Natural Product: NPC216478

Natural Product IDNPC216478
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-Sivasinolide
IUPAC Name (3aS,4R,4aS,8R,8aR,9aS)-4,8-dihydroxy-5,8a-dimethyl-3-methylidene-4,4a,7,8,9,9a-hexahydro-3aH-benzo[f][1]benzofuran-2-one
Synonyms (-)-Sivasinolide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL512455
PubChem CID 10333024
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:0001772] Eudesmanolides, secoeudesmanolides, 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 BICYHGOZXYLJIO-XFKURJONSA-N
Standard InCHI InChI=1S/C15H20O4/c1-7-4-5-10(16)15(3)6-9-11(13(17)12(7)15)8(2)14(18)19-9/h4,9-13,16-17H,2,5-6H2,1,3H3/t9-,10+,11+,12+,13-,15-/m0/s1
SMILES CC1=CC[C@H]([C@]2(C)C[C@H]3[C@@H](C(=C)C(=O)O3)[C@@H]([C@@H]12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   264.14 Volume:   269.578
?
Van der Waals volume.
Dense:   0.98 LogP:   1.284
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.396
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.194
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.392 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.823 Fsp3:   0.667
MCE-18:   52.8
?
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:   0.496 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.376
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.477 Promiscuous compounds:   0.313

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.313 MDCK Permeability:   -4.879
Pgp-inhibitor:   0.106 Pgp-substrate:   0.833
PAMPA:   0.91
?
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):   0.514
20% Bioavailability (F20%):   0.932 30% Bioavailability (F30%):   0.983
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.545 MRP1:   0.77
Plasma Protein Binding (PPB):   61.419% Volume Distribution (VD):   0.056
Fu: 39.002%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.049
BSEP inhibitor:   0.853

ADMET: Metabolism

CYP1A2-inhibitor:   0.01 CYP1A2-substrate:   0.128
CYP2C19-inhibitor:   0.086 CYP2C19-substrate:   0.19
CYP2C9-inhibitor:   0.033 CYP2C9-substrate:   0.082
CYP2D6-inhibitor:   0.013 CYP2D6-substrate:   0.171
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.589
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.546
HLM stability:   0.421
?
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):  6.431 Half-life (T1/2):  2.083

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.118
Human Hepatotoxicity (H-HT):  0.68 Drug-induced Liver Injury (DILI):  0.888
AMES Toxicity:  0.535 Rat Oral Acute Toxicity:  0.251
Maximum Recommended Daily Dose:  0.343 Skin Sensitization:  0.944
Carcinogencity:  0.697 Eye Corrosion:  0.064
Eye Irritation:  0.833 Respiratory Toxicity:  0.286
Drug-induced Neurotoxicity:  0.248 Ototoxicity:  0.746
Hematotoxicity:  0.497 Drug-induced Nephrotoxicity:  0.62
Genotoxicity:  0.579 RPMI-8226 Immunitoxicity:  0.067
A549 Cytotoxicity:  0.318 Hek293 Cytotoxicity:  0.176
BCF:   0.385
?
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:   3.025
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.457
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.694
?
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
NPO26031 Acacia auriculiformis Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/0031-9422(80)80226-3]
NPO11960 Myriastra clavosa Species n.a. n.a. n.a. Philippines n.a. PMID[12193033]
NPO11960 Myriastra clavosa Species n.a. n.a. n.a. n.a. n.a. PMID[12350152]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. PMID[12762812]
NPO15105 Lyngbya semiplena Species Oscillatoriaceae Bacteria n.a. Papua New Guinea n.a. PMID[14575438]
NPO26536 Garcinia humilis Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[15844964]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota Root Bark n.a. n.a. PMID[21985060]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. root n.a. PMID[21985060]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36987013]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38611827]
NPO19302 Amathia alternata Species Vesiculariidae Eukaryota n.a. Atlantic n.a. PMID[9249973]
NPO16082 Flindersia bennettiana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11070 Nervilia purpurea Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18669 Myriophyllum verticillatum Species Haloragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11960 Myriastra clavosa Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO13667 Manoao colensoi Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15105 Lyngbya semiplena Species Oscillatoriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO17744 Litsea elliptica Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18035 Lagerstroemia flos-reginae Species Lythraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14198 Haliclona valliculata Species Chalinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26981 Thunbergia laurifolia Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22538 Dendrobium plicatile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19302 Amathia alternata Species Vesiculariidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26454 Acacia oswaldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO25840 Sargassum fusiforme Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26379 Metrosideros umbellata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8746 Melaleuca triumphalis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26783 Jurinea eriobasis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25745 Grindelia arenicola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26536 Garcinia humilis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26658 Commiphora dalzielii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11310 Baorangia pseudocalopus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26431 Aplophyllum sieversii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO26031 Acacia auriculiformis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26136 Abuta racemosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18258 Zanthoxylum rhoifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19079 Vatica pauciflora Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14705 Tanacetopsis mucronata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13312 Senecio panduriformis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19237 Sargassum macrocarpum Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10039 Podosphaera fuliginea Species Erysiphaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO25840 Sargassum fusiforme Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25840 Sargassum fusiforme Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26431 Aplophyllum sieversii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO17744 Litsea elliptica Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18669 Myriophyllum verticillatum Species Haloragaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26783 Jurinea eriobasis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18258 Zanthoxylum rhoifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26981 Thunbergia laurifolia Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19237 Sargassum macrocarpum Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14705 Tanacetopsis mucronata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26658 Commiphora dalzielii Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11960 Myriastra clavosa Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO11070 Nervilia purpurea Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26136 Abuta racemosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14198 Haliclona valliculata Species Chalinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18035 Lagerstroemia flos-reginae Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10039 Podosphaera fuliginea Species Erysiphaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26454 Acacia oswaldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15105 Lyngbya semiplena Species Oscillatoriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO13667 Manoao colensoi Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12968 Crotalaria spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25745 Grindelia arenicola Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26379 Metrosideros umbellata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19079 Vatica pauciflora Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22538 Dendrobium plicatile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23205 Anthemis altissima Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26031 Acacia auriculiformis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16082 Flindersia bennettiana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8746 Melaleuca triumphalis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11310 Baorangia pseudocalopus Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13312 Senecio panduriformis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26268 Salvia aethiopis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26536 Garcinia humilis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19302 Amathia alternata Species Vesiculariidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25840 Sargassum fusiforme Species Sargassaceae 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
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC = 12.5 ug.mL-1 PMID[12762812]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 50.0 ug.mL-1 PMID[12762812]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 25.0 ug.mL-1 PMID[12762812]

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 NPC216478 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 NPC480113
0.6809 Remote Similarity NPC469596
0.6809 Remote Similarity NPC148000
0.6809 Remote Similarity NPC225474
0.5577 Remote Similarity NPC93245
0.5283 Remote Similarity NPC228766
0.5091 Remote Similarity NPC233345
0.5091 Remote Similarity NPC186363

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC216478 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