Natural Product: NPC482128

Natural Product IDNPC482128
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OEDXUXSUBLVBSY-IMFDDDINSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102364361
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 OEDXUXSUBLVBSY-IMFDDDINSA-N
Standard InCHI InChI=1S/C22H28O7/c1-6-16(11-23)22(26)29-18-9-12(2)7-8-17(27-15(5)24)13(3)10-19-20(18)14(4)21(25)28-19/h6-7,10,17-20,23H,4,8-9,11H2,1-3,5H3/b12-7+,13-10-,16-6-/t17-,18+,19+,20+/m0/s1
SMILES C/C=C(/CO)C(=O)O[C@@H]1C/C(=C/C[C@@H](/C(=C[C@@H]2[C@@H]1C(=C)C(=O)O2)/C)OC(=O)C)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   404.18 Volume:   415.032
?
Van der Waals volume.
Dense:   0.974 LogP:   1.802
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.123
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.111
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   99.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.333 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.007 Fsp3:   0.5
MCE-18:   40.182
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.358 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.02
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.612 Promiscuous compounds:   0.378

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.865 MDCK Permeability:   -4.698
Pgp-inhibitor:   0.979 Pgp-substrate:   0.456
PAMPA:   0.117
?
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):   0.277
20% Bioavailability (F20%):   0.836 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.967
Plasma Protein Binding (PPB):   80.939% Volume Distribution (VD):   -0.153
Fu: 17.402%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.022
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.041 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.284 CYP3A4-substrate:   0.783
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.255
?
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):  7.784 Half-life (T1/2):  0.68

ADMET: Toxicity

hERG Blockers:  0.003 hERG Blockers (10um):  0.045
Human Hepatotoxicity (H-HT):  0.798 Drug-induced Liver Injury (DILI):  0.977
AMES Toxicity:  0.831 Rat Oral Acute Toxicity:  0.177
Maximum Recommended Daily Dose:  0.426 Skin Sensitization:  0.999
Carcinogencity:  0.886 Eye Corrosion:  0.153
Eye Irritation:  0.855 Respiratory Toxicity:  0.088
Drug-induced Neurotoxicity:  0.198 Ototoxicity:  0.334
Hematotoxicity:  0.65 Drug-induced Nephrotoxicity:  0.881
Genotoxicity:  0.846 RPMI-8226 Immunitoxicity:  0.094
A549 Cytotoxicity:  0.276 Hek293 Cytotoxicity:  0.23
BCF:   0.588
?
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:   3.401
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.367
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.604
?
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
NPO24212 Eupatorium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[15104494]
NPO24212 Eupatorium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[19318257]
NPO24212 Eupatorium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[29280632]
NPO24212 Eupatorium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24212 Eupatorium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24212 Eupatorium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24212 Eupatorium chinense 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens IC50 = 3600.0 nM PMID[29280632]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 800.0 nM PMID[29280632]
NPT2306 Cell line Ca-Ski Homo sapiens IC50 > 10000.0 nM PMID[29280632]
NPT25746 Cell line CNE-2 Homo sapiens IC50 > 10000.0 nM PMID[29280632]

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 NPC482128 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
1.0 High Similarity NPC482129
0.902 High Similarity NPC134725
0.902 High Similarity NPC48657
0.8431 Intermediate Similarity NPC482130
0.8333 Intermediate Similarity NPC476028
0.8269 Intermediate Similarity NPC269509
0.7586 Intermediate Similarity NPC486033
0.7547 Intermediate Similarity NPC482126
0.7547 Intermediate Similarity NPC482131
0.7544 Intermediate Similarity NPC486037
0.7241 Intermediate Similarity NPC486034
0.7222 Intermediate Similarity NPC266957
0.7143 Intermediate Similarity NPC482133
0.6964 Remote Similarity NPC482127
0.6667 Remote Similarity NPC482132
0.6441 Remote Similarity NPC230800
0.6271 Remote Similarity NPC482134
0.625 Remote Similarity NPC59330
0.6207 Remote Similarity NPC470755
0.6207 Remote Similarity NPC298801
0.6 Remote Similarity NPC486031
0.5873 Remote Similarity NPC96018
0.5862 Remote Similarity NPC158756
0.5862 Remote Similarity NPC601035
0.5846 Remote Similarity NPC486035
0.569 Remote Similarity NPC473321
0.5636 Remote Similarity NPC603669
0.5574 Remote Similarity NPC469910
0.5517 Remote Similarity NPC250940
0.5517 Remote Similarity NPC169575
0.5455 Remote Similarity NPC171204
0.5455 Remote Similarity NPC606745
0.5397 Remote Similarity NPC488118
0.5357 Remote Similarity NPC611318
0.5333 Remote Similarity NPC481909
0.5323 Remote Similarity NPC471141
0.5286 Remote Similarity NPC486032
0.5278 Remote Similarity NPC486036
0.5273 Remote Similarity NPC97516
0.5238 Remote Similarity NPC488120
0.5217 Remote Similarity NPC486030
0.5172 Remote Similarity NPC270126
0.5167 Remote Similarity NPC488296
0.5156 Remote Similarity NPC475748
0.5077 Remote Similarity NPC481911

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482128 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