Natural Product: NPC172158

Natural Product IDNPC172158
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XHMYANYRIDZIHX-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins 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 XHMYANYRIDZIHX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O6/c1-12(2)4-9-15-16(22)10-17(23)20-18(24)11-19(27-21(15)20)26-14-7-5-13(25-3)6-8-14/h4-8,10-11,22-23H,9H2,1-3H3
SMILES CC(=CCc1c(cc(c2c(=O)cc(Oc3ccc(cc3)OC)oc12)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.13 Volume:   375.116
?
Van der Waals volume.
Dense:   0.981 LogP:   4.075
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.402
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.867
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.644 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.766 Fsp3:   0.19
MCE-18:   19.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.729 Fluc inhibitor:   0.419
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.939
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.763
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.244 Promiscuous compounds:   0.189

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.933 MDCK Permeability:   -4.665
Pgp-inhibitor:   0.336 Pgp-substrate:   0.146
PAMPA:   0.293
?
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):   0.136
20% Bioavailability (F20%):   0.841 30% Bioavailability (F30%):   0.967
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.875
Plasma Protein Binding (PPB):   96.248% Volume Distribution (VD):   0.182
Fu: 3.0%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.973 BCRP inhibitor:   0.879
BSEP inhibitor:   0.838

ADMET: Metabolism

CYP1A2-inhibitor:   0.937 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.971 CYP2C9-substrate:   0.075
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.982
CYP3A4-inhibitor:   0.019 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  3.961 Half-life (T1/2):  1.124

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.6
Human Hepatotoxicity (H-HT):  0.573 Drug-induced Liver Injury (DILI):  0.969
AMES Toxicity:  0.804 Rat Oral Acute Toxicity:  0.603
Maximum Recommended Daily Dose:  0.789 Skin Sensitization:  0.72
Carcinogencity:  0.664 Eye Corrosion:  0.001
Eye Irritation:  0.9 Respiratory Toxicity:  0.969
Drug-induced Neurotoxicity:  0.152 Ototoxicity:  0.188
Hematotoxicity:  0.145 Drug-induced Nephrotoxicity:  0.221
Genotoxicity:  0.92 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.475 Hek293 Cytotoxicity:  0.766
BCF:   1.837
?
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:   4.625
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.057
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.467
?
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]
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]
NPO6856.1 Artemisia ludoviciana subsp. mexicana Subspecies Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10010 Evernia vulpina Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11339 Litsea salicifolia Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8609 Hopea utilis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5534 Alternaria kikuchiana Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7874 Helichrysum lepidissimum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1695 Monascus pilosus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12828 Dysidea tupha Species Dysideidae 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]
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]
NPO20569 Psychotria serpens Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10010 Evernia vulpina Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12602 Leuzea centauroides Species Asteraceae 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]
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 NPC172158 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
0.8095 Intermediate Similarity NPC482019
0.7538 Intermediate Similarity NPC482024
0.7353 Intermediate Similarity NPC482023
0.6338 Remote Similarity NPC471981
0.6338 Remote Similarity NPC482020
0.6111 Remote Similarity NPC482021
0.5556 Remote Similarity NPC273538
0.5072 Remote Similarity NPC482938

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC172158 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
0.5556 Remote Similarity NPD4378 Phase 3

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