Natural Product: NPC223249

Natural Product IDNPC223249
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Oxacyclohexadecan-2-One
IUPAC Name oxacyclohexadecan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3560504
PubChem CID 235414
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues

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 FKUPPRZPSYCDRS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H28O2/c16-15-13-11-9-7-5-3-1-2-4-6-8-10-12-14-17-15/h1-14H2
SMILES O=C1CCCCCCCCCCCCCCO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   240.21 Volume:   274.384
?
Van der Waals volume.
Dense:   0.875 LogP:   4.966
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.431
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.178
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.578 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.351 Fsp3:   0.933
MCE-18:   7.862
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.026 Fluc inhibitor:   0.171
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.009
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.662

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.929 MDCK Permeability:   -4.864
Pgp-inhibitor:   0.688 Pgp-substrate:   0.0
PAMPA:   0.001
?
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):   0.0
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.019

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.989 MRP1:   0.913
Plasma Protein Binding (PPB):   78.45% Volume Distribution (VD):   0.025
Fu: 9.146%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.716
OATP1B3 inhibitor:   0.923 BCRP inhibitor:   0.055
BSEP inhibitor:   0.898

ADMET: Metabolism

CYP1A2-inhibitor:   0.493 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.013
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.01
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.009 CYP2C8-inhibitor:   0.389
HLM stability:   1.0
?
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):  5.484 Half-life (T1/2):  0.224

ADMET: Toxicity

hERG Blockers:  0.3 hERG Blockers (10um):  0.662
Human Hepatotoxicity (H-HT):  0.125 Drug-induced Liver Injury (DILI):  0.093
AMES Toxicity:  0.01 Rat Oral Acute Toxicity:  0.015
Maximum Recommended Daily Dose:  0.566 Skin Sensitization:  0.817
Carcinogencity:  0.081 Eye Corrosion:  0.912
Eye Irritation:  0.993 Respiratory Toxicity:  0.262
Drug-induced Neurotoxicity:  0.133 Ototoxicity:  0.13
Hematotoxicity:  0.084 Drug-induced Nephrotoxicity:  0.073
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.053
A549 Cytotoxicity:  0.145 Hek293 Cytotoxicity:  0.154
BCF:   1.4
?
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:   2.919
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.157
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.544
?
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
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1002/elan.200403102]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. DOI[10.1016/j.foodchem.2012.02.124]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. DOI[10.5012/bkcs.2003.24.11.1699]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[11077184]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[11374978]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[12510838]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[15646793]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[15679317]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flowers n.a. n.a. PMID[17328234]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[17997069]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[18321056]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[21657081]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower n.a. PMID[21804227]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. flower bud n.a. PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota flower buds Henan province, China 2005-MAY PMID[21942812]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. leaf n.a. PMID[23265495]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota Flower buds n.a. n.a. PMID[24279769]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27444348]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota Roots n.a. n.a. PMID[31464439]
NPO43457 Thymus holosericeus Genus Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36679061]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO58210 Anthemis palestina Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38005810]
NPO44392 Gynoxys reinaldii Genus Asteraceae Eukaryota n.a. n.a. n.a. PMID[39771242]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[7463094]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[8201313]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[8699182]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30823 Evodia rutaecarpa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30823 Evodia rutaecarpa n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30823 Evodia rutaecarpa n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19935 Evodia rutaecarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1515 Lonicera japonica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19935 Evodia rutaecarpa Species Rutaceae 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
NPO43457 Thymus holosericeus Oil n.a. 0.1 n.a. n.a. % PMID[36679061]
NPO43457 Thymus holosericeus Oil n.a. 0.02 n.a. n.a. % PMID[36679061]
NPO44392 Gynoxys reinaldii Oil n.a. 0.1 n.a. n.a. % PMID[39771242]
NPO58210 Anthemis palestina Shade-dried n.a. 0.14 n.a. n.a. % PMID[38005810]
NPO58210 Anthemis palestina Sun-dried n.a. 0.68 n.a. n.a. % PMID[38005810]
NPO58210 Anthemis palestina Oven-dried n.a. 0.37 n.a. n.a. % PMID[38005810]

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
NPT20556 Single protein Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = 12.5 % DOI[10.6019/CHEMBL4495564]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 14.88 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = -2.95 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT603 Individual protein Olfactory receptor 5K1 Homo sapiens Inhibition >= 40.0 % Patent: WO2013171535 A3

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 2.28 % DOI[10.21203/rs.3.rs-23951/v1]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = -0.1 % DOI[10.6019/CHEMBL4495565]
NPT2 Others Unspecified n.a. Potency n.a. 61130.6 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 NPC223249 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

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC223249 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

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