum fulvum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29263 Tylopilus plumbeoviolaceus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29347 Hydnum aurantiacum Species Hydnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29206 Lycopodium chinense Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11840 Corydalis caucasica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24092 Glaucium pulchrum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29441 Eremophila oppositifolia Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22727 Avena fatua Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29490 Taxillus yadoriki Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19840 Corydalis marschalliana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23076 Illigera luzonensis Species Hernandiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12143 Corydalis solida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16798 Piper sylvaticum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14045 Corydalis decumbens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29086 Dovyalis hebecarpa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10246 Fumaria officinalis Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29246 Ixeris repens Species Asteraceae 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
NPT1857 Individual protein Dopamine D1 receptor Rattus norvegicus IC50 = 739.0 nM PMID[2405158]
NPT1858 Individual protein Dopamine D2 receptor Rattus norvegicus IC50 = 14047.0 nM PMID[2405158]
NPT1857 Individual protein Dopamine D1 receptor Rattus norvegicus IC50 = 740.0 nM PMID[17228858]
NPT1858 Individual protein Dopamine D2 receptor Rattus norvegicus IC50 = 14000.0 nM PMID[17228858]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT681 Cell line PC-12 Rattus norvegicus IC50 = 27000.0 nM PMID[17228858]
NPT28438 Unchecked Unchecked n.a. IC50 = 12900.0 nM PMID[37172474]
NPT28438 Unchecked Unchecked n.a. IC50 = 11600.0 nM PMID[37172474]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 86.8 % PMID[9214740]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 89.3 % PMID[9214740]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 83.2 % PMID[9214740]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 86.6 % PMID[9214740]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition = 24.4 % PMID[2405158]
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition = 85.1 % PMID[2405158]





 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 NPC114364 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
0.8361 Intermediate Similarity NPC205421
0.8361 Intermediate Similarity NPC607722
0.7313 Intermediate Similarity NPC610764
0.7231 Intermediate Similarity NPC247389
0.7143 Intermediate Similarity NPC158376
0.7059 Intermediate Similarity NPC320223
0.6957 Remote Similarity NPC128560
0.6957 Remote Similarity NPC229166
0.6812 Remote Similarity NPC600118
0.6765 Remote Similarity NPC219341
0.6567 Remote Similarity NPC117188
0.6567 Remote Similarity NPC145832
0.6522 Remote Similarity NPC266753
0.6522 Remote Similarity NPC160298
0.6471 Remote Similarity NPC63997
0.6471 Remote Similarity NPC16805
0.6471 Remote Similarity NPC474931
0.6471 Remote Similarity NPC167546
0.6429 Remote Similarity NPC199465
0.6338 Remote Similarity NPC298979
0.6232 Remote Similarity NPC306902
0.6232 Remote Similarity NPC232924
0.6056 Remote Similarity NPC476432
0.6056 Remote Similarity NPC24264
0.6056 Remote Similarity NPC605845
0.5857 Remote Similarity NPC605949
0.5833 Remote Similarity NPC19520
0.5714 Remote Similarity NPC609009
0.5634 Remote Similarity NPC136508
0.5634 Remote Similarity NPC600388
0.5493 Remote Similarity NPC212794
0.5493 Remote Similarity NPC606254
0.5263 Remote Similarity NPC135772
0.5211 Remote Similarity NPC326316
0.5211 Remote Similarity NPC81733
0.5143 Remote Similarity NPC99659
0.5143 Remote Similarity NPC325871
0.5065 Remote Similarity NPC248642

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC114364 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