Natural Product: NPC482133

Natural Product IDNPC482133
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RDTSNPPYNHHXLZ-IDSHBCFPSA-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 RDTSNPPYNHHXLZ-IDSHBCFPSA-N
Standard InCHI InChI=1S/C22H28O8/c1-6-15(10-23)22(27)30-18-7-11(2)16(25)9-17(28-14(5)24)12(3)8-19-20(18)13(4)21(26)29-19/h6,8,16-20,23,25H,2,4,7,9-10H2,1,3,5H3/b12-8-,15-6-/t16-,17+,18-,19-,20-/m1/s1
SMILES C/C=C(/CO)C(=O)O[C@@H]1CC(=C)[C@@H](C[C@@H](/C(=C[C@@H]2[C@@H]1C(=C)C(=O)O2)/C)OC(=O)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   420.18 Volume:   423.822
?
Van der Waals volume.
Dense:   0.991 LogP:   0.891
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.145
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.324
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   20.0
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:   5.248 Fsp3:   0.5
MCE-18:   43.636
?
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:   0.717 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.028
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.013
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.575 Promiscuous compounds:   0.509

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.932 MDCK Permeability:   -4.721
Pgp-inhibitor:   0.892 Pgp-substrate:   0.942
PAMPA:   0.661
?
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):   0.434
20% Bioavailability (F20%):   0.961 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.917
Plasma Protein Binding (PPB):   78.766% Volume Distribution (VD):   -0.115
Fu: 19.885%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.215
BSEP inhibitor:   0.977

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.07 CYP3A4-substrate:   0.092
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.536
?
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):  7.739 Half-life (T1/2):  1.167

ADMET: Toxicity

hERG Blockers:  0.004 hERG Blockers (10um):  0.05
Human Hepatotoxicity (H-HT):  0.901 Drug-induced Liver Injury (DILI):  0.965
AMES Toxicity:  0.916 Rat Oral Acute Toxicity:  0.168
Maximum Recommended Daily Dose:  0.6 Skin Sensitization:  0.995
Carcinogencity:  0.931 Eye Corrosion:  0.004
Eye Irritation:  0.649 Respiratory Toxicity:  0.043
Drug-induced Neurotoxicity:  0.212 Ototoxicity:  0.82
Hematotoxicity:  0.643 Drug-induced Nephrotoxicity:  0.953
Genotoxicity:  0.972 RPMI-8226 Immunitoxicity:  0.158
A549 Cytotoxicity:  0.222 Hek293 Cytotoxicity:  0.139
BCF:   0.463
?
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:   3.16
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.024
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.284
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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 NPC482133 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
0.8491 Intermediate Similarity NPC482134
0.7143 Intermediate Similarity NPC482128
0.7143 Intermediate Similarity NPC482129
0.6667 Remote Similarity NPC482126
0.65 Remote Similarity NPC134725
0.65 Remote Similarity NPC48657
0.6441 Remote Similarity NPC482127
0.6271 Remote Similarity NPC482130
0.623 Remote Similarity NPC230800
0.5902 Remote Similarity NPC269509
0.5862 Remote Similarity NPC488302
0.5862 Remote Similarity NPC475461
0.5862 Remote Similarity NPC488300
0.5862 Remote Similarity NPC488301
0.5833 Remote Similarity NPC287089
0.5789 Remote Similarity NPC476028
0.5758 Remote Similarity NPC486033
0.5692 Remote Similarity NPC96018
0.5593 Remote Similarity NPC116543
0.5574 Remote Similarity NPC482131
0.5556 Remote Similarity NPC486031
0.5484 Remote Similarity NPC470755
0.5484 Remote Similarity NPC298801
0.5455 Remote Similarity NPC486037
0.5362 Remote Similarity NPC59330
0.5312 Remote Similarity NPC488304
0.5224 Remote Similarity NPC486034
0.5161 Remote Similarity NPC481909
0.5156 Remote Similarity NPC471141
0.5082 Remote Similarity NPC250940
0.5082 Remote Similarity NPC169575
0.5079 Remote Similarity NPC266957

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482133 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