Natural Product: NPC289004

Natural Product IDNPC289004
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CNIULSUYTFOEHN-OEHPVWETSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1544783
PubChem CID 16745514
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001543] Sesquiterpene lactones

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 CNIULSUYTFOEHN-OEHPVWETSA-N
Standard InCHI InChI=1S/C17H22O5/c1-8-7-10-12-13(15(2)9(8)5-6-11(15)18)22-17(4,20)16(12,3)14(19)21-10/h5-6,8-10,12-13,20H,7H2,1-4H3/t8-,9-,10+,12-,13-,15+,16+,17?/m1/s1
SMILES C[C@@H]1C[C@H]2[C@@H]3[C@H]([C@@]4(C)[C@@H]1C=CC4=O)OC(C)([C@]3(C)C(=O)O2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.15 Volume:   304.404
?
Van der Waals volume.
Dense:   1.006 LogP:   1.462
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.77
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.998
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   72.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.686 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.228 Fsp3:   0.765
MCE-18:   72.8
?
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:   0.275 Fluc inhibitor:   0.043
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.412 Promiscuous compounds:   0.648

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.925 MDCK Permeability:   -4.626
Pgp-inhibitor:   0.464 Pgp-substrate:   0.036
PAMPA:   0.776
?
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):   0.006
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.071
50% Bioavailability (F50%):   0.711

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.919 MRP1:   0.847
Plasma Protein Binding (PPB):   74.663% Volume Distribution (VD):   -0.107
Fu: 25.042%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.017
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.679 CYP1A2-substrate:   0.637
CYP2C19-inhibitor:   0.981 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.91
?
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):  8.168 Half-life (T1/2):  1.904

ADMET: Toxicity

hERG Blockers:  0.05 hERG Blockers (10um):  0.395
Human Hepatotoxicity (H-HT):  0.539 Drug-induced Liver Injury (DILI):  0.484
AMES Toxicity:  0.78 Rat Oral Acute Toxicity:  0.7
Maximum Recommended Daily Dose:  0.639 Skin Sensitization:  0.977
Carcinogencity:  0.959 Eye Corrosion:  0.451
Eye Irritation:  0.899 Respiratory Toxicity:  0.631
Drug-induced Neurotoxicity:  0.582 Ototoxicity:  0.217
Hematotoxicity:  0.142 Drug-induced Nephrotoxicity:  0.673
Genotoxicity:  0.834 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.09 Hek293 Cytotoxicity:  0.338
BCF:   0.52
?
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:   3.09
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.418
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.913
?
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
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota roots n.a. n.a. PMID[16989524]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. rhizome n.a. PMID[22863942]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota aerial parts n.a. n.a. PMID[24042007]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. PMID[38838926]
NPO21806 Helenium tenuifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18919 Helenium amarum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16706 Helenium puberulum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16598 Helenium elegans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16706 Helenium puberulum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18919 Helenium amarum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21806 Helenium tenuifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16598 Helenium elegans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16598 Helenium elegans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16706 Helenium puberulum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21806 Helenium tenuifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18919 Helenium amarum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18919 Helenium amarum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16598 Helenium elegans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21806 Helenium tenuifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16706 Helenium puberulum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21806 Helenium tenuifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16706 Helenium puberulum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16598 Helenium elegans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26233 Helenium autumnale Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18919 Helenium amarum Species Asteraceae 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
NPT3 Individual protein Thioredoxin glutathione reductase Schistosoma mansoni Potency = 44668.4 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 16360.1 nM PubChem BioAssay data set
NPT1474 Individual protein ATP-dependent Clp protease proteolytic subunit Bacillus subtilis (strain 168) Potency n.a. 7079.5 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 32642.7 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT524 Individual protein Serine-protein kinase ATM Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 21331.3 nM PubChem BioAssay data set
NPT59 Individual protein DNA polymerase beta Homo sapiens Potency = 89125.1 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 50118.7 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
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 19952.6 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 11689.1 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 13115.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 17782.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 3162.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 22387.2 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 NPC289004 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
0.5385 Remote Similarity NPC70555
0.5385 Remote Similarity NPC104961
0.5263 Remote Similarity NPC141191
0.5185 Remote Similarity NPC123177
0.5185 Remote Similarity NPC70595
0.5185 Remote Similarity NPC150978
0.5172 Remote Similarity NPC169205
0.5091 Remote Similarity NPC70422
0.5091 Remote Similarity NPC610675
0.5085 Remote Similarity NPC185553

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC289004 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