Natural Product: NPC201451

Natural Product IDNPC201451
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Prudomestin
IUPAC Name 3,5,7-trihydroxy-8-methoxy-2-(4-methoxyphenyl)chromen-4-one
Synonyms Prudomestin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL478812
PubChem CID 10404353
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 HLSIOUXODPWHFI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O7/c1-22-9-5-3-8(4-6-9)15-14(21)13(20)12-10(18)7-11(19)16(23-2)17(12)24-15/h3-7,18-19,21H,1-2H3
SMILES COc1ccc(cc1)c1c(c(=O)c2c(cc(c(c2o1)OC)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   2.3
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.292
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.109
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   109.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.677 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.441 Fsp3:   0.118
MCE-18:   19.0
?
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:   0.601 Fluc inhibitor:   0.554
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.869
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.539
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.393 Promiscuous compounds:   0.888

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.304 MDCK Permeability:   -4.828
Pgp-inhibitor:   0.737 Pgp-substrate:   0.151
PAMPA:   0.327
?
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):   0.156
20% Bioavailability (F20%):   0.114 30% Bioavailability (F30%):   0.655
50% Bioavailability (F50%):   0.939

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.909
Plasma Protein Binding (PPB):   97.961% Volume Distribution (VD):   -0.646
Fu: 1.54%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.848
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.971
BSEP inhibitor:   0.907

ADMET: Metabolism

CYP1A2-inhibitor:   0.37 CYP1A2-substrate:   0.371
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.813
CYP2C9-inhibitor:   0.936 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.99 CYP2D6-substrate:   0.356
CYP3A4-inhibitor:   0.068 CYP3A4-substrate:   0.012
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
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):  3.225 Half-life (T1/2):  1.489

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.432
Human Hepatotoxicity (H-HT):  0.396 Drug-induced Liver Injury (DILI):  0.891
AMES Toxicity:  0.61 Rat Oral Acute Toxicity:  0.444
Maximum Recommended Daily Dose:  0.504 Skin Sensitization:  0.382
Carcinogencity:  0.669 Eye Corrosion:  0.148
Eye Irritation:  0.978 Respiratory Toxicity:  0.849
Drug-induced Neurotoxicity:  0.093 Ototoxicity:  0.147
Hematotoxicity:  0.238 Drug-induced Nephrotoxicity:  0.171
Genotoxicity:  0.575 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.283 Hek293 Cytotoxicity:  0.398
BCF:   1.018
?
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:   3.876
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.53
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.096
?
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
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota fruit Lanyu Island, Taitung County, Taiwan n.a. PMID[10395498]
NPO25128 Panax vietnamensis Species Araliaceae Eukaryota n.a. Vietnamese n.a. PMID[11325227]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[12542368]
NPO22637 Kunzea ambigua Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[15043420]
NPO10407 Petromyzon marinus Species Petromyzontidae Eukaryota n.a. n.a. n.a. PMID[15193266]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[17822293]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[28139925]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[31184894]
NPO14951 Zanthoxylum acanthopodium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[36014481]
NPO14951 Zanthoxylum acanthopodium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[37471031]
NPO19721 Impatiens roylei Species Balsaminaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24735 Cupania latifolia Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24672 Helleborus purpurascens Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28771 Clematis delavayi Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5676 Annulohypoxylon multiforme Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25321 Acantholimon glumaceum Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16885 Phonus arborescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25557 Alternaria porri Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22637 Kunzea ambigua Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16988 Pseudodistoma novaezelandiae Species Pseudodistomidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14951 Zanthoxylum acanthopodium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24591 Trichosanthes dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25468 Tabernaemontana amygdalifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23489 Stachys anisochila Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24866 Smilax aspera Species Smilacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24549 Scutellaria cordifrons Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10407 Petromyzon marinus Species Petromyzontidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25128 Panax vietnamensis Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24821 Nidorella resedifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25410 Manilkara bidentata Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17249 Lespedeza capitata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8943 Juniperus californica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24672 Helleborus purpurascens Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14951 Zanthoxylum acanthopodium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7142 Corydalis suaveolens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14951 Zanthoxylum acanthopodium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24672 Helleborus purpurascens Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7142 Corydalis suaveolens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7142 Corydalis suaveolens Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19721 Impatiens roylei Species Balsaminaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24821 Nidorella resedifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25128 Panax vietnamensis Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24591 Trichosanthes dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17249 Lespedeza capitata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10407 Petromyzon marinus Species Petromyzontidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24866 Smilax aspera Species Smilacaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24549 Scutellaria cordifrons Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24735 Cupania latifolia Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16885 Phonus arborescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25468 Tabernaemontana amygdalifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5676 Annulohypoxylon multiforme Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23489 Stachys anisochila Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22637 Kunzea ambigua Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8943 Juniperus californica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25321 Acantholimon glumaceum Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25557 Alternaria porri Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14951 Zanthoxylum acanthopodium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25410 Manilkara bidentata Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16988 Pseudodistoma novaezelandiae Species Pseudodistomidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24672 Helleborus purpurascens Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28771 Clematis delavayi Species Ranunculaceae 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
NPT177 Tissue Aorta Rattus norvegicus Activity = 36.7 % PMID[10395498]
NPT177 Tissue Aorta Rattus norvegicus Activity = 20.0 % PMID[10395498]
NPT177 Tissue Aorta Rattus norvegicus Activity = 46.7 % PMID[10395498]
NPT177 Tissue Aorta Rattus norvegicus Activity = 83.4 % PMID[10395498]
NPT177 Tissue Aorta Rattus norvegicus Activity = 100.6 % PMID[10395498]
NPT177 Tissue Aorta Rattus norvegicus Activity = 97.8 % PMID[10395498]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 87.5 % PMID[10395498]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.0 % PMID[10395498]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 58.1 % PMID[10395498]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 73.3 % PMID[10395498]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 64.5 % PMID[10395498]

