Natural Product: NPC482131

Natural Product IDNPC482131
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MUZYRVFSXXFTOF-IMYVKFHPSA-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 MUZYRVFSXXFTOF-IMYVKFHPSA-N
Standard InCHI InChI=1S/C22H28O7/c1-6-13(3)21(25)28-18-9-12(2)7-8-17(27-15(5)24)16(11-23)10-19-20(18)14(4)22(26)29-19/h6-7,10,17-20,23H,4,8-9,11H2,1-3,5H3/b12-7+,13-6+,16-10-/t17-,18+,19+,20+/m0/s1
SMILES C/C=C(C)/C(=O)O[C@@H]1C/C(=C/C[C@@H](/C(=C[C@@H]2[C@@H]1C(=C)C(=O)O2)/CO)OC(=O)C)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   404.18 Volume:   415.032
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Van der Waals volume.
Dense:   0.974 LogP:   2.001
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.246
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.139
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   99.13
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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:   4.959 Fsp3:   0.5
MCE-18:   40.182
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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:   0.309 Fluc inhibitor:   0.019
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.047
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.03
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.6 Promiscuous compounds:   0.365

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.883 MDCK Permeability:   -4.697
Pgp-inhibitor:   0.465 Pgp-substrate:   0.815
PAMPA:   0.774
?
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):   0.462
20% Bioavailability (F20%):   0.796 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.967
Plasma Protein Binding (PPB):   68.094% Volume Distribution (VD):   -0.276
Fu: 26.743%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.023
BSEP inhibitor:   0.868

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.025
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.038
CYP2C9-inhibitor:   0.307 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.237
CYP3A4-inhibitor:   0.206 CYP3A4-substrate:   0.054
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.982
HLM stability:   0.718
?
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):  8.152 Half-life (T1/2):  0.942

ADMET: Toxicity

hERG Blockers:  0.003 hERG Blockers (10um):  0.051
Human Hepatotoxicity (H-HT):  0.646 Drug-induced Liver Injury (DILI):  0.956
AMES Toxicity:  0.686 Rat Oral Acute Toxicity:  0.24
Maximum Recommended Daily Dose:  0.48 Skin Sensitization:  1.0
Carcinogencity:  0.775 Eye Corrosion:  0.26
Eye Irritation:  0.696 Respiratory Toxicity:  0.12
Drug-induced Neurotoxicity:  0.193 Ototoxicity:  0.374
Hematotoxicity:  0.592 Drug-induced Nephrotoxicity:  0.863
Genotoxicity:  0.946 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.282 Hek293 Cytotoxicity:  0.299
BCF:   0.619
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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:   3.411
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.358
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.533
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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 NPC482131 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
0.898 High Similarity NPC482130
0.7547 Intermediate Similarity NPC482128
0.7547 Intermediate Similarity NPC482129
0.7407 Intermediate Similarity NPC269509
0.7143 Intermediate Similarity NPC134725
0.7143 Intermediate Similarity NPC48657
0.7059 Intermediate Similarity NPC476028
0.678 Remote Similarity NPC482132
0.6379 Remote Similarity NPC482134
0.623 Remote Similarity NPC486034
0.6182 Remote Similarity NPC250940
0.6182 Remote Similarity NPC116543
0.6182 Remote Similarity NPC169575
0.614 Remote Similarity NPC482126
0.614 Remote Similarity NPC266957
0.6038 Remote Similarity NPC611318
0.6032 Remote Similarity NPC486033
0.5968 Remote Similarity NPC486037
0.5965 Remote Similarity NPC158756
0.5965 Remote Similarity NPC601035
0.5818 Remote Similarity NPC270126
0.5763 Remote Similarity NPC470755
0.5763 Remote Similarity NPC298801
0.5667 Remote Similarity NPC482127
0.5667 Remote Similarity NPC469910
0.5574 Remote Similarity NPC486031
0.5574 Remote Similarity NPC482133
0.5556 Remote Similarity NPC171204
0.5556 Remote Similarity NPC606745
0.5455 Remote Similarity NPC488306
0.5424 Remote Similarity NPC481909
0.5424 Remote Similarity NPC488298
0.537 Remote Similarity NPC97516
0.5345 Remote Similarity NPC488302
0.5345 Remote Similarity NPC475461
0.5345 Remote Similarity NPC488300
0.5345 Remote Similarity NPC488301
0.5323 Remote Similarity NPC40746
0.5263 Remote Similarity NPC609300
0.5254 Remote Similarity NPC473321
0.5254 Remote Similarity NPC488296
0.5167 Remote Similarity NPC488297
0.5161 Remote Similarity NPC471141
0.5156 Remote Similarity NPC481911
0.5143 Remote Similarity NPC486032
0.5072 Remote Similarity NPC486030

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482131 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