Natural Product: NPC238530

Natural Product IDNPC238530
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PQECCKIOFCWGRJ-HNNXBMFYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2314732
PubChem CID 12313091
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001909] Protoberberine alkaloids and derivatives

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 PQECCKIOFCWGRJ-HNNXBMFYSA-N
Standard InCHI InChI=1S/C19H19NO4/c1-22-16-3-2-11-6-15-13-8-18-17(23-10-24-18)7-12(13)4-5-20(15)9-14(11)19(16)21/h2-3,7-8,15,21H,4-6,9-10H2,1H3/t15-/m0/s1
SMILES COc1ccc2c(c1O)CN1[C@@H](C2)c2cc3OCOc3cc2CC1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   325.13 Volume:   324.737
?
Van der Waals volume.
Dense:   1.001 LogP:   1.685
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.695
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.696
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   25.0
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:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.045 Fsp3:   0.368
MCE-18:   86.538
?
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:   1
Colloidal aggregators:   0.427 Fluc inhibitor:   0.236
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.579
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.379
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.085

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.911 MDCK Permeability:   -4.693
Pgp-inhibitor:   0.157 Pgp-substrate:   0.339
PAMPA:   0.01
?
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):   0.001
20% Bioavailability (F20%):   0.21 30% Bioavailability (F30%):   0.014
50% Bioavailability (F50%):   0.873

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.953 MRP1:   0.968
Plasma Protein Binding (PPB):   91.84% Volume Distribution (VD):   -0.241
Fu: 7.402%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.671
OATP1B3 inhibitor:   0.562 BCRP inhibitor:   0.241
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.477
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.934
CYP3A4-inhibitor:   0.987 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   0.009
HLM stability:   0.967
?
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):  6.364 Half-life (T1/2):  1.945

ADMET: Toxicity

hERG Blockers:  0.424 hERG Blockers (10um):  0.597
Human Hepatotoxicity (H-HT):  0.581 Drug-induced Liver Injury (DILI):  0.312
AMES Toxicity:  0.613 Rat Oral Acute Toxicity:  0.733
Maximum Recommended Daily Dose:  0.815 Skin Sensitization:  0.642
Carcinogencity:  0.859 Eye Corrosion:  0.003
Eye Irritation:  0.437 Respiratory Toxicity:  0.949
Drug-induced Neurotoxicity:  0.75 Ototoxicity:  0.375
Hematotoxicity:  0.305 Drug-induced Nephrotoxicity:  0.612
Genotoxicity:  0.897 RPMI-8226 Immunitoxicity:  0.113
A549 Cytotoxicity:  0.297 Hek293 Cytotoxicity:  0.407
BCF:   1.624
?
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:   4.031
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.396
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.81
?
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
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)98060-9]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. Oakham, MA, US n.a. PMID[16562853]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[17250743]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[21094631]
NPO4986 Eschscholzia californica 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]
NPO4986 Eschscholzia californica 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]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3504 Argemone mexicana Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3504 Argemone mexicana 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
NPT243 Individual protein Dopamine D2 receptor Homo sapiens Ki > 5000.0 nM PMID[23332346]
NPT242 Individual protein Dopamine D1 receptor Homo sapiens Ki = 60.0 nM PMID[23332346]
NPT242 Individual protein Dopamine D1 receptor Homo sapiens Inhibition = 98.7 % PMID[23332346]
NPT243 Individual protein Dopamine D2 receptor Homo sapiens Inhibition = 78.0 % PMID[23332346]
NPT290 Individual protein Serotonin 2a (5-HT2a) receptor Homo sapiens Inhibition = 49.1 % PMID[23332346]
NPT677 Individual protein Coagulation factor III Homo sapiens IC50 = 36.41 nM PMID[23199480]
NPT92 Individual protein Serotonin 1a (5-HT1a) receptor Homo sapiens Ki > 5000.0 nM PMID[23332346]
NPT92 Individual protein Serotonin 1a (5-HT1a) receptor Homo sapiens Inhibition = 82.8 % PMID[23332346]

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 NPC238530 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 NPC276944
0.875 High Similarity NPC276588
0.875 High Similarity NPC127674
0.875 High Similarity NPC278799
0.7377 Intermediate Similarity NPC249797
0.7377 Intermediate Similarity NPC193949
0.6825 Remote Similarity NPC216459
0.6825 Remote Similarity NPC41178
0.6825 Remote Similarity NPC138487
0.6769 Remote Similarity NPC606650
0.6667 Remote Similarity NPC469817
0.6462 Remote Similarity NPC326205
0.6406 Remote Similarity NPC31311
0.6406 Remote Similarity NPC234392
0.6143 Remote Similarity NPC232514
0.6 Remote Similarity NPC90820
0.5781 Remote Similarity NPC210437
0.5781 Remote Similarity NPC16107
0.5781 Remote Similarity NPC106295
0.5758 Remote Similarity NPC39701
0.5758 Remote Similarity NPC184026
0.5692 Remote Similarity NPC51957
0.5574 Remote Similarity NPC128019
0.5507 Remote Similarity NPC204828
0.5507 Remote Similarity NPC295691
0.5507 Remote Similarity NPC207757
0.5507 Remote Similarity NPC54379
0.5507 Remote Similarity NPC5238
0.5373 Remote Similarity NPC151895
0.5362 Remote Similarity NPC27887
0.5211 Remote Similarity NPC264850
0.5152 Remote Similarity NPC111485
0.5152 Remote Similarity NPC88249
0.5152 Remote Similarity NPC220858
0.5139 Remote Similarity NPC2314

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC238530 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
0.5781 Remote Similarity NPD4584 Phase 2

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