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 NPC201451 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
0.7273 Intermediate Similarity NPC610401
0.7222 Intermediate Similarity NPC86485
0.7037 Intermediate Similarity NPC241838
0.6852 Remote Similarity NPC600177
0.6545 Remote Similarity NPC44079
0.6333 Remote Similarity NPC607815
0.6129 Remote Similarity NPC273538
0.6034 Remote Similarity NPC49824
0.5932 Remote Similarity NPC54394
0.5862 Remote Similarity NPC301123
0.5672 Remote Similarity NPC605541
0.5667 Remote Similarity NPC200740
0.5667 Remote Similarity NPC159103
0.5593 Remote Similarity NPC276905
0.5593 Remote Similarity NPC281207
0.5593 Remote Similarity NPC605146
0.5574 Remote Similarity NPC189179
0.5517 Remote Similarity NPC131624
0.5517 Remote Similarity NPC245546
0.5424 Remote Similarity NPC301323
0.5424 Remote Similarity NPC152042
0.541 Remote Similarity NPC166753
0.5333 Remote Similarity NPC50403
0.5333 Remote Similarity NPC59951
0.5333 Remote Similarity NPC231772
0.5333 Remote Similarity NPC143799
0.5333 Remote Similarity NPC176665
0.5333 Remote Similarity NPC188203
0.5333 Remote Similarity NPC608038
0.5323 Remote Similarity NPC224137
0.5254 Remote Similarity NPC26227
0.5238 Remote Similarity NPC125062
0.5231 Remote Similarity NPC259411
0.5167 Remote Similarity NPC274327
0.5167 Remote Similarity NPC219330
0.5161 Remote Similarity NPC253634
0.5147 Remote Similarity NPC606048
0.5082 Remote Similarity NPC87125
0.5082 Remote Similarity NPC28274
0.5079 Remote Similarity NPC93376
0.5079 Remote Similarity NPC609179

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC201451 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
0.6129 Remote Similarity NPD4378 Phase 3

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