Natural Product: NPC310210

Natural Product IDNPC310210
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (6R)-3,7-Dimethyl-7-Hydroxy-2-Octen-6-Olide
IUPAC Name (2R)-2-(2-hydroxypropan-2-yl)-5-methyl-3,4-dihydro-2H-oxepin-7-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2271745
PubChem CID 76319759
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000129] Alcohols and polyols
          • [CHEMONTID:0001670] Tertiary alcohols

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 ICSVRXLISHBJRU-MRVPVSSYSA-N
Standard InCHI InChI=1S/C10H16O3/c1-7-4-5-8(10(2,3)12)13-9(11)6-7/h6,8,12H,4-5H2,1-3H3/t8-/m1/s1
SMILES CC1=CC(=O)O[C@H](CC1)C(O)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   184.11 Volume:   194.058
?
Van der Waals volume.
Dense:   0.949 LogP:   0.456
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.499
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.817
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   8.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.627 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.476 Fsp3:   0.7
MCE-18:   21.176
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.05 Fluc inhibitor:   0.121
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.101
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.005
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.967 Promiscuous compounds:   0.531

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.872 MDCK Permeability:   -4.679
Pgp-inhibitor:   0.108 Pgp-substrate:   0.149
PAMPA:   0.437
?
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):   0.01
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.012
50% Bioavailability (F50%):   0.06

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.106 MRP1:   0.712
Plasma Protein Binding (PPB):   32.344% Volume Distribution (VD):   -0.162
Fu: 66.534%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.949 BCRP inhibitor:   0.046
BSEP inhibitor:   0.67

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.338
CYP2C19-inhibitor:   0.996 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.987 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.946 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.044 CYP3A4-substrate:   0.022
CYP2B6-substrate:   0.991 CYP2C8-inhibitor:   0.725
HLM stability:   0.068
?
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):  5.895 Half-life (T1/2):  1.603

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.179
Human Hepatotoxicity (H-HT):  0.585 Drug-induced Liver Injury (DILI):  0.347
AMES Toxicity:  0.419 Rat Oral Acute Toxicity:  0.12
Maximum Recommended Daily Dose:  0.098 Skin Sensitization:  0.997
Carcinogencity:  0.815 Eye Corrosion:  0.818
Eye Irritation:  0.974 Respiratory Toxicity:  0.112
Drug-induced Neurotoxicity:  0.433 Ototoxicity:  0.324
Hematotoxicity:  0.429 Drug-induced Nephrotoxicity:  0.843
Genotoxicity:  0.293 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.012 Hek293 Cytotoxicity:  0.059
BCF:   0.199
?
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:   2.358
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.797
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.083
?
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
NPO27883 Bursera simaruba Species Burseraceae Eukaryota Resin n.a. n.a. PMID[1294696]
NPO28935 Ericameria laricifolia Species Asteraceae Eukaryota n.a. Sonoran Desert n.a. PMID[15043404]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. aerial part n.a. PMID[18991207]
NPO27883 Bursera simaruba Species Burseraceae Eukaryota n.a. bark n.a. PMID[19329133]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota essential oil Tibet n.a. PMID[20944522]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota Twigs n.a. n.a. PMID[28541690]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[36552598]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[37746728]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39013008]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39395223]
NPO27903 Delphinium denudatum Species Ranunculaceae Eukaryota n.a. root n.a. PMID[9170290]
NPO28959 Cissus quadrangularis Species Vitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29411 Streptomyces nigrescens Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO27883 Bursera simaruba Species Burseraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29377 Callistemon speciosus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16079 Cephalaria leucantha Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1079 Vachellia karroo Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27562 Coleus wulfenioides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27903 Delphinium denudatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18780 Diplacus aurantiacus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28935 Ericameria laricifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26851 Eupatorium rebaudianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29307 Loranthus longiflorus Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28549 Mentha incana Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29144 Ormosia fordiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO862 Podocarpus elatus Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26549 Polanisia trachysperma Species Cleomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27724 Polygala senega Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29218 Ramalina farinacea Species Ramalinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27256 Solanum boerhaavii Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26851 Eupatorium rebaudianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27903 Delphinium denudatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27724 Polygala senega Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1079 Vachellia karroo Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27903 Delphinium denudatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26851 Eupatorium rebaudianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27724 Polygala senega Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18780 Diplacus aurantiacus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27724 Polygala senega Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27724 Polygala senega Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29411 Streptomyces nigrescens Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26851 Eupatorium rebaudianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26549 Polanisia trachysperma Species Cleomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28959 Cissus quadrangularis Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29377 Callistemon speciosus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29218 Ramalina farinacea Species Ramalinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29144 Ormosia fordiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28935 Ericameria laricifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27903 Delphinium denudatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27883 Bursera simaruba Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO862 Podocarpus elatus Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29307 Loranthus longiflorus Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27724 Polygala senega Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16079 Cephalaria leucantha Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1079 Vachellia karroo Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18780 Diplacus aurantiacus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28549 Mentha incana Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27256 Solanum boerhaavii Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27562 Coleus wulfenioides Species Lamiaceae 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
NPT5263 Organism Pseudocercospora musae Pseudocercospora musae Inhibition = 65.5 % PMID[20944522]
NPT5869 Organism Colletotrichum lindemuthianum Colletotrichum lindemuthianum Inhibition = 62.3 % PMID[20944522]
NPT1503 Organism Verticillium dahliae Verticillium dahliae Inhibition = 66.6 % PMID[20944522]
NPT825 Organism Phytophthora infestans Phytophthora infestans Inhibition = 66.4 % PMID[20944522]
NPT2781 Organism Fusarium moniliforme Gibberella moniliformis Inhibition = 55.6 % PMID[20944522]
NPT962 Organism Alternaria alternata Alternaria alternata Inhibition = 70.9 % PMID[20944522]
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana Inhibition = 72.0 % PMID[20944522]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum IC50 = 151.25 ug.mL-1 PMID[20944522]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 81.8 % PMID[20944522]
NPT637 Organism Fusarium oxysporum Fusarium oxysporum Inhibition = 53.5 % PMID[20944522]
NPT1494 Organism Alternaria mali Alternaria mali Inhibition = 66.0 % PMID[20944522]
NPT2976 Organism Thanatephorus cucumeris Thanatephorus cucumeris IC50 = 115.58 ug.mL-1 PMID[20944522]
NPT562 Organism Colletotrichum gloeosporioides Colletotrichum gloeosporioides Inhibition = 71.1 % PMID[20944522]
NPT2976 Organism Thanatephorus cucumeris Thanatephorus cucumeris Inhibition = 80.2 % PMID[20944522]
NPT1276 Organism Gibberella zeae Gibberella zeae Inhibition = 73.8 % PMID[20944522]

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 NPC310210 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC310210 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