Natural Product: NPC469910

Natural Product IDNPC469910
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cnicin
IUPAC Name n.a.
Synonyms Cnicin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1257707
PubChem CID n.a.
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
            • [CHEMONTID:0001771] Germacranolides 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 ZTDFZLVUIVPZDU-ZWSPDTATSA-N
Standard InCHI InChI=1S/C20H26O7/c1-11-5-4-6-14(9-21)8-17-18(13(3)20(25)27-17)16(7-11)26-19(24)12(2)15(23)10-22/h5,8,15-18,21-23H,2-4,6-7,9-10H2,1H3/b11-5-,14-8-/t15-,16+,17-,18-/m1/s1
SMILES C/C/1=C/CC/C(=C/[C@@H]2[C@H](C(=C)C(=O)O2)[C@H](C1)OC(=O)C(=C)[C@@H](CO)O)/CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   378.17 Volume:   383.076
?
Van der Waals volume.
Dense:   0.987 LogP:   1.21
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.401
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.238
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   113.29
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.371 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.056 Fsp3:   0.5
MCE-18:   38.4
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.246 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.161
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.076
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.502 Promiscuous compounds:   0.505

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.319 MDCK Permeability:   -4.921
Pgp-inhibitor:   0.004 Pgp-substrate:   0.756
PAMPA:   0.911
?
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):   0.276
20% Bioavailability (F20%):   0.58 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.3
Plasma Protein Binding (PPB):   76.219% Volume Distribution (VD):   -0.244
Fu: 23.673%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.884
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.018
BSEP inhibitor:   0.232

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.011 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.881
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.892
HLM stability:   0.156
?
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):  6.685 Half-life (T1/2):  1.323

ADMET: Toxicity

hERG Blockers:  0.001 hERG Blockers (10um):  0.012
Human Hepatotoxicity (H-HT):  0.839 Drug-induced Liver Injury (DILI):  0.914
AMES Toxicity:  0.859 Rat Oral Acute Toxicity:  0.115
Maximum Recommended Daily Dose:  0.556 Skin Sensitization:  1.0
Carcinogencity:  0.781 Eye Corrosion:  0.042
Eye Irritation:  0.801 Respiratory Toxicity:  0.044
Drug-induced Neurotoxicity:  0.276 Ototoxicity:  0.573
Hematotoxicity:  0.788 Drug-induced Nephrotoxicity:  0.978
Genotoxicity:  0.823 RPMI-8226 Immunitoxicity:  0.162
A549 Cytotoxicity:  0.376 Hek293 Cytotoxicity:  0.398
BCF:   0.587
?
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:   3.363
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.21
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.418
?
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
NPO40799 Bovine platelets Species n.a. n.a. n.a. n.a. n.a. PMID[1431933]
NPO21525 Centaurea spinosa Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[16180824]
NPO32860 cnicus benedictus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO3204 Centaurea malacitana Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[9358646]
NPO40799 Bovine platelets Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO21525 Centaurea spinosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3204 Centaurea malacitana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3204 Centaurea malacitana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21525 Centaurea spinosa 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
NPT2716 Individual protein UDP-N-acetylglucosamine 1-carboxyvinyltransferase Escherichia coli K-12 IC50 = 16700.0 nM PMID[20585132]
NPT2717 Individual protein UDP-N-acetylglucosamine 1-carboxyvinyltransferase Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228) IC50 = 10300.0 nM PMID[25066952]
NPT2717 Individual protein UDP-N-acetylglucosamine 1-carboxyvinyltransferase Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228) Inhibition = 64.0 % DrugMatrix in vivo data: Biochemistry
NPT840 Individual protein Transcriptional activator Myb Gallus gallus IC50 = 17906.06 nM PMID[20356735]
NPT840 Individual protein Transcriptional activator Myb Gallus gallus IC50 = 17920.0 nM PubChem BioAssay data set
NPT5373 Individual protein Methionine aminopeptidase 2 Homo sapiens Inhibition = 9.0 % PMID[15270577]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens GI50 = 37800.0 nM PMID[3509958]
NPT377 Cell line OVCAR-3 Homo sapiens GI50 = 37400.0 nM PMID[3509958]
NPT168 Cell line P388 Mus musculus IC50 = 6600.0 nM PMID[12662097]
NPT81 Cell line A549 Homo sapiens IC50 = 13200.0 nM PMID[15217270]
NPT139 Cell line HT-29 Homo sapiens IC50 = 13200.0 nM PMID[15217270]
NPT2309 Cell line CAPAN-1 Homo sapiens IC50 = 93000.0 nM PMID[20041704]
NPT2306 Cell line Ca-Ski Homo sapiens IC50 >= 100000.0 nM PMID[10425121]
NPT1938 Cell line Calu-6 Homo sapiens IC50 = 44000.0 nM PMID[22921744]
NPT2489 Cell line MeWo Homo sapiens IC50 >= 100000.0 nM PMID[24126094]
NPT762 Cell line A-431 Homo sapiens IC50 = 27000.0 nM PMID[16441084]
NPT941 Cell line HaCaT Homo sapiens IC50 = 80000.0 nM PMID[18809939]
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 5.0 ug.mL-1 PMID[15165157]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 3520.0 nM PMID[1431933]
NPT20967 Cell line Platelet n.a. IC50 = 3520.0 nM PMID[18271521]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 32.0 ug.mL-1 PMID[23493449]
NPT19 Organism Escherichia coli Escherichia coli MIC > 32.0 ug.mL-1 Open TG-GATES in vivo data: Hematology
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 32.0 ug.mL-1 PubChem BioAssay data set
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 1.25 ug.mL-1 PMID[17125222]
NPT2 Others Unspecified n.a. IC50 = 16700.0 nM PMID[20055477]
NPT2 Others Unspecified n.a. Inhibition = 97.0 % PMID[20100662]
NPT2 Others Unspecified n.a. IC50 = 20400.0 nM PMID[12822931]
NPT2 Others Unspecified n.a. IC50 = 10300.0 nM PMID[12822931]

