Natural Product: NPC73503

Natural Product IDNPC73503
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QKQLSQLKXBHUSO-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 242589
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 QKQLSQLKXBHUSO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O4/c1-20-13-10-15(19)17(16(11-13)21-2)14(18)9-8-12-6-4-3-5-7-12/h3-11,19H,1-2H3
SMILES COc1cc(c(C(=O)C=Cc2ccccc2)c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.1 Volume:   299.545
?
Van der Waals volume.
Dense:   0.948 LogP:   3.238
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.312
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.83
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.676 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.004 Fsp3:   0.118
MCE-18:   12.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.919 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.555
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.916
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.685 Promiscuous compounds:   0.244

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.844 MDCK Permeability:   -4.8
Pgp-inhibitor:   0.957 Pgp-substrate:   0.009
PAMPA:   0.008
?
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):   0.014
20% Bioavailability (F20%):   0.015 30% Bioavailability (F30%):   0.145
50% Bioavailability (F50%):   0.679

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.422 MRP1:   0.258
Plasma Protein Binding (PPB):   98.175% Volume Distribution (VD):   0.127
Fu: 1.44%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.811
BSEP inhibitor:   0.953

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.115 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.943
CYP2D6-inhibitor:   0.99 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.986
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.374
?
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):  6.998 Half-life (T1/2):  0.623

ADMET: Toxicity

hERG Blockers:  0.272 hERG Blockers (10um):  0.591
Human Hepatotoxicity (H-HT):  0.548 Drug-induced Liver Injury (DILI):  0.31
AMES Toxicity:  0.557 Rat Oral Acute Toxicity:  0.17
Maximum Recommended Daily Dose:  0.354 Skin Sensitization:  0.915
Carcinogencity:  0.159 Eye Corrosion:  0.043
Eye Irritation:  0.975 Respiratory Toxicity:  0.66
Drug-induced Neurotoxicity:  0.713 Ototoxicity:  0.295
Hematotoxicity:  0.185 Drug-induced Nephrotoxicity:  0.446
Genotoxicity:  0.078 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.383 Hek293 Cytotoxicity:  0.419
BCF:   1.631
?
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:   4.215
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.489
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.937
?
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
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]
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]
NPO24672 Helleborus purpurascens Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25557 Alternaria porri Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16885 Phonus arborescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25321 Acantholimon glumaceum Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5676 Annulohypoxylon multiforme Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28771 Clematis delavayi Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24735 Cupania latifolia Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24591 Trichosanthes dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19721 Impatiens roylei Species Balsaminaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8943 Juniperus californica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22637 Kunzea ambigua Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17249 Lespedeza capitata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25410 Manilkara bidentata Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24821 Nidorella resedifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25128 Panax vietnamensis Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10407 Petromyzon marinus Species Petromyzontidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24549 Scutellaria cordifrons 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]
NPO23489 Stachys anisochila Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25468 Tabernaemontana amygdalifolia Species Apocynaceae 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]
NPO24672 Helleborus purpurascens Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18950 Cephalotaxus fortunei Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16885 Phonus arborescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28771 Clematis delavayi Species Ranunculaceae 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]
NPO24672 Helleborus purpurascens Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25468 Tabernaemontana amygdalifolia Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19721 Impatiens roylei Species Balsaminaceae 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]
NPO25410 Manilkara bidentata Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5676 Annulohypoxylon multiforme Species Xylariaceae 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

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 NPC73503 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
1.0 High Similarity NPC188646
0.8372 Intermediate Similarity NPC242294
0.8043 Intermediate Similarity NPC473391
0.8 Intermediate Similarity NPC263670
0.7872 Intermediate Similarity NPC472364
0.7674 Intermediate Similarity NPC212631
0.7674 Intermediate Similarity NPC608685
0.7447 Intermediate Similarity NPC476333
0.7447 Intermediate Similarity NPC175098
0.7447 Intermediate Similarity NPC471417
0.7447 Intermediate Similarity NPC337373
0.7347 Intermediate Similarity NPC472368
0.7234 Intermediate Similarity NPC87231
0.7083 Intermediate Similarity NPC472366
0.7 Intermediate Similarity NPC472367
0.6957 Remote Similarity NPC64359
0.6875 Remote Similarity NPC92722
0.68 Remote Similarity NPC119663
0.6735 Remote Similarity NPC150399
0.6604 Remote Similarity NPC606423
0.66 Remote Similarity NPC472365
0.62 Remote Similarity NPC56031
0.6 Remote Similarity NPC131451
0.6 Remote Similarity NPC11561
0.6 Remote Similarity NPC308037
0.6 Remote Similarity NPC265045
0.5882 Remote Similarity NPC156092
0.5882 Remote Similarity NPC15329
0.5882 Remote Similarity NPC129132
0.587 Remote Similarity NPC45438
0.5833 Remote Similarity NPC139813
0.5686 Remote Similarity NPC477243
0.56 Remote Similarity NPC336114
0.5581 Remote Similarity NPC305518
0.5577 Remote Similarity NPC119660
0.5532 Remote Similarity NPC58229
0.549 Remote Similarity NPC205468
0.5455 Remote Similarity NPC240593
0.5385 Remote Similarity NPC312318
0.5385 Remote Similarity NPC28753
0.5385 Remote Similarity NPC142165
0.5283 Remote Similarity NPC93034
0.5208 Remote Similarity NPC211120
0.5185 Remote Similarity NPC102003
0.5172 Remote Similarity NPC25287
0.5172 Remote Similarity NPC284080
0.5102 Remote Similarity NPC176930
0.5102 Remote Similarity NPC602047
0.5098 Remote Similarity NPC192304
0.5094 Remote Similarity NPC284556
0.5082 Remote Similarity NPC488391
0.5077 Remote Similarity NPC78492
0.5077 Remote Similarity NPC91288
0.5077 Remote Similarity NPC208152

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC73503 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