Natural Product: NPC543009

Natural Product IDNPC543009
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3~{a}~{S},6~{Z},10~{E},11~{a}~{S})-6,10-dimethyl-3-methylene-3~{a},4,5,8,9,11~{a}-hexahydrocyclodeca[b]furan-2-one
IUPAC Name (3~{a}~{S},6~{Z},10~{E},11~{a}~{S})-6,10-dimethyl-3-methylene-3~{a},4,5,8,9,11~{a}-hexahydrocyclodeca[b]furan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 HRYLQFBHBWLLLL-CCYBBOTNSA-N
Standard InCHI InChI=1S/C15H20O2/c1-10-5-4-6-11(2)9-14-13(8-7-10)12(3)15(16)17-14/h5,9,13-14H,3-4,6-8H2,1-2H3/b10-5-,11-9+/t13-,14-/m0/s1
SMILES C=C1C(=O)O[C@H]2/C=C(C)CC/C=C(/C)CC[C@@H]12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   232.15 Volume:   257.918
?
Van der Waals volume.
Dense:   0.9 LogP:   2.88
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.871
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.092
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   16.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.363 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.23 Fsp3:   0.533
MCE-18:   30.261
?
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:   0.326 Fluc inhibitor:   0.553
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.03
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.061
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.96 Promiscuous compounds:   0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.7 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.896 Pgp-substrate:   0.068
PAMPA:   0.156
?
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):   0.256
20% Bioavailability (F20%):   0.524 30% Bioavailability (F30%):   0.974
50% Bioavailability (F50%):   0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.77
Plasma Protein Binding (PPB):   94.975% Volume Distribution (VD):   0.032
Fu: 5.318%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.047
BSEP inhibitor:   0.981

ADMET: Metabolism

CYP1A2-inhibitor:   0.152 CYP1A2-substrate:   0.603
CYP2C19-inhibitor:   0.932 CYP2C19-substrate:   0.261
CYP2C9-inhibitor:   0.894 CYP2C9-substrate:   0.048
CYP2D6-inhibitor:   0.469 CYP2D6-substrate:   0.541
CYP3A4-inhibitor:   0.081 CYP3A4-substrate:   0.929
CYP2B6-substrate:   0.033 CYP2C8-inhibitor:   0.925
HLM stability:   0.887
?
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):  9.963 Half-life (T1/2):  1.586

