Natural Product: NPC482126

Natural Product IDNPC482126
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JINQTWSVNPNCHU-QMGPOFJLSA-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]

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 JINQTWSVNPNCHU-QMGPOFJLSA-N
Standard InCHI InChI=1S/C22H28O8/c1-6-15(10-23)22(27)30-17-8-11(2)7-16(25)20(28-14(5)24)12(3)9-18-19(17)13(4)21(26)29-18/h6-7,9,16-20,23,25H,4,8,10H2,1-3,5H3/b11-7+,12-9-,15-6-/t16-,17-,18-,19-,20-/m1/s1
SMILES C/C=C(/CO)C(=O)O[C@@H]1C/C(=C/[C@H]([C@@H](/C(=C[C@@H]2[C@@H]1C(=C)C(=O)O2)/C)OC(=O)C)O)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   420.18 Volume:   423.822
?
Van der Waals volume.
Dense:   0.991 LogP:   0.814
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.184
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.416
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   119.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.304 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.221 Fsp3:   0.5
MCE-18:   42.545
?
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:   0.732 Fluc inhibitor:   0.006
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.065
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.01
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.543 Promiscuous compounds:   0.412

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.092 MDCK Permeability:   -4.775
Pgp-inhibitor:   0.769 Pgp-substrate:   0.341
PAMPA:   0.42
?
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):   0.609
20% Bioavailability (F20%):   0.695 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.926
Plasma Protein Binding (PPB):   65.773% Volume Distribution (VD):   -0.131
Fu: 31.953%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.005
BSEP inhibitor:   0.943

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.014
CYP2C9-inhibitor:   0.704 CYP2C9-substrate:   0.042
CYP2D6-inhibitor:   0.04 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.134 CYP3A4-substrate:   0.862
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.99
HLM stability:   0.058
?
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):  7.901 Half-life (T1/2):  0.864

ADMET: Toxicity

hERG Blockers:  0.003 hERG Blockers (10um):  0.068
Human Hepatotoxicity (H-HT):  0.855 Drug-induced Liver Injury (DILI):  0.981
AMES Toxicity:  0.825 Rat Oral Acute Toxicity:  0.159
Maximum Recommended Daily Dose:  0.162 Skin Sensitization:  0.999
Carcinogencity:  0.736 Eye Corrosion:  0.01
Eye Irritation:  0.66 Respiratory Toxicity:  0.029
Drug-induced Neurotoxicity:  0.154 Ototoxicity:  0.541
Hematotoxicity:  0.734 Drug-induced Nephrotoxicity:  0.921
Genotoxicity:  0.977 RPMI-8226 Immunitoxicity:  0.167
A549 Cytotoxicity:  0.295 Hek293 Cytotoxicity:  0.158
BCF:   0.534
?
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:   3.305
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.145
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.387
?
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
NPT2306 Cell line Ca-Ski Homo sapiens IC50 > 10000.0 nM PMID[29280632]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 10000.0 nM PMID[29280632]
NPT65 Cell line HepG2 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 NPC482126 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
0.7547 Intermediate Similarity NPC482128
0.7547 Intermediate Similarity NPC482129
0.7143 Intermediate Similarity NPC134725
0.7143 Intermediate Similarity NPC48657
0.7091 Intermediate Similarity NPC482127
0.6909 Remote Similarity NPC482130
0.6833 Remote Similarity NPC486033
0.6667 Remote Similarity NPC482133
0.6379 Remote Similarity NPC486031
0.6316 Remote Similarity NPC470755
0.6316 Remote Similarity NPC298801
0.623 Remote Similarity NPC486037
0.6207 Remote Similarity NPC469910
0.6207 Remote Similarity NPC269509
0.614 Remote Similarity NPC482131
0.6111 Remote Similarity NPC476028
0.6102 Remote Similarity NPC482134
0.6 Remote Similarity NPC230800
0.5965 Remote Similarity NPC158756
0.5965 Remote Similarity NPC601035
0.5714 Remote Similarity NPC96018
0.5614 Remote Similarity NPC250940
0.5614 Remote Similarity NPC169575
0.5606 Remote Similarity NPC59330
0.5469 Remote Similarity NPC486034
0.5469 Remote Similarity NPC482132
0.5424 Remote Similarity NPC481909
0.537 Remote Similarity NPC97516
0.5333 Remote Similarity NPC266957
0.5323 Remote Similarity NPC40746
0.5303 Remote Similarity NPC475819
0.5303 Remote Similarity NPC474232
0.5294 Remote Similarity NPC486030
0.5273 Remote Similarity NPC171204
0.5273 Remote Similarity NPC606745
0.5254 Remote Similarity NPC473390
0.5254 Remote Similarity NPC488296
0.5179 Remote Similarity NPC611318
0.5156 Remote Similarity NPC481911
0.5143 Remote Similarity NPC486032
0.5085 Remote Similarity NPC488302
0.5085 Remote Similarity NPC475461
0.5085 Remote Similarity NPC488300
0.5085 Remote Similarity NPC488301

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482126 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