Natural Product: NPC540174

Natural Product IDNPC540174
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Morelosin
IUPAC Name 2-(3,5-dimethoxyphenyl)-3,5,7-trihydroxy-chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 HEJAFZFLVQINJF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O7/c1-22-10-3-8(4-11(7-10)23-2)17-16(21)15(20)14-12(19)5-9(18)6-13(14)24-17/h3-7,18-19,21H,1-2H3
SMILES COC1=CC(OC)=CC(C2=C(O)C(=O)C3=C(O)C=C(O)C=C3O2)=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   2.541
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.527
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.277
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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:   2.455 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:   0.69 Fluc inhibitor:   0.571
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.881
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.642
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.413 Promiscuous compounds:   0.943

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.283 MDCK Permeability:   -4.843
Pgp-inhibitor:   0.98 Pgp-substrate:   0.058
PAMPA:   0.013
?
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):   0.409
20% Bioavailability (F20%):   0.01 30% Bioavailability (F30%):   0.604
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.298
Plasma Protein Binding (PPB):   98.03% Volume Distribution (VD):   -0.57
Fu: 1.31%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.974

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.978
CYP2C19-inhibitor:   0.913 CYP2C19-substrate:   0.99
CYP2C9-inhibitor:   0.913 CYP2C9-substrate:   0.753
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  4.733 Half-life (T1/2):  1.079

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.452
Human Hepatotoxicity (H-HT):  0.461 Drug-induced Liver Injury (DILI):  0.737
AMES Toxicity:  0.578 Rat Oral Acute Toxicity:  0.481
Maximum Recommended Daily Dose:  0.77 Skin Sensitization:  0.406
Carcinogencity:  0.738 Eye Corrosion:  0.496
Eye Irritation:  0.994 Respiratory Toxicity:  0.769
Drug-induced Neurotoxicity:  0.088 Ototoxicity:  0.118
Hematotoxicity:  0.137 Drug-induced Nephrotoxicity:  0.07
Genotoxicity:  0.905 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.543
BCF:   1.043
?
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:   3.841
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.363
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.942
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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
NPO29365 Baileya multiradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29365 Baileya multiradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29365 Baileya multiradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29365 Baileya multiradiata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29365 Baileya multiradiata Species Asteraceae 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 NPC540174 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
0.82 Intermediate Similarity NPC219330
0.8039 Intermediate Similarity NPC28274
0.7692 Intermediate Similarity NPC241838
0.7407 Intermediate Similarity NPC159103
0.7358 Intermediate Similarity NPC50403
0.7273 Intermediate Similarity NPC609179
0.7143 Intermediate Similarity NPC133953
0.7143 Intermediate Similarity NPC125062
0.7091 Intermediate Similarity NPC54394
0.7037 Intermediate Similarity NPC483773
0.6604 Remote Similarity NPC179271
0.6538 Remote Similarity NPC116775
0.6538 Remote Similarity NPC187432
0.6415 Remote Similarity NPC169749
0.6415 Remote Similarity NPC20791
0.5862 Remote Similarity NPC143799
0.5862 Remote Similarity NPC62536
0.5862 Remote Similarity NPC610359
0.5833 Remote Similarity NPC606638
0.5818 Remote Similarity NPC601197
0.5714 Remote Similarity NPC216361
0.569 Remote Similarity NPC152042
0.5667 Remote Similarity NPC166753
0.5614 Remote Similarity NPC256042
0.5593 Remote Similarity NPC59951
0.5593 Remote Similarity NPC231772
0.5593 Remote Similarity NPC87125
0.5593 Remote Similarity NPC120464
0.5593 Remote Similarity NPC605755
0.5574 Remote Similarity NPC162351
0.5574 Remote Similarity NPC12200
0.5574 Remote Similarity NPC603596
0.5484 Remote Similarity NPC252933
0.5424 Remote Similarity NPC44079
0.5424 Remote Similarity NPC123886
0.5424 Remote Similarity NPC184536
0.5424 Remote Similarity NPC103342
0.541 Remote Similarity NPC200740
0.5385 Remote Similarity NPC205046
0.5333 Remote Similarity NPC286342
0.5333 Remote Similarity NPC201451
0.5333 Remote Similarity NPC601901
0.5303 Remote Similarity NPC200694
0.5286 Remote Similarity NPC171821
0.5263 Remote Similarity NPC606270
0.5254 Remote Similarity NPC26227
0.5246 Remote Similarity NPC600900
0.5238 Remote Similarity NPC183950
0.5238 Remote Similarity NPC279989
0.5167 Remote Similarity NPC98661
0.5161 Remote Similarity NPC82325
0.5156 Remote Similarity NPC483775
0.5082 Remote Similarity NPC281207
0.5079 Remote Similarity NPC52005
0.5079 Remote Similarity NPC610401
0.5068 Remote Similarity NPC254306

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC540174 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
0.6415 Remote Similarity NPD1512 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