Natural Product: NPC472534

Natural Product IDNPC472534
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Shinjulactone A
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL349383
PubChem CID 44375396
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0002119] Quassinoids

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 RSGAOKBKALIZEE-RSIVDQDWSA-N
Standard InCHI InChI=1S/C20H26O7/c1-8-4-12(21)16(24)18(3)10(8)5-13-19-7-26-20(25,17(18)19)15(23)9(2)11(19)6-14(22)27-13/h4,10-13,15-17,21,23-25H,2,5-7H2,1,3H3/t10-,11-,12-,13+,15-,16+,17+,18+,19+,20-/m0/s1
SMILES O=C1O[C@@H]2C[C@H]3C(=C[C@@H]([C@H]([C@@]3([C@@H]3[C@@]42[C@@H](C1)C(=C)[C@@H]([C@@]3(OC4)O)O)C)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   378.17 Volume:   365.316
?
Van der Waals volume.
Dense:   1.035 LogP:   0.958
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.439
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.398
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   25.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.343 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.667 Fsp3:   0.75
MCE-18:   127.257
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.422 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.015
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.128 Promiscuous compounds:   0.507

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.483 MDCK Permeability:   -4.864
Pgp-inhibitor:   0.0 Pgp-substrate:   0.976
PAMPA:   0.999
?
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):   0.036
20% Bioavailability (F20%):   0.521 30% Bioavailability (F30%):   0.873
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.141 MRP1:   0.638
Plasma Protein Binding (PPB):   49.83% Volume Distribution (VD):   -0.186
Fu: 53.7%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.043
BSEP inhibitor:   0.008

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.122
HLM stability:   0.027
?
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):  5.46 Half-life (T1/2):  2.593

ADMET: Toxicity

hERG Blockers:  0.013 hERG Blockers (10um):  0.126
Human Hepatotoxicity (H-HT):  0.508 Drug-induced Liver Injury (DILI):  0.698
AMES Toxicity:  0.917 Rat Oral Acute Toxicity:  0.767
Maximum Recommended Daily Dose:  0.67 Skin Sensitization:  0.999
Carcinogencity:  0.576 Eye Corrosion:  0.002
Eye Irritation:  0.794 Respiratory Toxicity:  0.735
Drug-induced Neurotoxicity:  0.524 Ototoxicity:  0.672
Hematotoxicity:  0.327 Drug-induced Nephrotoxicity:  0.976
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.522
A549 Cytotoxicity:  0.178 Hek293 Cytotoxicity:  0.38
BCF:   0.353
?
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:   3.08
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.706
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.733
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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
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. xylem n.a. DOI[10.1248/cpb.24.1532]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[22224661]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[22799262]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[23290052]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota stem barks n.a. n.a. PMID[25666824]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15443 Ailanthus altissima Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15443 Ailanthus altissima Species Simaroubaceae 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
NPT759 Cell line H9 Homo sapiens IC50 = 5000.0 nM PubChem BioAssay data set
NPT65 Cell line HepG2 Homo sapiens IC50 > 50000.0 nM PMID[20498317]
NPT65 Cell line HepG2 Homo sapiens IC50 = 4670.0 nM PMID[17698618]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 56400.0 nM PMID[19015352]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 8010.0 nM PMID[23290052]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 5000.0 nM PubChem BioAssay data set

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 NPC472534 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
0.7377 Intermediate Similarity NPC51978
0.7213 Intermediate Similarity NPC143706
0.6912 Remote Similarity NPC470919
0.6812 Remote Similarity NPC474046
0.6716 Remote Similarity NPC488559
0.6364 Remote Similarity NPC302146
0.5921 Remote Similarity NPC122971
0.5833 Remote Similarity NPC469877
0.5753 Remote Similarity NPC470628
0.5753 Remote Similarity NPC608244
0.56 Remote Similarity NPC259306
0.5217 Remote Similarity NPC201992
0.5143 Remote Similarity NPC604470

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472534 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