Natural Product: NPC327103

Natural Product IDNPC327103
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Hydroxy-2,3-Dimethyl-2H-Furan-5-One
IUPAC Name 4-hydroxy-2,3-dimethyl-2H-furan-5-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3185688
PubChem CID 62835
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001983] Dihydrofurans
        • [CHEMONTID:0001982] Furanones
          • [CHEMONTID:0002223] Butenolides

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 UNYNVICDCJHOPO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C6H8O3/c1-3-4(2)9-6(8)5(3)7/h4,7H,1-2H3
SMILES CC1C(=C(C(=O)O1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   128.05 Volume:   124.874
?
Van der Waals volume.
Dense:   1.025 LogP:   0.159
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.249
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.169
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   6.0
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:   0.49 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.575 Fsp3:   0.5
MCE-18:   15.556
?
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:   0.103 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.031
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.035
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.996 Promiscuous compounds:   0.01

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.591 MDCK Permeability:   -4.481
Pgp-inhibitor:   0.1 Pgp-substrate:   0.373
PAMPA:   0.533
?
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):   0.262
20% Bioavailability (F20%):   0.673 30% Bioavailability (F30%):   0.904
50% Bioavailability (F50%):   0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.471 MRP1:   0.966
Plasma Protein Binding (PPB):   31.786% Volume Distribution (VD):   -0.279
Fu: 61.005%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.907
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.11
BSEP inhibitor:   0.542

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.564
CYP2C19-inhibitor:   0.143 CYP2C19-substrate:   0.21
CYP2C9-inhibitor:   0.55 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.014 CYP2D6-substrate:   0.441
CYP3A4-inhibitor:   0.922 CYP3A4-substrate:   0.037
CYP2B6-substrate:   0.299 CYP2C8-inhibitor:   0.169
HLM stability:   0.98
?
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):  6.672 Half-life (T1/2):  1.832

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.12
Human Hepatotoxicity (H-HT):  0.508 Drug-induced Liver Injury (DILI):  0.817
AMES Toxicity:  0.448 Rat Oral Acute Toxicity:  0.296
Maximum Recommended Daily Dose:  0.095 Skin Sensitization:  0.915
Carcinogencity:  0.605 Eye Corrosion:  0.942
Eye Irritation:  0.996 Respiratory Toxicity:  0.362
Drug-induced Neurotoxicity:  0.269 Ototoxicity:  0.268
Hematotoxicity:  0.428 Drug-induced Nephrotoxicity:  0.664
Genotoxicity:  0.36 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.014 Hek293 Cytotoxicity:  0.03
BCF:   0.299
?
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:   2.777
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.149
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.345
?
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
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. n.a. PMID[ 10835233]
NPO19774 Rubus idaeus Species n.a. n.a. Fruit n.a. n.a. DOI[10.1016/S0963-9969(99)00095-2]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11599360]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[17019935]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. seed n.a. PMID[21381697]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[21381697]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. n.a. PMID[21381697]
NPO659 Secale cereale Species Poaceae Eukaryota n.a. n.a. n.a. PMID[21381697]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[37120447]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. n.a. PMID[37570937]
NPO47860 Gonystylus bancanus Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[37709800]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. PMID[38397470]
NPO47860 Gonystylus bancanus Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[38802441]
NPO659 Secale cereale Species Poaceae Eukaryota n.a. n.a. n.a. PMID[9134744]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO659 Secale cereale Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19774 Rubus idaeus Species n.a. n.a. Leaf n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO659 Secale cereale Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO19774 Rubus idaeus Species n.a. n.a. Fruits n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO19774 Rubus idaeus Species n.a. n.a. Seed n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO19774 Rubus idaeus Species n.a. n.a. Fruit n.a. n.a. Database[FooDB]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO659 Secale cereale Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO659 Secale cereale Species Poaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO659 Secale cereale Species Poaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. Database[Phenol-Explorer]
NPO19774 Rubus idaeus Species n.a. n.a. Fruits n.a. Database[Phenol-Explorer]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2413 Saccharum officinarum Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8210 Trigonella foenum-graecum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19774 Rubus idaeus Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO659 Secale cereale Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2413 Saccharum officinarum Species Poaceae 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
NPO47860 Gonystylus bancanus Dichloro methane extract n.a. 0.21 n.a. n.a. % PMID[37709800]
NPO47860 Gonystylus bancanus Ethyl acetate extract n.a. 0.24 n.a. n.a. % PMID[37709800]
NPO47860 Gonystylus bancanus Methanol extract n.a. 0.22 n.a. n.a. % PMID[37709800]

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
NPT2 Others Unspecified n.a. Potency n.a. 1.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 21.7 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 NPC327103 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 NPC327103 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