Natural Product: NPC20488

Natural Product IDNPC20488
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Buceracidin B
IUPAC Name (8S)-5-hydroxy-8-(2-hydroxyphenyl)-2,2-dimethyl-7,8-dihydropyrano[3,2-g]chromen-6-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL462932
PubChem CID 44584124
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0003520] Pyranoflavonoids

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 CTXOXNJBBDQWCE-HNNXBMFYSA-N
Standard InCHI InChI=1S/C20H18O5/c1-20(2)8-7-12-16(25-20)10-17-18(19(12)23)14(22)9-15(24-17)11-5-3-4-6-13(11)21/h3-8,10,15,21,23H,9H2,1-2H3/t15-/m0/s1
SMILES O=C1C[C@H](Oc2c1c(O)c1c(c2)OC(C=C1)(C)C)c1ccccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.12 Volume:   343.11
?
Van der Waals volume.
Dense:   0.985 LogP:   3.891
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.528
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.608
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.822 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.366 Fsp3:   0.25
MCE-18:   77.76
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.615 Fluc inhibitor:   0.683
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.568
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.42
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.29 Promiscuous compounds:   0.159

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.916 MDCK Permeability:   -4.716
Pgp-inhibitor:   0.998 Pgp-substrate:   0.015
PAMPA:   0.783
?
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):   0.016
20% Bioavailability (F20%):   0.05 30% Bioavailability (F30%):   0.988
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.926
Plasma Protein Binding (PPB):   97.347% Volume Distribution (VD):   0.022
Fu: 2.367%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.995
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.092 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.968
CYP2C9-inhibitor:   0.912 CYP2C9-substrate:   0.052
CYP2D6-inhibitor:   0.121 CYP2D6-substrate:   0.6
CYP3A4-inhibitor:   0.699 CYP3A4-substrate:   0.209
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.987
HLM stability:   0.995
?
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):  5.601 Half-life (T1/2):  0.992

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.455
Human Hepatotoxicity (H-HT):  0.738 Drug-induced Liver Injury (DILI):  0.364
AMES Toxicity:  0.755 Rat Oral Acute Toxicity:  0.636
Maximum Recommended Daily Dose:  0.691 Skin Sensitization:  0.876
Carcinogencity:  0.534 Eye Corrosion:  0.003
Eye Irritation:  0.983 Respiratory Toxicity:  0.444
Drug-induced Neurotoxicity:  0.6 Ototoxicity:  0.377
Hematotoxicity:  0.147 Drug-induced Nephrotoxicity:  0.787
Genotoxicity:  0.88 RPMI-8226 Immunitoxicity:  0.258
A549 Cytotoxicity:  0.521 Hek293 Cytotoxicity:  0.538
BCF:   1.652
?
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:   4.277
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.142
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.302
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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
NPO24957 Bucida buceras Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[12542360]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. PMID[34946632]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. PMID[38370218]
NPO24957 Bucida buceras Species Combretaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14464 Oxalis triangularis Species Oxalidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28353 Schizanthus pinnatus Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28564 Pterorhachis zenkeri Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28411 Hedysarum setigerum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24957 Bucida buceras Species Combretaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11029 Bessera tenuiflora Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28235 Heimia montana Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28353 Schizanthus pinnatus Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14464 Oxalis triangularis Species Oxalidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28113 Oria flava n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28736 Wedelia paludosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28183 Cymbopogon flexuosus 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

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
NPT91 Cell line KB Homo sapiens IC50 = 9.5 ug.mL-1 PMID[12542360]
NPT81 Cell line A549 Homo sapiens IC50 = 9.9 ug.mL-1 PMID[12542360]
NPT309 Cell line 1A9 Homo sapiens IC50 = 11.5 ug.mL-1 PMID[12542360]
NPT180 Cell line HCT-8 Homo sapiens IC50 = 12.8 ug.mL-1 PMID[12542360]
NPT83 Cell line MCF7 Homo sapiens IC50 = 9.3 ug.mL-1 PMID[12542360]
NPT306 Cell line PC-3 Homo sapiens IC50 = 13.0 ug.mL-1 PMID[12542360]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 = 14.0 ug.mL-1 PMID[12542360]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 9.5 ug.mL-1 PMID[12542360]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 14.2 ug.mL-1 PMID[12542360]

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 NPC20488 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
0.8167 Intermediate Similarity NPC470647
0.6667 Remote Similarity NPC67805
0.6567 Remote Similarity NPC311579
0.5467 Remote Similarity NPC195621
0.5397 Remote Similarity NPC107586
0.5395 Remote Similarity NPC54577
0.5362 Remote Similarity NPC176229
0.5333 Remote Similarity NPC267375
0.5256 Remote Similarity NPC488550
0.5224 Remote Similarity NPC11561
0.5205 Remote Similarity NPC88964
0.52 Remote Similarity NPC472633
0.5195 Remote Similarity NPC83357
0.5135 Remote Similarity NPC483807
0.5132 Remote Similarity NPC214774
0.5077 Remote Similarity NPC324134
0.5077 Remote Similarity NPC40833
0.5072 Remote Similarity NPC306829
0.5065 Remote Similarity NPC488549

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC20488 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