Natural Product: NPC12175

Natural Product IDNPC12175
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Xenognosin B
IUPAC Name 7-hydroxy-3-(2-hydroxy-4-methoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL253514
PubChem CID 5280551
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0002687] 4'-O-methylisoflavones

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 XKHHKXCBFHUOHM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O5/c1-20-10-3-5-11(14(18)7-10)13-8-21-15-6-9(17)2-4-12(15)16(13)19/h2-8,17-18H,1H3
SMILES COc1ccc(c2coc3cc(ccc3c2=O)O)c(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.07 Volume:   282.482
?
Van der Waals volume.
Dense:   1.006 LogP:   2.181
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.377
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.274
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.756 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.232 Fsp3:   0.062
MCE-18:   17.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.422 Fluc inhibitor:   0.997
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.925
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.581
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.596 Promiscuous compounds:   0.726

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.864 MDCK Permeability:   -4.805
Pgp-inhibitor:   0.057 Pgp-substrate:   0.137
PAMPA:   0.127
?
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):   0.049
20% Bioavailability (F20%):   0.589 30% Bioavailability (F30%):   0.878
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.428
Plasma Protein Binding (PPB):   91.791% Volume Distribution (VD):   -0.124
Fu: 10.518%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.862
OATP1B3 inhibitor:   0.983 BCRP inhibitor:   0.952
BSEP inhibitor:   0.629

ADMET: Metabolism

CYP1A2-inhibitor:   0.995 CYP1A2-substrate:   0.908
CYP2C19-inhibitor:   0.091 CYP2C19-substrate:   0.377
CYP2C9-inhibitor:   0.977 CYP2C9-substrate:   0.991
CYP2D6-inhibitor:   0.99 CYP2D6-substrate:   0.461
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.739
CYP2B6-substrate:   0.207 CYP2C8-inhibitor:   0.997
HLM stability:   0.263
?
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):  4.205 Half-life (T1/2):  1.47

ADMET: Toxicity

hERG Blockers:  0.159 hERG Blockers (10um):  0.542
Human Hepatotoxicity (H-HT):  0.43 Drug-induced Liver Injury (DILI):  0.609
AMES Toxicity:  0.648 Rat Oral Acute Toxicity:  0.516
Maximum Recommended Daily Dose:  0.765 Skin Sensitization:  0.299
Carcinogencity:  0.75 Eye Corrosion:  0.161
Eye Irritation:  0.991 Respiratory Toxicity:  0.866
Drug-induced Neurotoxicity:  0.308 Ototoxicity:  0.187
Hematotoxicity:  0.125 Drug-induced Nephrotoxicity:  0.221
Genotoxicity:  0.845 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.288 Hek293 Cytotoxicity:  0.637
BCF:   1.103
?
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:   3.755
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.46
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.021
?
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
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jfca.2005.08.001]
NPO31008 Ardisia colorata Species Primulaceae Eukaryota n.a. fruit n.a. PMID[11767097]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15286289]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[17950610]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18039011]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[18440233]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18460139]
NPO31008 Ardisia colorata Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[19124248]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19124248]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. seed n.a. PMID[20947202]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23743282]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24253552]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[26938776]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28522265]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[29641206]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[32525315]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[8987503]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9525107]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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]
NPO31008 Ardisia colorata Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Wax n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Tissue Culture n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31008 Ardisia colorata Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11043 Pisum sativum Species Fabaceae Eukaryota Seeds n.a. Database[Phenol-Explorer]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8300 Apis mellifera ligustica Species Apidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11043 Pisum sativum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1698 Glycyrrhiza inflata Species Fabaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 47.0 % PMID[28522265]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 2.28 n.a. PMID[28835349]

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 = 69800.0 nM PMID[18440233]
NPT453 Cell line HT-1080 Homo sapiens IC50 > 100000.0 nM PMID[18440233]
NPT579 Cell line DLD-1 Homo sapiens Activity = 2.5 n.a. PMID[19124248]
NPT83 Cell line MCF7 Homo sapiens GI = 1.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 13.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 0.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 1.0 % PMID[28522265]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 49300.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 34100.0 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 NPC12175 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
0.7636 Intermediate Similarity NPC209560
0.7636 Intermediate Similarity NPC490700
0.7544 Intermediate Similarity NPC195763
0.7241 Intermediate Similarity NPC100263
0.7241 Intermediate Similarity NPC156953
0.7119 Intermediate Similarity NPC55162
0.7119 Intermediate Similarity NPC291802
0.6949 Remote Similarity NPC279668
0.6949 Remote Similarity NPC40290
0.6909 Remote Similarity NPC235428
0.678 Remote Similarity NPC12377
0.6724 Remote Similarity NPC609386
0.6667 Remote Similarity NPC80710
0.6667 Remote Similarity NPC191741
0.6557 Remote Similarity NPC200060
0.6462 Remote Similarity NPC611071
0.6441 Remote Similarity NPC203747
0.6393 Remote Similarity NPC139364
0.623 Remote Similarity NPC262623
0.6071 Remote Similarity NPC234560
0.6029 Remote Similarity NPC266572
0.5938 Remote Similarity NPC35544
0.5915 Remote Similarity NPC605730
0.5862 Remote Similarity NPC242893
0.5797 Remote Similarity NPC149875
0.5758 Remote Similarity NPC215375
0.5738 Remote Similarity NPC10467
0.5714 Remote Similarity NPC121527
0.5714 Remote Similarity NPC104555
0.569 Remote Similarity NPC212767
0.5672 Remote Similarity NPC607759
0.5645 Remote Similarity NPC181124
0.5634 Remote Similarity NPC609101
0.5522 Remote Similarity NPC161124
0.5484 Remote Similarity NPC266597
0.5397 Remote Similarity NPC69430
0.5397 Remote Similarity NPC121522
0.5385 Remote Similarity NPC90665
0.5342 Remote Similarity NPC7989
0.5333 Remote Similarity NPC258035
0.5323 Remote Similarity NPC487215
0.5323 Remote Similarity NPC608872
0.5238 Remote Similarity NPC281207
0.5238 Remote Similarity NPC603503
0.5211 Remote Similarity NPC610903
0.5205 Remote Similarity NPC104406
0.5205 Remote Similarity NPC285623
0.5156 Remote Similarity NPC100971
0.5156 Remote Similarity NPC294409
0.5156 Remote Similarity NPC490701
0.5156 Remote Similarity NPC610981
0.5135 Remote Similarity NPC223701
0.5135 Remote Similarity NPC472583
0.5128 Remote Similarity NPC479401
0.5082 Remote Similarity NPC182428

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC12175 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