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.15
Human Hepatotoxicity (H-HT):  0.758 Drug-induced Liver Injury (DILI):  0.892
AMES Toxicity:  0.255 Rat Oral Acute Toxicity:  0.161
Maximum Recommended Daily Dose:  0.623 Skin Sensitization:  0.994
Carcinogencity:  0.393 Eye Corrosion:  0.704
Eye Irritation:  0.943 Respiratory Toxicity:  0.085
Drug-induced Neurotoxicity:  0.517 Ototoxicity:  0.32
Hematotoxicity:  0.387 Drug-induced Nephrotoxicity:  0.62
Genotoxicity:  0.082 RPMI-8226 Immunitoxicity:  0.11
A549 Cytotoxicity:  0.184 Hek293 Cytotoxicity:  0.288
BCF:   2.103
?
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:   4.48
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.032
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.661
?
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
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. DOI[10.1080/10412905.2001.9699624]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[11912066]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. PMID[12419922]
NPO30603 Saussurea lappa n.a. n.a. n.a. n.a. root n.a. PMID[18409040]
NPO2192 Cortinarius subtortus Species Cortinariaceae Eukaryota fruiting bodies n.a. n.a. PMID[18447384]
NPO30603 Saussurea lappa n.a. n.a. n.a. roots n.a. n.a. PMID[18579374]
NPO9819 Dasyscyphus niveus Species Hyaloscyphaceae Eukaryota n.a. n.a. n.a. PMID[18771321]
NPO13590 Diploicia canescens Species Caliciaceae Eukaryota n.a. n.a. n.a. PMID[19919064]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. PMID[21188975]
NPO29375 Penicillium thomii Species Aspergillaceae Eukaryota n.a. Lazurnaya Bay, the Sea of Japan n.a. PMID[24852445]
NPO29375 Penicillium thomii Species Aspergillaceae Eukaryota n.a. isolated from superficial mycobiota of the brown alga Sargassum miyabei (Lazurnaya Bay, the Sea of Japan) n.a. PMID[24852445]
NPO30603 Saussurea lappa n.a. n.a. n.a. n.a. n.a. n.a. PMID[25068579]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[30813368]
NPO44372 Cosmos sulphureus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[36840242]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38695450]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38851735]
NPO30603 Saussurea lappa n.a. n.a. n.a. n.a. root n.a. PMID[8541643]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2192 Cortinarius subtortus Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30603 Saussurea lappa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO44372 Cosmos sulphureus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13590 Diploicia canescens Species Caliciaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25535 Cosmos pringlei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23739 Staehelina fruticosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56434 Talauma mexicana Genus Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO47659 Frullania rostrata Species Frullaniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50013 Frullania lobulata Species Frullaniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO62463 Artemisia genipy Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14634 Artemisia balchanorum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9819 Dasyscyphus niveus Species Hyaloscyphaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO43651 Magnolia virginiana Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14485 Eriocephalus kingesii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61809 Anthemis melampodina Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16260 Stevia yaconensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21571 Streptomyces cirratus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29375 Penicillium thomii Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10316 Glechoma longituba Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO10316 Glechoma longituba Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30603 Saussurea lappa n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10316 Glechoma longituba Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10316 Glechoma longituba Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10316 Glechoma longituba Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9819 Dasyscyphus niveus Species Hyaloscyphaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13590 Diploicia canescens Species Caliciaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21571 Streptomyces cirratus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO10316 Glechoma longituba Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2192 Cortinarius subtortus Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29375 Penicillium thomii Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14485 Eriocephalus kingesii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14634 Artemisia balchanorum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16260 Stevia yaconensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23739 Staehelina fruticosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25535 Cosmos pringlei 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

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 NPC543009 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 NPC58956
1.0 High Similarity NPC163003
1.0 High Similarity NPC295633
1.0 High Similarity NPC269206
0.8333 Intermediate Similarity NPC476355
0.814 Intermediate Similarity NPC7563
0.7174 Intermediate Similarity NPC123360
0.6977 Remote Similarity NPC140287
0.6939 Remote Similarity NPC93763
0.68 Remote Similarity NPC108816
0.6739 Remote Similarity NPC470256
0.6667 Remote Similarity NPC601805
0.6531 Remote Similarity NPC267231
0.6531 Remote Similarity NPC250315
0.6512 Remote Similarity NPC235906
0.6458 Remote Similarity NPC194871
0.6444 Remote Similarity NPC196653
0.6444 Remote Similarity NPC603669
0.6304 Remote Similarity NPC471465
0.6222 Remote Similarity NPC171204
0.6222 Remote Similarity NPC606745
0.6087 Remote Similarity NPC611318
0.6078 Remote Similarity NPC20713
0.6 Remote Similarity NPC167881
0.6 Remote Similarity NPC98557
0.5909 Remote Similarity NPC129665
0.5833 Remote Similarity NPC480697
0.551 Remote Similarity NPC38468
0.551 Remote Similarity NPC192678
0.551 Remote Similarity NPC319795
0.551 Remote Similarity NPC50362
0.551 Remote Similarity NPC488056
0.551 Remote Similarity NPC605079
0.5435 Remote Similarity NPC65603
0.5349 Remote Similarity NPC606552
0.5333 Remote Similarity NPC306041
0.5306 Remote Similarity NPC229825
0.5306 Remote Similarity NPC473715
0.5306 Remote Similarity NPC474760
0.5306 Remote Similarity NPC59097
0.5306 Remote Similarity NPC602858
0.5294 Remote Similarity NPC165383
0.5283 Remote Similarity NPC173609
0.5208 Remote Similarity NPC155587
0.5208 Remote Similarity NPC329852
0.5185 Remote Similarity NPC470755
0.5185 Remote Similarity NPC298801
0.5094 Remote Similarity NPC481909
0.5094 Remote Similarity NPC488117
0.5094 Remote Similarity NPC473619
0.5094 Remote Similarity NPC178702
0.5091 Remote Similarity NPC284902

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC543009 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
0.551 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