Natural Product: NPC275316

Natural Product IDNPC275316
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (+)-(6S)-Parasorbic Acid
IUPAC Name (2S)-2-methyl-2,3-dihydropyran-6-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2252704
PubChem CID 441575
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000086] Pyrans
        • [CHEMONTID:0000481] Pyranones and derivatives
          • [CHEMONTID:0001211] Dihydropyranones

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 DYNKRGCMLGUEMN-YFKPBYRVSA-N
Standard InCHI InChI=1S/C6H8O2/c1-5-3-2-4-6(7)8-5/h2,4-5H,3H2,1H3/t5-/m0/s1
SMILES C[C@H]1CC=CC(=O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   112.05 Volume:   116.083
?
Van der Waals volume.
Dense:   0.965 LogP:   0.826
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.885
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.675
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   7.0
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:   0.435 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.356 Fsp3:   0.5
MCE-18:   12.222
?
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:   0.044 Fluc inhibitor:   0.656
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.496

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.629 MDCK Permeability:   -4.587
Pgp-inhibitor:   0.363 Pgp-substrate:   0.194
PAMPA:   0.58
?
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):   0.031
20% Bioavailability (F20%):   0.495 30% Bioavailability (F30%):   0.717
50% Bioavailability (F50%):   0.524

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.053 MRP1:   0.892
Plasma Protein Binding (PPB):   11.822% Volume Distribution (VD):   -0.089
Fu: 87.253%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.926
OATP1B3 inhibitor:   0.891 BCRP inhibitor:   0.036
BSEP inhibitor:   0.936

ADMET: Metabolism

CYP1A2-inhibitor:   0.033 CYP1A2-substrate:   0.034
CYP2C19-inhibitor:   0.252 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.095 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.038
CYP3A4-inhibitor:   0.079 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.154 CYP2C8-inhibitor:   0.379
HLM stability:   0.631
?
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):  5.676 Half-life (T1/2):  2.031

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.355
Human Hepatotoxicity (H-HT):  0.231 Drug-induced Liver Injury (DILI):  0.483
AMES Toxicity:  0.646 Rat Oral Acute Toxicity:  0.491
Maximum Recommended Daily Dose:  0.302 Skin Sensitization:  0.96
Carcinogencity:  0.589 Eye Corrosion:  0.999
Eye Irritation:  0.999 Respiratory Toxicity:  0.554
Drug-induced Neurotoxicity:  0.453 Ototoxicity:  0.135
Hematotoxicity:  0.269 Drug-induced Nephrotoxicity:  0.408
Genotoxicity:  0.236 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.075 Hek293 Cytotoxicity:  0.104
BCF:   0.433
?
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:   2.866
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.933
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.396
?
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
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20020118]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1556/abot.45.2003.3-4.15]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[15019787]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[18177011]
NPO30240 Bergenia ligulata Species Saxifragaceae Eukaryota n.a. n.a. n.a. PMID[18622126]
NPO13029 Sorbus aucuparia Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[18635332]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[19271742]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[20590154]
NPO14376 Stephania cephalantha Species Menispermaceae Eukaryota n.a. stem n.a. PMID[21214233]
NPO14376 Stephania cephalantha Species Menispermaceae Eukaryota n.a. leaf n.a. PMID[21214233]
NPO30240 Bergenia ligulata Species Saxifragaceae Eukaryota volatile oil n.a. n.a. PMID[21639116]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22029392]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[23517479]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[32872604]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[36352904]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[37685099]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39679248]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39680258]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[8064299]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[8064299]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27640 Sorbus tianschanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30240 Bergenia ligulata Species Saxifragaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14376 Stephania cephalantha Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13029 Sorbus aucuparia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO13029 Sorbus aucuparia Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Resin, Exudate, Sap n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27640 Sorbus tianschanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13029 Sorbus aucuparia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19669 Papaver album Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO13029 Sorbus aucuparia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19669 Papaver album Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14376 Stephania cephalantha Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27640 Sorbus tianschanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13029 Sorbus aucuparia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27640 Sorbus tianschanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19669 Papaver album Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27640 Sorbus tianschanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7282 Rauvolfia serpentina Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13029 Sorbus aucuparia Species Rosaceae 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
- Drosophila melanogaster LD50 = 1.44 ug PMID[21639116]

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 NPC275316 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
0.5357 Remote Similarity NPC159650

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC275316 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