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 NPC469910 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
0.8235 Intermediate Similarity NPC158756
0.8235 Intermediate Similarity NPC601035
0.7193 Intermediate Similarity NPC476803
0.7193 Intermediate Similarity NPC602701
0.7193 Intermediate Similarity NPC609128
0.7037 Intermediate Similarity NPC473390
0.6667 Remote Similarity NPC470755
0.6667 Remote Similarity NPC298801
0.6415 Remote Similarity NPC611318
0.6316 Remote Similarity NPC481909
0.6226 Remote Similarity NPC171204
0.6226 Remote Similarity NPC606745
0.6207 Remote Similarity NPC482126
0.6 Remote Similarity NPC24417
0.5965 Remote Similarity NPC116177
0.5862 Remote Similarity NPC477921
0.5862 Remote Similarity NPC600706
0.5846 Remote Similarity NPC474232
0.569 Remote Similarity NPC250940
0.569 Remote Similarity NPC169575
0.5667 Remote Similarity NPC482131
0.5645 Remote Similarity NPC486031
0.5593 Remote Similarity NPC602288
0.5574 Remote Similarity NPC482130
0.5574 Remote Similarity NPC482128
0.5574 Remote Similarity NPC482129
0.5556 Remote Similarity NPC476804
0.55 Remote Similarity NPC607796
0.55 Remote Similarity NPC608869
0.55 Remote Similarity NPC610116
0.5484 Remote Similarity NPC131669
0.5469 Remote Similarity NPC481911
0.5373 Remote Similarity NPC486033
0.5345 Remote Similarity NPC270126
0.5333 Remote Similarity NPC488296
0.5323 Remote Similarity NPC599997
0.5323 Remote Similarity NPC601440
0.5323 Remote Similarity NPC601519
0.5323 Remote Similarity NPC603351
0.5312 Remote Similarity NPC134725
0.5312 Remote Similarity NPC48657
0.5254 Remote Similarity NPC604968
0.5238 Remote Similarity NPC482127
0.5238 Remote Similarity NPC269509
0.52 Remote Similarity NPC605837
0.5167 Remote Similarity NPC7563
0.5161 Remote Similarity NPC320630
0.5156 Remote Similarity NPC477922
0.5147 Remote Similarity NPC475819
0.5085 Remote Similarity NPC476028

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC469910 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