Natural Product: NPC298008

Natural Product IDNPC298008
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JWXKBCGJLCEZTJ-ZDUSSCGKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14395308
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 JWXKBCGJLCEZTJ-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C19H19NO4/c1-21-16-6-10-3-4-20-13-5-11-7-14-15(24-9-23-14)8-12(11)18(17(10)13)19(16)22-2/h6-8,13,20H,3-5,9H2,1-2H3/t13-/m0/s1
SMILES COc1cc2CCN[C@H]3Cc4cc5c(cc4-c(c23)c1OC)OCO5

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   325.13 Volume:   324.737
?
Van der Waals volume.
Dense:   1.001 LogP:   2.242
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.47
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.262
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   24.0
TPSA:   48.95
?
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:   0.92 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.159 Fsp3:   0.368
MCE-18:   84.615
?
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:   0.625 Fluc inhibitor:   0.299
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.689
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.22
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.569

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.999 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.042 Pgp-substrate:   0.832
PAMPA:   0.09
?
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):   0.006
20% Bioavailability (F20%):   0.296 30% Bioavailability (F30%):   0.041
50% Bioavailability (F50%):   0.8

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.315 MRP1:   0.933
Plasma Protein Binding (PPB):   75.678% Volume Distribution (VD):   0.387
Fu: 25.604%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.7
OATP1B3 inhibitor:   0.853 BCRP inhibitor:   0.093
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.077
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.935 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.982
CYP3A4-inhibitor:   0.898 CYP3A4-substrate:   0.985
CYP2B6-substrate:   0.975 CYP2C8-inhibitor:   0.0
HLM stability:   0.093
?
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):  5.876 Half-life (T1/2):  1.919

ADMET: Toxicity

hERG Blockers:  0.531 hERG Blockers (10um):  0.698
Human Hepatotoxicity (H-HT):  0.683 Drug-induced Liver Injury (DILI):  0.399
AMES Toxicity:  0.819 Rat Oral Acute Toxicity:  0.825
Maximum Recommended Daily Dose:  0.928 Skin Sensitization:  0.639
Carcinogencity:  0.705 Eye Corrosion:  0.001
Eye Irritation:  0.195 Respiratory Toxicity:  0.974
Drug-induced Neurotoxicity:  0.927 Ototoxicity:  0.408
Hematotoxicity:  0.247 Drug-induced Nephrotoxicity:  0.661
Genotoxicity:  0.886 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.394 Hek293 Cytotoxicity:  0.335
BCF:   1.944
?
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:   3.995
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.921
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.825
?
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
NPO40486 Cryptocarya densiflora BI. Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[27492195]
NPO40696 Cryptocarya infectoria Miq. Strain Lauraceae Eukaryota n.a. n.a. n.a. PMID[27492195]

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
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = 75.81 % PMID[27492195]
NPT67 Individual protein Cholinesterase Equus caballus IC50 = 94450.0 nM PMID[27492195]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = 50.38 % PMID[27492195]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus IC50 = 205550.0 nM PMID[27492195]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ratio IC50 = 0.46 n.a. PMID[27492195]
NPT2 Others Unspecified n.a. Ratio IC50 = 2.18 n.a. PMID[27492195]

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 NPC298008 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
0.8519 High Similarity NPC6152
0.6935 Remote Similarity NPC155442
0.6935 Remote Similarity NPC312918
0.678 Remote Similarity NPC69712
0.678 Remote Similarity NPC220228
0.6557 Remote Similarity NPC470879
0.6552 Remote Similarity NPC203784
0.6552 Remote Similarity NPC170503
0.6552 Remote Similarity NPC126519
0.6393 Remote Similarity NPC189470
0.6393 Remote Similarity NPC191213
0.6129 Remote Similarity NPC302713
0.6102 Remote Similarity NPC204947
0.6094 Remote Similarity NPC152212
0.6094 Remote Similarity NPC28341
0.6 Remote Similarity NPC600341
0.5909 Remote Similarity NPC57036
0.5909 Remote Similarity NPC600117
0.5821 Remote Similarity NPC135772
0.5625 Remote Similarity NPC192135
0.5606 Remote Similarity NPC481950
0.5556 Remote Similarity NPC610238

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC298008 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