Natural Product: NPC481994

Natural Product IDNPC481994
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NGGWPCQJJXMSHR-WSFMCSFISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 9974897
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 NGGWPCQJJXMSHR-WSFMCSFISA-N
Standard InCHI InChI=1S/C19H22O6/c1-10(2)17(21)23-13-8-12(9-20)6-5-7-19(4)16(25-19)15-14(13)11(3)18(22)24-15/h6,9,13-16H,1,3,5,7-8H2,2,4H3/b12-6-/t13-,14+,15-,16-,19+/m0/s1
SMILES C=C(C)C(=O)O[C@H]1C/C(=C/CC[C@]2(C)[C@H]([C@@H]3[C@@H]1C(=C)C(=O)O3)O2)/C=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.14 Volume:   348.433
?
Van der Waals volume.
Dense:   0.993 LogP:   2.648
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.789
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.491
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   21.0
TPSA:   82.2
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.337 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.177 Fsp3:   0.526
MCE-18:   53.586
?
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:   0.536 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.018
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.158
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.447 Promiscuous compounds:   0.231

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.904 MDCK Permeability:   -4.681
Pgp-inhibitor:   0.956 Pgp-substrate:   0.006
PAMPA:   0.402
?
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):   0.16
20% Bioavailability (F20%):   0.721 30% Bioavailability (F30%):   0.991
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.112
Plasma Protein Binding (PPB):   51.613% Volume Distribution (VD):   0.205
Fu: 50.074%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.152
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.063 CYP1A2-substrate:   0.132
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.086
CYP2C9-inhibitor:   0.674 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.043 CYP3A4-substrate:   0.435
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.526
HLM stability:   0.477
?
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):  8.579 Half-life (T1/2):  1.264

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.23
Human Hepatotoxicity (H-HT):  0.665 Drug-induced Liver Injury (DILI):  0.938
AMES Toxicity:  0.707 Rat Oral Acute Toxicity:  0.228
Maximum Recommended Daily Dose:  0.659 Skin Sensitization:  0.998
Carcinogencity:  0.834 Eye Corrosion:  0.906
Eye Irritation:  0.98 Respiratory Toxicity:  0.262
Drug-induced Neurotoxicity:  0.463 Ototoxicity:  0.299
Hematotoxicity:  0.223 Drug-induced Nephrotoxicity:  0.471
Genotoxicity:  0.758 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.053 Hek293 Cytotoxicity:  0.352
BCF:   1.176
?
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:   3.846
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.704
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.133
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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
NPO4240 Elephantopus tomentosus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[10075766]
NPO4240 Elephantopus tomentosus Species Asteraceae Eukaryota n.a. stem n.a. PMID[18239317]
NPO4240 Elephantopus tomentosus Species Asteraceae Eukaryota n.a. root n.a. PMID[18239317]
NPO4240 Elephantopus tomentosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4240 Elephantopus tomentosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4240 Elephantopus tomentosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4240 Elephantopus tomentosus 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
NPT91 Cell line KB Homo sapiens ED50 = 2.7 ug ml-1 PMID[10075766]

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 NPC481994 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 NPC481908
0.7547 Intermediate Similarity NPC481993
0.7115 Intermediate Similarity NPC151770
0.6607 Remote Similarity NPC605339
0.6333 Remote Similarity NPC288876
0.6271 Remote Similarity NPC483718
0.5862 Remote Similarity NPC473330
0.5645 Remote Similarity NPC279561
0.5517 Remote Similarity NPC5130
0.5424 Remote Similarity NPC150755
0.5323 Remote Similarity NPC483935
0.5263 Remote Similarity NPC38468
0.5263 Remote Similarity NPC192678
0.5263 Remote Similarity NPC319795
0.5263 Remote Similarity NPC50362
0.5263 Remote Similarity NPC488056
0.5263 Remote Similarity NPC605079
0.5238 Remote Similarity NPC264477
0.5172 Remote Similarity NPC49342
0.5172 Remote Similarity NPC251385

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC481994 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
0.5263 Remote Similarity NPD1733 Clinical (unspecified phase)

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