Natural Product: NPC8659

Natural Product IDNPC8659
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QLFKXHHDGADCAX-VKLSVLLSSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11972373
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001766] Fatty acyl glycosides
          • [CHEMONTID:0003861] Fatty acyl glycosides of mono- and disaccharides

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 QLFKXHHDGADCAX-VKLSVLLSSA-N
Standard InCHI InChI=1S/C18H26O9/c1-23-11-7-6-10(16(24-2)17(11)25-3)5-4-8-26-18-15(22)14(21)13(20)12(9-19)27-18/h4-7,12-15,18-22H,8-9H2,1-3H3/b5-4+/t12-,13-,14+,15-,18-/m1/s1
SMILES COc1ccc(/C=C/CO[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)c(c1OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.16 Volume:   371.337
?
Van der Waals volume.
Dense:   1.04 LogP:   1.08
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.466
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.198
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   13.0
TPSA:   127.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.469 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.743 Fsp3:   0.556
MCE-18:   50.357
?
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:   0.38 Fluc inhibitor:   0.172
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.089
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.104
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.201 Promiscuous compounds:   0.098

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.344 MDCK Permeability:   -5.007
Pgp-inhibitor:   0.071 Pgp-substrate:   0.055
PAMPA:   0.28
?
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):   0.466
20% Bioavailability (F20%):   0.526 30% Bioavailability (F30%):   0.99
50% Bioavailability (F50%):   0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.039 MRP1:   0.023
Plasma Protein Binding (PPB):   70.642% Volume Distribution (VD):   -0.437
Fu: 29.513%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.487
BSEP inhibitor:   0.473

ADMET: Metabolism

CYP1A2-inhibitor:   0.032 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.602 CYP2C19-substrate:   0.025
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.298
CYP3A4-inhibitor:   0.684 CYP3A4-substrate:   0.02
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.982
HLM stability:   0.521
?
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):  3.175 Half-life (T1/2):  1.903

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.143
Human Hepatotoxicity (H-HT):  0.514 Drug-induced Liver Injury (DILI):  0.634
AMES Toxicity:  0.882 Rat Oral Acute Toxicity:  0.039
Maximum Recommended Daily Dose:  0.023 Skin Sensitization:  0.984
Carcinogencity:  0.418 Eye Corrosion:  0.0
Eye Irritation:  0.228 Respiratory Toxicity:  0.051
Drug-induced Neurotoxicity:  0.109 Ototoxicity:  0.901
Hematotoxicity:  0.425 Drug-induced Nephrotoxicity:  0.575
Genotoxicity:  0.044 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.266 Hek293 Cytotoxicity:  0.253
BCF:   0.551
?
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:   3.073
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.515
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.728
?
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
NPO19975 Pycnandra acuminata Species Sapotaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.phytochem.2007.07.001]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota seeds n.a. n.a. PMID[12762787]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12762809]
NPO6412 Echinacea pallida Species Asteraceae Eukaryota root n.a. n.a. PMID[15921428]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. leaf n.a. PMID[8699184]
NPO8129 Inocybe geophylla Species Inocybaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6412 Echinacea pallida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6856.1 Artemisia ludoviciana subsp. mexicana Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11339 Litsea salicifolia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12828 Dysidea tupha Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1695 Monascus pilosus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7874 Helichrysum lepidissimum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5534 Alternaria kikuchiana Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8609 Hopea utilis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10010 Evernia vulpina Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO633 Mesembryanthemum expansum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6856.1 Artemisia ludoviciana subsp. mexicana Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO633 Mesembryanthemum expansum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10010 Evernia vulpina Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10969 Epimedium sagittatum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO218 Acer carpinifolium Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11506 Stipa vaseyi Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26095 Hypericum revolutum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5534 Alternaria kikuchiana Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19975 Pycnandra acuminata Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1695 Monascus pilosus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5140 Dipteryx odorata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6412 Echinacea pallida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12118 Cleistopholis staudtii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11339 Litsea salicifolia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6861 Galium dasypodum Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12602 Leuzea centauroides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO940 Vernonia anisochaetoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12828 Dysidea tupha Species Dysideidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4759 Helleborus multifidus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10970 Osmorhiza aristata Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8129 Inocybe geophylla Species Inocybaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7874 Helichrysum lepidissimum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4322 Scabiosa succisa Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO633 Mesembryanthemum expansum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6856.1 Artemisia ludoviciana subsp. mexicana Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8609 Hopea utilis Species Dipterocarpaceae 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

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 NPC8659 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
0.619 Remote Similarity NPC470236
0.6066 Remote Similarity NPC132895
0.5965 Remote Similarity NPC306255
0.5938 Remote Similarity NPC307110
0.5667 Remote Similarity NPC313193
0.5333 Remote Similarity NPC270751
0.5325 Remote Similarity NPC470413
0.5303 Remote Similarity NPC302378
0.5185 Remote Similarity NPC269559
0.5161 Remote Similarity NPC610709
0.5156 Remote Similarity NPC162093
0.5125 Remote Similarity NPC302610

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC8659 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