Natural Product: NPC26810

Natural Product IDNPC26810
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (5S,8R,13S,16R)-(-)-Pyrenophorol
IUPAC Name (3E,5S,8R,11E,13S,16R)-5,13-dihydroxy-8,16-dimethyl-1,9-dioxacyclohexadeca-3,11-diene-2,10-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2269362
PubChem CID 10935870
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues

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 RBQNDQOKFICJGL-UTBFYLPBSA-N
Standard InCHI InChI=1S/C16H24O6/c1-11-3-5-13(17)8-10-16(20)22-12(2)4-6-14(18)7-9-15(19)21-11/h7-14,17-18H,3-6H2,1-2H3/b9-7+,10-8+/t11-,12-,13+,14+/m1/s1
SMILES C[C@@H]1CC[C@@H](/C=C/C(=O)O[C@H](C)CC[C@@H](/C=C/C(=O)O1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.16 Volume:   318.931
?
Van der Waals volume.
Dense:   0.979 LogP:   0.787
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.179
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.913
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   93.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.654 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.695 Fsp3:   0.625
MCE-18:   23.538
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.43 Fluc inhibitor:   0.09
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.707 Promiscuous compounds:   0.656

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.857 MDCK Permeability:   -4.69
Pgp-inhibitor:   0.013 Pgp-substrate:   0.991
PAMPA:   0.996
?
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%):   0.58 30% Bioavailability (F30%):   0.867
50% Bioavailability (F50%):   0.89

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.535
Plasma Protein Binding (PPB):   61.602% Volume Distribution (VD):   -0.236
Fu: 38.626%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.561
OATP1B3 inhibitor:   0.732 BCRP inhibitor:   0.022
BSEP inhibitor:   0.81

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.342
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.238
?
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):  8.848 Half-life (T1/2):  1.919

ADMET: Toxicity

hERG Blockers:  0.016 hERG Blockers (10um):  0.051
Human Hepatotoxicity (H-HT):  0.999 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  0.998 Rat Oral Acute Toxicity:  0.402
Maximum Recommended Daily Dose:  1.0 Skin Sensitization:  1.0
Carcinogencity:  0.874 Eye Corrosion:  0.056
Eye Irritation:  0.972 Respiratory Toxicity:  0.998
Drug-induced Neurotoxicity:  1.0 Ototoxicity:  0.315
Hematotoxicity:  0.104 Drug-induced Nephrotoxicity:  1.0
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.954
A549 Cytotoxicity:  1.0 Hek293 Cytotoxicity:  0.933
BCF:   0.672
?
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:   3.229
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.601
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.203
?
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
NPO11443 Bistorta amplexicaulis Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[39741627]
NPO11443 Bistorta amplexicaulis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO14471 Streptomyces luridus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10103 Senecio iodanthus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13357 Vancouveria hexandra Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15629 Byssochlamys nivea Species Thermoascaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14986 Haplophyton crooksii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6109 Lonchocarpus subglaucescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18450 Oxytropis campestris Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18450 Oxytropis campestris Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4434 Bignonia hyacinthina Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8822 Alphonsea ventricosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9299.2 Hordeum vulgare subsp. vulgare Subspecies Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12507 Bixa orellana Species Bixaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5236 Polygonatum biflorum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13357 Vancouveria hexandra Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6109 Lonchocarpus subglaucescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18450 Oxytropis campestris Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10234 [brevibacterium] flavum Species Corynebacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO14365 Eysenhardtia subcoriacea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14471 Streptomyces luridus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO21402 Vespula vulgaris Species Vespidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15629 Byssochlamys nivea Species Thermoascaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10103 Senecio iodanthus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO390 Tectocoris diophthalmus Species Scutelleridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14068 Viburnum prunifolium Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9544 Eria angustifolia Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11443 Bistorta amplexicaulis Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14986 Haplophyton crooksii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12032 Oxylobus adscendens n.a. n.a. n.a. 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
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 32642.7 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT159 Individual protein Aberrant vpr protein Human immunodeficiency virus 1 Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 6309.6 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 15848.9 nM PubChem BioAssay data set
NPT9 Individual protein DNA polymerase eta Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 23280.9 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 10417.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency = 5804.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 14125.4 nM PubChem BioAssay data set

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 NPC26810 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
0.8485 Intermediate Similarity NPC19769
0.7879 Intermediate Similarity NPC96851
0.7647 Intermediate Similarity NPC608028
0.7568 Intermediate Similarity NPC122627
0.6842 Remote Similarity NPC484586
0.6757 Remote Similarity NPC607564
0.641 Remote Similarity NPC484590
0.641 Remote Similarity NPC484589
0.5946 Remote Similarity NPC263710
0.5897 Remote Similarity NPC606269
0.5676 Remote Similarity NPC97570
0.55 Remote Similarity NPC484593
0.55 Remote Similarity NPC484594
0.5238 Remote Similarity NPC475982
0.5128 Remote Similarity NPC61718
0.5122 Remote Similarity NPC481730
0.5116 Remote Similarity NPC484585
0.5116 Remote Similarity NPC201491

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC26810 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