Natural Product: NPC263449

Natural Product IDNPC263449
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Alnustinol
IUPAC Name (2R,3R)-3,5,7-trihydroxy-6-methoxy-2-phenyl-2,3-dihydrochromen-4-one
Synonyms Alnustinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL252704
PubChem CID 44446838
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-O-methylated flavonoids

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 HFDPLPWGKGPTJB-LSDHHAIUSA-N
Standard InCHI InChI=1S/C16H14O6/c1-21-16-9(17)7-10-11(13(16)19)12(18)14(20)15(22-10)8-5-3-2-4-6-8/h2-7,14-15,17,19-20H,1H3/t14-,15+/m0/s1
SMILES COc1c(O)cc2c(c1O)C(=O)[C@@H]([C@H](O2)c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.08 Volume:   293.909
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Van der Waals volume.
Dense:   1.028 LogP:   1.501
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.645
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.926
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   96.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.782 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.202 Fsp3:   0.188
MCE-18:   57.789
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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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.44 Fluc inhibitor:   0.53
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.173
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.249
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.313 Promiscuous compounds:   0.105

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.704 MDCK Permeability:   -4.867
Pgp-inhibitor:   0.969 Pgp-substrate:   0.163
PAMPA:   0.273
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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):   0.018
20% Bioavailability (F20%):   0.007 30% Bioavailability (F30%):   0.808
50% Bioavailability (F50%):   0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.219 MRP1:   0.816
Plasma Protein Binding (PPB):   98.112% Volume Distribution (VD):   -0.413
Fu: 1.369%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.98
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.529
BSEP inhibitor:   0.548

ADMET: Metabolism

CYP1A2-inhibitor:   0.964 CYP1A2-substrate:   0.231
CYP2C19-inhibitor:   0.02 CYP2C19-substrate:   0.059
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.085 CYP2D6-substrate:   0.4
CYP3A4-inhibitor:   0.498 CYP3A4-substrate:   0.067
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.323
HLM stability:   0.748
?
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):  5.46 Half-life (T1/2):  1.551

ADMET: Toxicity

hERG Blockers:  0.087 hERG Blockers (10um):  0.468
Human Hepatotoxicity (H-HT):  0.931 Drug-induced Liver Injury (DILI):  0.57
AMES Toxicity:  0.598 Rat Oral Acute Toxicity:  0.63
Maximum Recommended Daily Dose:  0.333 Skin Sensitization:  0.996
Carcinogencity:  0.306 Eye Corrosion:  0.007
Eye Irritation:  0.979 Respiratory Toxicity:  0.314
Drug-induced Neurotoxicity:  0.751 Ototoxicity:  0.347
Hematotoxicity:  0.411 Drug-induced Nephrotoxicity:  0.916
Genotoxicity:  0.802 RPMI-8226 Immunitoxicity:  0.197
A549 Cytotoxicity:  0.749 Hek293 Cytotoxicity:  0.466
BCF:   0.825
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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:   3.443
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.702
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.156
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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
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[17950610]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[18440233]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[26938776]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[32525315]
NPO8300 Apis mellifera ligustica Species Apidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8300 Apis mellifera ligustica Species Apidae Eukaryota n.a. n.a. n.a. Database[TCMID]

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
NPT461 Cell line PANC-1 Homo sapiens CD100 > 100.0 uM PMID[17950610]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM PMID[18440233]
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PMID[18440233]
NPT453 Cell line HT-1080 Homo sapiens IC50 > 100000.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[18440233]

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 NPC263449 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
0.6923 Remote Similarity NPC308992
0.6731 Remote Similarity NPC122828
0.6538 Remote Similarity NPC4152
0.6346 Remote Similarity NPC476182
0.6111 Remote Similarity NPC255106
0.6111 Remote Similarity NPC235165
0.6038 Remote Similarity NPC148011
0.6 Remote Similarity NPC481903
0.5965 Remote Similarity NPC42892
0.5714 Remote Similarity NPC44721
0.5714 Remote Similarity NPC211466
0.5714 Remote Similarity NPC605332
0.566 Remote Similarity NPC31704
0.5614 Remote Similarity NPC250922
0.5439 Remote Similarity NPC176869
0.5439 Remote Similarity NPC3779
0.5424 Remote Similarity NPC320825
0.5357 Remote Similarity NPC62290
0.5357 Remote Similarity NPC142731
0.5357 Remote Similarity NPC326506
0.5357 Remote Similarity NPC105136
0.5345 Remote Similarity NPC609065
0.5263 Remote Similarity NPC201837
0.5246 Remote Similarity NPC326037
0.5246 Remote Similarity NPC13858
0.5091 Remote Similarity NPC1940

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC263449 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