Natural Product: NPC303581

Natural Product IDNPC303581
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XPOJSWHIKCNLEQ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms NSC-32984
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1339015
PubChem CID 72616
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002743] Protopine alkaloids

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 XPOJSWHIKCNLEQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H23NO5/c1-22-7-6-14-9-19(24-2)20(25-3)10-15(14)17(23)8-13-4-5-18-21(16(13)11-22)27-12-26-18/h4-5,9-10H,6-8,11-12H2,1-3H3
SMILES COc1cc2C(=O)Cc3ccc4c(c3CN(CCc2cc1OC)C)OCO4

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   369.16 Volume:   374.039
?
Van der Waals volume.
Dense:   0.987 LogP:   1.773
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.146
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.811
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   25.0
TPSA:   57.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.811 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.03 Fsp3:   0.381
MCE-18:   51.586
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.14 Fluc inhibitor:   0.098
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.651
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.129
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.228

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.656 MDCK Permeability:   -4.757
Pgp-inhibitor:   0.385 Pgp-substrate:   0.026
PAMPA:   0.007
?
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):   0.0
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.66

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.859 MRP1:   0.905
Plasma Protein Binding (PPB):   78.49% Volume Distribution (VD):   0.337
Fu: 22.078%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.851
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.35
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.004
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.727 CYP2C9-substrate:   0.975
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.906
CYP3A4-inhibitor:   0.902 CYP3A4-substrate:   0.267
CYP2B6-substrate:   0.439 CYP2C8-inhibitor:   0.0
HLM stability:   0.163
?
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):  8.889 Half-life (T1/2):  2.239

ADMET: Toxicity

hERG Blockers:  0.484 hERG Blockers (10um):  0.604
Human Hepatotoxicity (H-HT):  0.715 Drug-induced Liver Injury (DILI):  0.372
AMES Toxicity:  0.66 Rat Oral Acute Toxicity:  0.795
Maximum Recommended Daily Dose:  0.778 Skin Sensitization:  0.736
Carcinogencity:  0.902 Eye Corrosion:  0.002
Eye Irritation:  0.078 Respiratory Toxicity:  0.91
Drug-induced Neurotoxicity:  0.906 Ototoxicity:  0.486
Hematotoxicity:  0.749 Drug-induced Nephrotoxicity:  0.697
Genotoxicity:  0.976 RPMI-8226 Immunitoxicity:  0.142
A549 Cytotoxicity:  0.253 Hek293 Cytotoxicity:  0.512
BCF:   1.135
?
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:   3.58
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.893
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.168
?
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]
NPO14337 Ecklonia stolonifera Species Lessoniaceae Eukaryota n.a. n.a. n.a. PMID[12913249]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[15019787]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[21094631]
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]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[37685099]
NPO29868 Dicentra spectabilis Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae 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]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13637 Thalictrum foliolosum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30288 Thalictrum thunbergii Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26963 Sarcocapnos enneaphylla Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12540 Fuligo septica Species Physaraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14337 Ecklonia stolonifera Species Lessoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15522 Michelia fuscata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11457 Chelidonium majus Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10176 Chrozophora prostrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6137 Lepista glaucocana Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Latex Exudate 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 n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO13637 Thalictrum foliolosum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22043 Hylomecon japonica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30288 Thalictrum thunbergii Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29868 Dicentra spectabilis Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14337 Ecklonia stolonifera Species Lessoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11457 Chelidonium majus Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19361 Herba meconpsis integrifoliae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14337 Ecklonia stolonifera Species Lessoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11457 Chelidonium majus 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]
NPO13637 Thalictrum foliolosum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22043 Hylomecon japonica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11457 Chelidonium majus Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30288 Thalictrum thunbergii Species Ranunculaceae 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]
NPO31048 Papaver sommiferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22043 Hylomecon japonica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13637 Thalictrum foliolosum Species Ranunculaceae 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]
NPO29868 Dicentra spectabilis 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]
NPO11457 Chelidonium majus Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13235 Berberis chitria Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22043 Hylomecon japonica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7312 Aplidium multiplicatum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2466 Aloe microstigma Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16670 Centaurea sclerolepis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15522 Michelia fuscata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7063 Gentianella amarella Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28372 Corydalis pallida Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15455 Karwinskia johnstonii Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10176 Chrozophora prostrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13637 Thalictrum foliolosum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15415 Othonna obtusiloba Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14659 Cereus pecten-aboriginum Species Sagartiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26963 Sarcocapnos enneaphylla Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26740 Tolypothrix distorta Species Tolypothrichaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO14337 Ecklonia stolonifera Species Lessoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2826 Pseudocercospora cruenta Species Mycosphaerellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12540 Fuligo septica Species Physaraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9511 Ranunculus serbicus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6137 Lepista glaucocana Species Tricholomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16169 Sedum altissimum Species Crassulaceae 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
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens Potency = 25.1 nM PubChem BioAssay data set
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 141253.8 nM PubChem BioAssay data set
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 10417.9 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 9285.0 nM PubChem BioAssay data set
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae Inhibition = 9.37 % DOI[10.6019/CHEMBL4296182]
NPT20 Organism Candida albicans Candida albicans Inhibition = -0.52 % DOI[10.6019/CHEMBL4296182]
NPT19 Organism Escherichia coli Escherichia coli Inhibition = 18.89 % DOI[10.6019/CHEMBL4296182]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Inhibition = 30.96 % DOI[10.6019/CHEMBL4296182]
NPT2 Others Unspecified n.a. Potency = 14125.4 nM PubChem BioAssay data set
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii Inhibition = 12.34 % DOI[10.6019/CHEMBL4296182]

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 NPC303581 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
0.9259 High Similarity NPC308267
0.875 High Similarity NPC67978
0.8182 Intermediate Similarity NPC153631
0.661 Remote Similarity NPC86469
0.5833 Remote Similarity NPC37144
0.5672 Remote Similarity NPC326205
0.5147 Remote Similarity NPC31311
0.5147 Remote Similarity NPC234392
0.5072 Remote Similarity NPC121400

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC303581 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