Natural Product: NPC162476

Natural Product IDNPC162476
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6-Hydroxyacetyl-5-Hydroxy-2,2-Dimethyl-2H-Chromene
IUPAC Name 2-hydroxy-1-(5-hydroxy-2,2-dimethylchromen-6-yl)ethanone
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2047549
PubChem CID 59051355
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0003522] 2,2-dimethyl-1-benzopyrans

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 KIOAAZWXERJXQO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H14O4/c1-13(2)6-5-9-11(17-13)4-3-8(12(9)16)10(15)7-14/h3-6,14,16H,7H2,1-2H3
SMILES CC1(C)C=Cc2c(ccc(C(=O)CO)c2O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   234.09 Volume:   238.27
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Van der Waals volume.
Dense:   0.982 LogP:   2.468
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.566
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.78
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   12.0
TPSA:   66.76
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.765 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.843 Fsp3:   0.308
MCE-18:   29.647
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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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.117 Fluc inhibitor:   0.502
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.456
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.219
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.646 Promiscuous compounds:   0.477

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.877 MDCK Permeability:   -4.669
Pgp-inhibitor:   0.355 Pgp-substrate:   0.072
PAMPA:   0.641
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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):   0.056
20% Bioavailability (F20%):   0.355 30% Bioavailability (F30%):   0.581
50% Bioavailability (F50%):   0.929

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.465 MRP1:   0.58
Plasma Protein Binding (PPB):   87.023% Volume Distribution (VD):   -0.015
Fu: 14.336%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.967
OATP1B3 inhibitor:   0.935 BCRP inhibitor:   0.278
BSEP inhibitor:   0.94

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.007
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.049
CYP2C9-inhibitor:   0.545 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.213
CYP3A4-inhibitor:   0.017 CYP3A4-substrate:   0.017
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.874
HLM stability:   0.875
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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):  5.07 Half-life (T1/2):  1.682

ADMET: Toxicity

hERG Blockers:  0.059 hERG Blockers (10um):  0.319
Human Hepatotoxicity (H-HT):  0.358 Drug-induced Liver Injury (DILI):  0.144
AMES Toxicity:  0.634 Rat Oral Acute Toxicity:  0.315
Maximum Recommended Daily Dose:  0.273 Skin Sensitization:  0.51
Carcinogencity:  0.558 Eye Corrosion:  0.089
Eye Irritation:  0.968 Respiratory Toxicity:  0.888
Drug-induced Neurotoxicity:  0.215 Ototoxicity:  0.384
Hematotoxicity:  0.307 Drug-induced Nephrotoxicity:  0.191
Genotoxicity:  0.143 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.077 Hek293 Cytotoxicity:  0.213
BCF:   0.955
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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:   3.564
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.15
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.438
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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
NPO33370 brickellia cavanillesii Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[22587572]

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
NPT1648 Individual protein Oligo-1,6-glucosidase Saccharomyces cerevisiae S288c IC50 = 420000.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 = 420000.0 nM PMID[11473432]
NPT2 Others Unspecified n.a. Ki = 130000.0 nM PMID[22652254]

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 NPC162476 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
0.8293 Intermediate Similarity NPC609512
0.6538 Remote Similarity NPC305355
0.6415 Remote Similarity NPC156590
0.6182 Remote Similarity NPC118840
0.6071 Remote Similarity NPC205006
0.5965 Remote Similarity NPC606276
0.5965 Remote Similarity NPC608781
0.5763 Remote Similarity NPC234255
0.5667 Remote Similarity NPC94155
0.5484 Remote Similarity NPC6118
0.52 Remote Similarity NPC151113

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC162476 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