Natural Product: NPC47653

Natural Product IDNPC47653
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (R)-5-Ethyl-3-Hexadecanoyl-4-Methyl-5H-Furan-2-Oneo
IUPAC Name (2R)-4-hexadecanoyl-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one
Synonyms RK-682
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL426373
PubChem CID 54678922
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001983] Dihydrofurans
        • [CHEMONTID:0001982] Furanones
          • [CHEMONTID:0002223] Butenolides

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 KZTSLHQKWLYYAC-GOSISDBHSA-N
Standard InCHI InChI=1S/C21H36O5/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-17(23)19-20(24)18(16-22)26-21(19)25/h18,22,24H,2-16H2,1H3/t18-/m1/s1
SMILES CCCCCCCCCCCCCCCC(=O)C1=C(O)[C@H](OC1=O)CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.26 Volume:   399.257
?
Van der Waals volume.
Dense:   0.922 LogP:   5.626
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.728
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.533
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   16.0 Rigid Bonds:   7.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.233 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.042 Fsp3:   0.81
MCE-18:   16.421
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.345 Fluc inhibitor:   0.29
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.019
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.763 Promiscuous compounds:   0.399

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.14 MDCK Permeability:   -4.828
Pgp-inhibitor:   0.005 Pgp-substrate:   0.097
PAMPA:   0.011
?
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):   0.773
20% Bioavailability (F20%):   0.385 30% Bioavailability (F30%):   0.925
50% Bioavailability (F50%):   0.868

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.97
Plasma Protein Binding (PPB):   97.821% Volume Distribution (VD):   0.49
Fu: 2.386%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.559
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.863
BSEP inhibitor:   0.377

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.933
CYP2C19-inhibitor:   0.015 CYP2C19-substrate:   0.925
CYP2C9-inhibitor:   0.988 CYP2C9-substrate:   0.48
CYP2D6-inhibitor:   0.808 CYP2D6-substrate:   0.027
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   0.992
HLM stability:   0.032
?
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):  3.34 Half-life (T1/2):  1.282

ADMET: Toxicity

hERG Blockers:  0.046 hERG Blockers (10um):  0.252
Human Hepatotoxicity (H-HT):  0.521 Drug-induced Liver Injury (DILI):  0.421
AMES Toxicity:  0.165 Rat Oral Acute Toxicity:  0.081
Maximum Recommended Daily Dose:  0.033 Skin Sensitization:  1.0
Carcinogencity:  0.172 Eye Corrosion:  0.795
Eye Irritation:  0.986 Respiratory Toxicity:  0.279
Drug-induced Neurotoxicity:  0.015 Ototoxicity:  0.397
Hematotoxicity:  0.106 Drug-induced Nephrotoxicity:  0.643
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.06
A549 Cytotoxicity:  0.667 Hek293 Cytotoxicity:  0.058
BCF:   0.723
?
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:   4.45
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.123
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.384
?
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
NPO31296 Rhododendron brachycarpum Species Ericaceae Eukaryota n.a. leaf n.a. DOI[10.1007/BF02856638]
NPO30392 Morus Genus Sulidae Eukaryota root bark n.a. n.a. PMID[16356713]
NPO21023 Astilbe koreana Species Saxifragaceae Eukaryota n.a. n.a. n.a. PMID[16580200]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark n.a. n.a. PMID[17489632]
NPO15696 Polytrichastrum alpinum Species Polytrichaceae Eukaryota n.a. n.a. n.a. PMID[18053716]
NPO25373 Stereocaulon alpinum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. PMID[18288807]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. stem n.a. PMID[18484536]
NPO29554 Diospyros kaki Species Ebenaceae Eukaryota leaves n.a. n.a. PMID[18798681]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark Mukono, Uganda 2005-JUN PMID[19008110]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19836230]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20337486]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21116437]
NPO30392 Morus Genus Sulidae Eukaryota n.a. n.a. n.a. PMID[21319773]
NPO30392 Morus Genus Sulidae Eukaryota n.a. n.a. n.a. PMID[22297755]
NPO31296 Rhododendron brachycarpum Species Ericaceae Eukaryota n.a. n.a. n.a. PMID[22940448]
NPO40840 Eremophila spp. Species Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[26960032]
NPO25373 Stereocaulon alpinum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. PMID[29878768]
NPO40121 Eremophila oppositifolia subsp. Angustifolia Strain Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[32255628]
NPO29554 Diospyros kaki Species Ebenaceae Eukaryota Leaves n.a. n.a. PMID[3430165]
NPO21023 Astilbe koreana Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40840 Eremophila spp. Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25373 Stereocaulon alpinum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40121 Eremophila oppositifolia subsp. Angustifolia Strain Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29554 Diospyros kaki Species Ebenaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25373 Stereocaulon alpinum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21023 Astilbe koreana Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15696 Polytrichastrum alpinum Species Polytrichaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25373 Stereocaulon alpinum Species Stereocaulaceae 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
NPT1211 Individual protein Dual specificity protein phosphatase 3 Homo sapiens IC50 = 11600.0 nM PMID[11563920]
NPT3011 Individual protein Dual specificity phosphatase Cdc25B Mus musculus IC50 = 2200.0 nM PMID[11563920]
NPT1211 Individual protein Dual specificity protein phosphatase 3 Homo sapiens IC50 = 11700.0 nM PMID[11563920]
NPT3011 Individual protein Dual specificity phosphatase Cdc25B Mus musculus IC50 = 5100.0 nM PMID[11563920]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4500.0 nM PMID[25907369]
NPT1211 Individual protein Dual specificity protein phosphatase 3 Homo sapiens IC50 = 10200.0 nM PMID[16356713]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4.5 nM PMID[16545563]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 45000.0 nM PMID[17596944]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4100.0 nM PMID[18798681]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4700.0 nM PMID[19846295]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4400.0 nM PMID[20724155]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4000.0 nM PMID[22940448]
NPT1210 Individual protein T-cell protein-tyrosine phosphatase Homo sapiens IC50 = 5100.0 nM PMID[23387824]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 5620.0 nM PMID[23387824]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 99.1 % PMID[23387824]
NPT3012 Individual protein Heparanase Homo sapiens IC50 = 17000.0 nM PMID[23415087]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4600.0 nM PMID[24047800]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 4490.0 nM PMID[25819098]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 7300.0 nM PMID[32255628]
NPT3012 Individual protein Heparanase Homo sapiens IC50 = 17000.0 nM PMID[27240275]
NPT3012 Individual protein Heparanase Homo sapiens IC50 = 17000.0 nM PMID[37257254]
NPT3012 Individual protein Heparanase Homo sapiens IC50 = 17000.0 nM PMID[32222663]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 > 30000.0 nM PMID[19836230]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 30000.0 nM PMID[19836230]
NPT2 Others Unspecified n.a. IC50 > 100000.0 nM PMID[11563920]

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 NPC47653 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
0.5952 Remote Similarity NPC486719
0.5952 Remote Similarity NPC486718
0.5349 Remote Similarity NPC486713
0.5349 Remote Similarity NPC486714
0.5349 Remote Similarity NPC486715
0.5349 Remote Similarity NPC486710
0.5349 Remote Similarity NPC486711
0.5122 Remote Similarity NPC486712

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC47653 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