Natural Product: NPC253303

Natural Product IDNPC253303
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4(15)-Eudesmene-1Beta,7Alpha-Diol
IUPAC Name (1R,4aS,6S,8aR)-8a-methyl-4-methylidene-6-propan-2-yl-2,3,4a,5,7,8-hexahydro-1H-naphthalene-1,6-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL501913
PubChem CID 11470456
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0000101] Eudesmane, isoeudesmane or cycloeudesmane sesquiterpenoids

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 SWIPEIJPNVNEPT-YJNKXOJESA-N
Standard InCHI InChI=1S/C15H26O2/c1-10(2)15(17)8-7-14(4)12(9-15)11(3)5-6-13(14)16/h10,12-13,16-17H,3,5-9H2,1-2,4H3/t12-,13+,14+,15-/m0/s1
SMILES C=C1CC[C@H]([C@]2([C@H]1C[C@@](O)(CC2)C(C)C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   238.19 Volume:   265.827
?
Van der Waals volume.
Dense:   0.896 LogP:   2.284
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.473
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.424
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   12.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.69 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.315 Fsp3:   0.867
MCE-18:   42.286
?
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:   0.051 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.011
?
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:   0.859 Promiscuous compounds:   0.249

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.505 MDCK Permeability:   -4.535
Pgp-inhibitor:   0.434 Pgp-substrate:   0.606
PAMPA:   0.472
?
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):   0.001
20% Bioavailability (F20%):   0.214 30% Bioavailability (F30%):   0.288
50% Bioavailability (F50%):   0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.107 MRP1:   0.811
Plasma Protein Binding (PPB):   74.771% Volume Distribution (VD):   0.071
Fu: 26.258%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.796
BSEP inhibitor:   0.849

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.093
CYP2C19-inhibitor:   0.629 CYP2C19-substrate:   0.067
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.081
CYP2D6-inhibitor:   0.358 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.901 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.239
HLM stability:   0.755
?
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):  17.032 Half-life (T1/2):  2.644

ADMET: Toxicity

hERG Blockers:  0.073 hERG Blockers (10um):  0.34
Human Hepatotoxicity (H-HT):  0.69 Drug-induced Liver Injury (DILI):  0.042
AMES Toxicity:  0.195 Rat Oral Acute Toxicity:  0.217
Maximum Recommended Daily Dose:  0.658 Skin Sensitization:  0.561
Carcinogencity:  0.828 Eye Corrosion:  0.039
Eye Irritation:  0.903 Respiratory Toxicity:  0.296
Drug-induced Neurotoxicity:  0.142 Ototoxicity:  0.508
Hematotoxicity:  0.136 Drug-induced Nephrotoxicity:  0.519
Genotoxicity:  0.046 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.115 Hek293 Cytotoxicity:  0.259
BCF:   0.227
?
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:   2.641
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.11
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.199
?
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
NPO25111 Streptomyces tanashiensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. DOI[10.1016/S0040-4039(01)84249-0]
NPO4501 Caragana intermedia Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15620236]
NPO24121 Vernoniopsis caudata n.a. n.a. n.a. n.a. n.a. n.a. PMID[15921436]
NPO20815 Lindera fruticosa Species Lauraceae Eukaryota roots n.a. n.a. PMID[16724860]
NPO29956 Sanicula lamelligera Species Apiaceae Eukaryota Whole plants Mountain Emei, Sichuan Province, China 2008-OCT PMID[21561060]
NPO29956 Sanicula lamelligera Species Apiaceae Eukaryota n.a. whole plant n.a. PMID[21561060]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[26509914]
NPO16971 Sparassis crispa Species Sparassidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21683 Selaginella lepidophylla Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25111 Streptomyces tanashiensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23376 Genista aetnensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23843 Clerodendrum grayi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20815 Lindera fruticosa Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14448 Laurencia venusta Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23948 Serratia plymuthica Species Yersiniaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22722 Ranunculus japonicus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22722 Ranunculus japonicus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22722 Ranunculus japonicus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18589 Allopora californica n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO23948 Serratia plymuthica Species Yersiniaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO24776 Euryops jacksonii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13388 Lithophyllum incrustans Species Corallinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20226 Artemisia filatovae Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24411 Pentaspadon motleyi Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23676 Fleroya rubrostipulata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20815 Lindera fruticosa Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14448 Laurencia venusta Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23843 Clerodendrum grayi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23158 Penicillium carminoviolaceum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24121 Vernoniopsis caudata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO23376 Genista aetnensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17668 Artemisia gmelinii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4501 Caragana intermedia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25111 Streptomyces tanashiensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO22713 Aquilegia flabellata Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20936 Arecastrum romanzoffianum n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO21683 Selaginella lepidophylla Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16184 Asclepias asperula Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21121 Ips japonicus Species Curculionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16971 Sparassis crispa Species Sparassidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23445 Vernonia triflosculosa 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
NPT83 Cell line MCF7 Homo sapiens IC50 > 64400.0 nM PMID[21561060]
NPT81 Cell line A549 Homo sapiens IC50 > 64400.0 nM PMID[21561060]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 > 64400.0 nM PMID[21561060]
NPT116 Cell line HL-60 Homo sapiens IC50 > 64400.0 nM PMID[21561060]
NPT113 Cell line RAW264.7 Mus musculus IC50 > 64400.0 nM PMID[21561060]
NPT660 Cell line SW480 Homo sapiens IC50 > 64400.0 nM PMID[21561060]
NPT1452 Cell line C8166 Homo sapiens CC50 > 420200.0 nM PMID[21561060]
NPT826 Organism Magnaporthe oryzae Magnaporthe oryzae MIC = 12.0 ug.mL-1 PMID[15620236]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 > 420200.0 nM PMID[21561060]

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 NPC253303 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 NPC269077
0.75 Intermediate Similarity NPC309048
0.5641 Remote Similarity NPC608659
0.561 Remote Similarity NPC101128
0.561 Remote Similarity NPC95165

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC253303 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