Natural Product: NPC477454

Natural Product IDNPC477454
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GBKPEEONRMUYJY-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3590506
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003670] Aryl ketones
              • [CHEMONTID:0004296] Phenylketones
                • [CHEMONTID:0004298] Alkyl-phenylketones

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 GBKPEEONRMUYJY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H30O3/c1-3-4-5-6-7-8-9-10-11-12-16-13-17(21)14-18(22)19(16)15(2)20/h13-14,21-22H,3-12H2,1-2H3
SMILES CCCCCCCCCCCc1cc(O)cc(c1C(=O)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.22 Volume:   344.449
?
Van der Waals volume.
Dense:   0.889 LogP:   6.174
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.068
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.026
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   7.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.426 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.232 Fsp3:   0.632
MCE-18:   8.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.556 Fluc inhibitor:   0.032
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.136
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.76 Promiscuous compounds:   0.076

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.121 MDCK Permeability:   -4.757
Pgp-inhibitor:   0.272 Pgp-substrate:   0.087
PAMPA:   0.004
?
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):   0.285
20% Bioavailability (F20%):   0.881 30% Bioavailability (F30%):   0.983
50% Bioavailability (F50%):   0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.082 MRP1:   0.919
Plasma Protein Binding (PPB):   99.305% Volume Distribution (VD):   1.16
Fu: 0.874%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.825
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.937
BSEP inhibitor:   0.858

ADMET: Metabolism

CYP1A2-inhibitor:   0.977 CYP1A2-substrate:   0.987
CYP2C19-inhibitor:   0.4 CYP2C19-substrate:   0.542
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.891
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.988
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.785 CYP2C8-inhibitor:   1.0
HLM stability:   0.339
?
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):  2.951 Half-life (T1/2):  1.214

ADMET: Toxicity

hERG Blockers:  0.37 hERG Blockers (10um):  0.813
Human Hepatotoxicity (H-HT):  0.552 Drug-induced Liver Injury (DILI):  0.28
AMES Toxicity:  0.211 Rat Oral Acute Toxicity:  0.191
Maximum Recommended Daily Dose:  0.445 Skin Sensitization:  0.965
Carcinogencity:  0.289 Eye Corrosion:  0.678
Eye Irritation:  0.996 Respiratory Toxicity:  0.951
Drug-induced Neurotoxicity:  0.096 Ototoxicity:  0.207
Hematotoxicity:  0.2 Drug-induced Nephrotoxicity:  0.194
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.097
A549 Cytotoxicity:  0.839 Hek293 Cytotoxicity:  0.551
BCF:   1.539
?
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:   5.108
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.025
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.929
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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
NPO11898 Lobophora variegata Species Dictyotaceae Eukaryota n.a. at depths of 630 m at El Mdano (Tenerife, Canary Islands) n.a. PMID[26126835]
NPO40175 Knema hookeriana Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[27008174]
NPO11898 Lobophora variegata Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40175 Knema hookeriana Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11898 Lobophora variegata Species Dictyotaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1204 Organism Enterococcus faecalis ATCC 29212 Enterococcus faecalis ATCC 29212 Inhibition = -9.8 % PMID[26126835]
NPT21617 Protein-protein interaction Induced myeloid leukemia cell differentiation protein Mcl-1/BH3-interacting domain death agonist Homo sapiens Ki > 33000.0 nM PMID[27008174]
NPT19 Organism Escherichia coli Escherichia coli Inhibition = -1.0 % PMID[26126835]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus Inhibition = 17.0 % PMID[26126835]
NPT21616 Protein-protein interaction Bcl-xL/BAK Homo sapiens Ki > 23000.0 nM PMID[27008174]

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 NPC477454 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 NPC473691
0.8293 Intermediate Similarity NPC483450
0.8049 Intermediate Similarity NPC483449
0.7674 Intermediate Similarity NPC259942
0.7674 Intermediate Similarity NPC92624
0.6279 Remote Similarity NPC477453
0.56 Remote Similarity NPC70380
0.55 Remote Similarity NPC294186
0.55 Remote Similarity NPC147310
0.55 Remote Similarity NPC137415
0.55 Remote Similarity NPC166313
0.55 Remote Similarity NPC192032
0.55 Remote Similarity NPC24407
0.55 Remote Similarity NPC11280
0.5455 Remote Similarity NPC164870
0.5192 Remote Similarity NPC605699
0.5167 Remote Similarity NPC486904
0.5088 Remote Similarity NPC29577

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477454 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