Natural Product: NPC26227

Natural Product IDNPC26227
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Alnusin
IUPAC Name 3,5,7-trihydroxy-6-methoxy-2-phenylchromen-4-one
Synonyms Alnusin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL254936
PubChem CID 12305751
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 HYBBOIHJQNYTGH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/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/h2-7,17,19-20H,1H3
SMILES COc1c(cc2c(c(=O)c(c(c3ccccc3)o2)O)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   2.18
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.215
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.364
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   100.13
?
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:   0.672 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.376 Fsp3:   0.062
MCE-18:   18.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.68 Fluc inhibitor:   0.536
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.735
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.564
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.469 Promiscuous compounds:   0.914

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.074 MDCK Permeability:   -4.777
Pgp-inhibitor:   0.976 Pgp-substrate:   0.077
PAMPA:   0.18
?
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):   0.015
20% Bioavailability (F20%):   0.012 30% Bioavailability (F30%):   0.497
50% Bioavailability (F50%):   0.927

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.053 MRP1:   0.935
Plasma Protein Binding (PPB):   98.937% Volume Distribution (VD):   -0.843
Fu: 0.474%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.888
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.977
BSEP inhibitor:   0.88

ADMET: Metabolism

CYP1A2-inhibitor:   0.747 CYP1A2-substrate:   0.791
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.973
CYP2C9-inhibitor:   0.968 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.982 CYP2D6-substrate:   0.077
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.062
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.984
?
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):  3.77 Half-life (T1/2):  1.09

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.478
Human Hepatotoxicity (H-HT):  0.437 Drug-induced Liver Injury (DILI):  0.816
AMES Toxicity:  0.488 Rat Oral Acute Toxicity:  0.473
Maximum Recommended Daily Dose:  0.554 Skin Sensitization:  0.678
Carcinogencity:  0.656 Eye Corrosion:  0.446
Eye Irritation:  0.988 Respiratory Toxicity:  0.65
Drug-induced Neurotoxicity:  0.083 Ototoxicity:  0.119
Hematotoxicity:  0.165 Drug-induced Nephrotoxicity:  0.07
Genotoxicity:  0.687 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.243 Hek293 Cytotoxicity:  0.344
BCF:   1.084
?
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:   3.926
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.722
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.46
?
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]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. Database[COCONUT]

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[19053514]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM PMID[25707014]
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM DrugMatrix in vitro pharmacology data
NPT453 Cell line HT-1080 Homo sapiens IC50 > 100000.0 nM PMID[18211005]
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 NPC26227 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
0.8163 Intermediate Similarity NPC44079
0.78 Intermediate Similarity NPC98661
0.6923 Remote Similarity NPC293183
0.6792 Remote Similarity NPC152042
0.6364 Remote Similarity NPC608038
0.6154 Remote Similarity NPC187432
0.6071 Remote Similarity NPC50403
0.6071 Remote Similarity NPC301123
0.5965 Remote Similarity NPC49824
0.5849 Remote Similarity NPC128216
0.5789 Remote Similarity NPC241838
0.5763 Remote Similarity NPC93376
0.5714 Remote Similarity NPC472438
0.5614 Remote Similarity NPC203891
0.5614 Remote Similarity NPC241498
0.5614 Remote Similarity NPC219330
0.5614 Remote Similarity NPC266960
0.5614 Remote Similarity NPC156222
0.5593 Remote Similarity NPC115798
0.5593 Remote Similarity NPC54394
0.5593 Remote Similarity NPC255350
0.5574 Remote Similarity NPC227192
0.5517 Remote Similarity NPC100887
0.5517 Remote Similarity NPC143799
0.5517 Remote Similarity NPC163524
0.5424 Remote Similarity NPC9609
0.5424 Remote Similarity NPC256283
0.541 Remote Similarity NPC125062
0.541 Remote Similarity NPC114377
0.537 Remote Similarity NPC93730
0.5345 Remote Similarity NPC284552
0.5345 Remote Similarity NPC609062
0.5333 Remote Similarity NPC200740
0.5333 Remote Similarity NPC83508
0.5333 Remote Similarity NPC159103
0.5333 Remote Similarity NPC29841
0.5273 Remote Similarity NPC299379
0.5254 Remote Similarity NPC201451
0.5254 Remote Similarity NPC87125
0.5254 Remote Similarity NPC28274
0.5254 Remote Similarity NPC605146
0.5254 Remote Similarity NPC605755
0.5246 Remote Similarity NPC609179
0.5161 Remote Similarity NPC252933
0.5152 Remote Similarity NPC65491
0.5085 Remote Similarity NPC184536
0.5082 Remote Similarity NPC166753
0.5082 Remote Similarity NPC605826
0.5075 Remote Similarity NPC488750
0.5075 Remote Similarity NPC213622
0.5075 Remote Similarity NPC606048

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC26227 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
0.5593 Remote Similarity NPD2801 Pre-clinical

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