Natural Product: NPC133771

Natural Product IDNPC133771
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (4R)-4-Hydroxy-4-Methyloxan-2-One
IUPAC Name (4R)-4-hydroxy-4-methyloxan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1401520
PubChem CID 6419891
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000050] Lactones
        • [CHEMONTID:0001244] Delta valerolactones

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 JYVXNLLUYHCIIH-ZCFIWIBFSA-N
Standard InCHI InChI=1S/C6H10O3/c1-6(8)2-3-9-5(7)4-6/h8H,2-4H2,1H3/t6-/m1/s1
SMILES C[C@]1(CCOC(=O)C1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   130.06 Volume:   127.51
?
Van der Waals volume.
Dense:   1.02 LogP:   -0.398
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.17
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.365
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   7.0
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:   0.472 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.525 Fsp3:   0.833
MCE-18:   19.091
?
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:   0.004 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.04
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.99 Promiscuous compounds:   0.402

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.633 MDCK Permeability:   -4.768
Pgp-inhibitor:   0.57 Pgp-substrate:   0.149
PAMPA:   0.921
?
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):   0.315
20% Bioavailability (F20%):   0.329 30% Bioavailability (F30%):   0.731
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.053 MRP1:   0.426
Plasma Protein Binding (PPB):   13.463% Volume Distribution (VD):   -0.008
Fu: 86.85%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.914
BSEP inhibitor:   0.901

ADMET: Metabolism

CYP1A2-inhibitor:   0.529 CYP1A2-substrate:   0.005
CYP2C19-inhibitor:   0.914 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.033 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.04
CYP3A4-inhibitor:   0.953 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.01
HLM stability:   0.069
?
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):  8.882 Half-life (T1/2):  2.587

ADMET: Toxicity

hERG Blockers:  0.018 hERG Blockers (10um):  0.081
Human Hepatotoxicity (H-HT):  0.533 Drug-induced Liver Injury (DILI):  0.049
AMES Toxicity:  0.226 Rat Oral Acute Toxicity:  0.038
Maximum Recommended Daily Dose:  0.142 Skin Sensitization:  0.891
Carcinogencity:  0.739 Eye Corrosion:  0.846
Eye Irritation:  0.995 Respiratory Toxicity:  0.086
Drug-induced Neurotoxicity:  0.164 Ototoxicity:  0.323
Hematotoxicity:  0.233 Drug-induced Nephrotoxicity:  0.904
Genotoxicity:  0.007 RPMI-8226 Immunitoxicity:  0.024
A549 Cytotoxicity:  0.003 Hek293 Cytotoxicity:  0.021
BCF:   0.164
?
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:   2.1
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.503
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.617
?
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
NPO28230 Stemona japonica Species Stemonaceae Eukaryota stems and leaves n.a. n.a. PMID[18163592]
NPO16660 Phomopsis archeri Species Valsaceae Eukaryota n.a. mycelium n.a. PMID[21341709]
NPO29474 Bipolaris victoriae Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28407 Clausena heptaphylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28178 Artemisia tridentata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16660 Phomopsis archeri Species Valsaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28560 Sarcomelicope glauca Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28407 Clausena heptaphylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28178 Artemisia tridentata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28560 Sarcomelicope glauca Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28178 Artemisia tridentata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28407 Clausena heptaphylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28407 Clausena heptaphylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28350 Hypsizigus marmoreus n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28230 Stemona japonica Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28108 Stereum princeps Species Stereaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28407 Clausena heptaphylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29474 Bipolaris victoriae Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27851 Leptothorax muscorum Species Formicidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28560 Sarcomelicope glauca Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28463 Penicillium gilmanii Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28178 Artemisia tridentata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23206 Senegalia caffra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16660 Phomopsis archeri Species Valsaceae 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
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 14125.4 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set

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 NPC133771 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 NPC133771 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