Natural Product: NPC26353

Natural Product IDNPC26353
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DJIVYOZJUUNZBB-WDNDVIMCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3084562
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001248] Hydroxybenzoic acid derivatives
            • [CHEMONTID:0001251] Gallic acid 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 DJIVYOZJUUNZBB-WDNDVIMCSA-N
Standard InCHI InChI=1S/C18H25NO5/c1-19-12-5-6-13(19)10-14(9-12)24-18(20)11-7-15(21-2)17(23-4)16(8-11)22-3/h7-8,12-14H,5-6,9-10H2,1-4H3/t12-,13+,14+
SMILES CN1[C@H]2CC[C@@H]1C[C@@H](C2)OC(=O)c1cc(c(c(c1)OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   335.17 Volume:   338.617
?
Van der Waals volume.
Dense:   0.99 LogP:   1.929
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.042
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.276
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   57.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.771 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.824 Fsp3:   0.611
MCE-18:   62.69
?
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:   0.171 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.051
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.05
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.009 Promiscuous compounds:   0.746

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.919 MDCK Permeability:   -4.777
Pgp-inhibitor:   0.059 Pgp-substrate:   0.818
PAMPA:   0.036
?
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%):   0.002 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.042

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.994 MRP1:   0.868
Plasma Protein Binding (PPB):   75.277% Volume Distribution (VD):   0.415
Fu: 26.085%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.221
OATP1B3 inhibitor:   0.095 BCRP inhibitor:   0.223
BSEP inhibitor:   0.42

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.252
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.325
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.655
?
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):  8.085 Half-life (T1/2):  1.335

ADMET: Toxicity

hERG Blockers:  0.325 hERG Blockers (10um):  0.695
Human Hepatotoxicity (H-HT):  0.554 Drug-induced Liver Injury (DILI):  0.41
AMES Toxicity:  0.452 Rat Oral Acute Toxicity:  0.405
Maximum Recommended Daily Dose:  0.715 Skin Sensitization:  0.728
Carcinogencity:  0.68 Eye Corrosion:  0.109
Eye Irritation:  0.427 Respiratory Toxicity:  0.811
Drug-induced Neurotoxicity:  0.887 Ototoxicity:  0.495
Hematotoxicity:  0.227 Drug-induced Nephrotoxicity:  0.826
Genotoxicity:  0.087 RPMI-8226 Immunitoxicity:  0.149
A549 Cytotoxicity:  0.227 Hek293 Cytotoxicity:  0.276
BCF:   0.876
?
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:   3.655
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.808
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.277
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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
NPO33258 erythroxylum pervillei Species Erythroxylaceae Eukaryota n.a. n.a. n.a. PMID[11754602]

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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1034 Cell line Lu1 Homo sapiens ED50 > 20.0 ug ml-1 PMID[25819096]
NPT1851 Cell line Col2 Homo sapiens ED50 > 20.0 ug ml-1 PMID[19124664]
NPT91 Cell line KB Homo sapiens ED50 > 20.0 ug ml-1 DOI[10.6019/CHEMBL1201861]
NPT858 Cell line LNCaP Homo sapiens ED50 > 20.0 ug ml-1 Open TG-GATES in vivo data: Organ Weight
NPT2345 Cell line SW626 Homo sapiens ED50 > 20.0 ug ml-1 PMID[24223237]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 > 20.0 ug ml-1 PMID[11754602]

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 NPC26353 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
0.6415 Remote Similarity NPC605931
0.6304 Remote Similarity NPC26285
0.6304 Remote Similarity NPC609506
0.6066 Remote Similarity NPC329992
0.5224 Remote Similarity NPC473562

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC26353 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
0.58 Remote Similarity NPD1654 Clinical (unspecified phase)

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