Natural Product: NPC57405

Natural Product IDNPC57405
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RZUCCKARTVHQBW-MPFAERRBSA-N
IUPAC Name n.a.
Synonyms 9Beta-Hydroxyparthenolide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL462949
PubChem CID 14466188
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 RZUCCKARTVHQBW-MPFAERRBSA-N
Standard InCHI InChI=1S/C15H20O4/c1-8-5-4-6-15(3)13(19-15)12-10(7-11(8)16)9(2)14(17)18-12/h5,10-13,16H,2,4,6-7H2,1,3H3/b8-5+/t10-,11-,12-,13-,15+/m0/s1
SMILES C/C/1=CCC[C@]2(C)[C@H]([C@@H]3[C@@H](C[C@@H]1O)C(=C)C(=O)O3)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   264.14 Volume:   269.578
?
Van der Waals volume.
Dense:   0.98 LogP:   1.541
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.71
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.824
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   59.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.313 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.034 Fsp3:   0.667
MCE-18:   50.16
?
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:   0.474 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.008
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.475 Promiscuous compounds:   0.37

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.173 MDCK Permeability:   -4.881
Pgp-inhibitor:   0.402 Pgp-substrate:   0.399
PAMPA:   0.954
?
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):   0.378
20% Bioavailability (F20%):   0.902 30% Bioavailability (F30%):   0.961
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.022 MRP1:   0.643
Plasma Protein Binding (PPB):   61.126% Volume Distribution (VD):   0.139
Fu: 38.58%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.22
BSEP inhibitor:   0.866

ADMET: Metabolism

CYP1A2-inhibitor:   0.805 CYP1A2-substrate:   0.052
CYP2C19-inhibitor:   0.83 CYP2C19-substrate:   0.042
CYP2C9-inhibitor:   0.531 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.03 CYP2D6-substrate:   0.102
CYP3A4-inhibitor:   0.638 CYP3A4-substrate:   0.144
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.022
HLM stability:   0.371
?
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):  11.342 Half-life (T1/2):  1.503

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.187
Human Hepatotoxicity (H-HT):  0.706 Drug-induced Liver Injury (DILI):  0.803
AMES Toxicity:  0.816 Rat Oral Acute Toxicity:  0.671
Maximum Recommended Daily Dose:  0.496 Skin Sensitization:  0.998
Carcinogencity:  0.732 Eye Corrosion:  0.201
Eye Irritation:  0.898 Respiratory Toxicity:  0.348
Drug-induced Neurotoxicity:  0.61 Ototoxicity:  0.545
Hematotoxicity:  0.581 Drug-induced Nephrotoxicity:  0.829
Genotoxicity:  0.723 RPMI-8226 Immunitoxicity:  0.122
A549 Cytotoxicity:  0.539 Hek293 Cytotoxicity:  0.35
BCF:   0.858
?
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:   3.469
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.131
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.504
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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
NPO24419 Anvillea garcinii Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[11087618]
NPO24419 Anvillea garcinii Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[8699183]
NPO24419 Anvillea garcinii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24419 Anvillea garcinii 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
NPT404 Cell line CCRF-CEM Homo sapiens ED50 = 0.8 ug ml-1 PMID[25536852]
NPT112 Cell line MOLT-4 Homo sapiens ED50 = 0.68 ug ml-1 PMID[24953601]
NPT379 Cell line HOP-62 Homo sapiens ED50 = 4.57 ug ml-1 DrugMatrix in vivo data: Pathology
NPT455 Cell line NCI-H522 Homo sapiens ED50 = 0.45 ug ml-1 DrugMatrix in vivo data: Pathology
NPT393 Cell line HCT-116 Homo sapiens ED50 = 3.83 ug ml-1 DrugMatrix in vivo data: Pathology
NPT323 Cell line SW-620 Homo sapiens ED50 = 0.55 ug ml-1 PubChem BioAssay data set
NPT395 Cell line SF-268 Homo sapiens ED50 = 7.76 ug ml-1 DrugMatrix in vivo data: Pathology
NPT392 Cell line SNB-75 Homo sapiens ED50 = 8.53 ug ml-1 DrugMatrix in vivo data: Pathology
NPT390 Cell line LOX IMVI Homo sapiens ED50 = 2.46 ug ml-1 DrugMatrix in vivo data: Pathology
NPT375 Cell line Malme-3M Homo sapiens ED50 = 1.62 ug ml-1 DrugMatrix in vivo data: Pathology
NPT458 Cell line IGROV-1 Homo sapiens ED50 = 3.91 ug ml-1 DrugMatrix in vivo data: Pathology
NPT381 Cell line OVCAR-8 Homo sapiens ED50 = 4.75 ug ml-1 DrugMatrix in vivo data: Pathology
NPT369 Cell line ACHN Homo sapiens ED50 = 2.21 ug ml-1 PMID[12880316]
NPT371 Cell line UO-31 Homo sapiens ED50 = 3.88 ug ml-1 PMID[12880316]
NPT90 Cell line DU-145 Homo sapiens ED50 = 5.6 ug ml-1 PMID[12880316]
NPT82 Cell line MDA-MB-231 Homo sapiens ED50 = 4.99 ug ml-1 PMID[12880316]
NPT5027 Cell line Hs 683 Homo sapiens IC50 = 25000.0 nM PMID[17253840]
NPT81 Cell line A549 Homo sapiens IC50 = 24000.0 nM DrugMatrix in vitro pharmacology data
NPT83 Cell line MCF7 Homo sapiens IC50 = 23000.0 nM PMID[12932130]
NPT170 Cell line SK-MEL-28 Homo sapiens IC50 = 25000.0 nM PubChem BioAssay data set
NPT1125 Cell line T98G Homo sapiens IC50 = 25000.0 nM PMID[18672864]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 15000.0 nM PMID[24998377]

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 NPC57405 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 NPC303942
0.6604 Remote Similarity NPC608845
0.6346 Remote Similarity NPC38468
0.6346 Remote Similarity NPC192678
0.6346 Remote Similarity NPC319795
0.6346 Remote Similarity NPC50362
0.6346 Remote Similarity NPC488056
0.6346 Remote Similarity NPC605079
0.6226 Remote Similarity NPC49342
0.6226 Remote Similarity NPC251385
0.6207 Remote Similarity NPC473859
0.6034 Remote Similarity NPC475659
0.6 Remote Similarity NPC70251
0.6 Remote Similarity NPC475881
0.5932 Remote Similarity NPC487572
0.569 Remote Similarity NPC471147
0.5424 Remote Similarity NPC481908
0.5424 Remote Similarity NPC481993
0.5263 Remote Similarity NPC151770
0.5161 Remote Similarity NPC474035
0.5161 Remote Similarity NPC81386

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC57405 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
0.6346 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