Natural Product: NPC470087

Natural Product IDNPC470087
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Xanthoangelol D
IUPAC Name (E)-1-[2-hydroxy-3-(2-hydroxy-3-methylbut-3-enyl)-4-methoxyphenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
Synonyms Xanthoangelol D
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1711961
PubChem CID 11302670
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003509] 3-prenylated chalcones

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 YSOKENZJQWPLRA-UXBLZVDNSA-N
Standard InCHI InChI=1S/C21H22O5/c1-13(2)19(24)12-17-20(26-3)11-9-16(21(17)25)18(23)10-6-14-4-7-15(22)8-5-14/h4-11,19,22,24-25H,1,12H2,2-3H3/b10-6+
SMILES CC(=C)C(CC1=C(C=CC(=C1O)C(=O)C=CC2=CC=C(C=C2)O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   374.882
?
Van der Waals volume.
Dense:   0.945 LogP:   3.266
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.176
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.659
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   15.0
TPSA:   86.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.402 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.04 Fsp3:   0.19
MCE-18:   30.0
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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:   0.823 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.517
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.604
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.408 Promiscuous compounds:   0.107

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.087 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.001 Pgp-substrate:   0.005
PAMPA:   0.686
?
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):   0.006
20% Bioavailability (F20%):   0.318 30% Bioavailability (F30%):   0.709
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.516
Plasma Protein Binding (PPB):   95.893% Volume Distribution (VD):   0.264
Fu: 3.241%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.957
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.187
BSEP inhibitor:   0.565

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.946
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.723
CYP2C9-inhibitor:   0.1 CYP2C9-substrate:   0.03
CYP2D6-inhibitor:   0.943 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.254
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.593
?
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):  9.398 Half-life (T1/2):  1.164

ADMET: Toxicity

hERG Blockers:  0.206 hERG Blockers (10um):  0.57
Human Hepatotoxicity (H-HT):  0.434 Drug-induced Liver Injury (DILI):  0.051
AMES Toxicity:  0.342 Rat Oral Acute Toxicity:  0.119
Maximum Recommended Daily Dose:  0.564 Skin Sensitization:  0.889
Carcinogencity:  0.246 Eye Corrosion:  0.005
Eye Irritation:  0.969 Respiratory Toxicity:  0.563
Drug-induced Neurotoxicity:  0.685 Ototoxicity:  0.701
Hematotoxicity:  0.052 Drug-induced Nephrotoxicity:  0.238
Genotoxicity:  0.183 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.157 Hek293 Cytotoxicity:  0.407
BCF:   1.296
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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:   4.185
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.374
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.961
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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
NPO21056 Angelica keiskei Species Apiaceae Eukaryota exudates n.a. n.a. PMID[16441065]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota stems n.a. n.a. PMID[18558745]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21824777]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota stems n.a. n.a. PMID[25891102]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21056 Angelica keiskei Species Apiaceae 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
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency n.a. 35481.3 nM PMID[15922595]
NPT2228 Individual protein Neuraminidase Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza Avirus (strain A/South Carolina/1/1918 H1N1)) IC50 = 12300.0 nM PMID[19817445]
NPT2228 Individual protein Neuraminidase Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza Avirus (strain A/South Carolina/1/1918 H1N1)) Ki = 14000.0 nM PMID[19674905]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 16360.1 nM Open TG-GATES in vivo data: Biochemistry
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 7943.3 nM PMID[19653667]
NPT160 Individual protein TAR DNA-binding protein 43 Homo sapiens Potency n.a. 35481.3 nM PMID[17629327]
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 31622.8 nM PMID[19534533]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 3.97 ug.mL-1 PMID[22998443]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 96.76 % PMID[15620241]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 112.2 nM PMID[20805391]
NPT2 Others Unspecified n.a. Potency n.a. 8912.5 nM PMID[12350140]
NPT2 Others Unspecified n.a. Potency n.a. 7079.5 nM DOI[10.6019/CHEMBL1201861]

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 NPC470087 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
0.7368 Intermediate Similarity NPC472419
0.7321 Intermediate Similarity NPC168105
0.7119 Intermediate Similarity NPC470089
0.7031 Intermediate Similarity NPC470211
0.678 Remote Similarity NPC483639
0.6552 Remote Similarity NPC213485
0.6452 Remote Similarity NPC321980
0.6406 Remote Similarity NPC274109
0.6129 Remote Similarity NPC144499
0.6032 Remote Similarity NPC263384
0.5652 Remote Similarity NPC474744
0.5645 Remote Similarity NPC156590
0.5614 Remote Similarity NPC205468
0.5484 Remote Similarity NPC481727
0.5484 Remote Similarity NPC481726
0.5439 Remote Similarity NPC257756
0.5397 Remote Similarity NPC269694
0.5397 Remote Similarity NPC66349
0.5397 Remote Similarity NPC41461
0.5373 Remote Similarity NPC316769
0.5373 Remote Similarity NPC484873
0.5263 Remote Similarity NPC192304
0.5263 Remote Similarity NPC23817
0.5254 Remote Similarity NPC312318
0.5254 Remote Similarity NPC477243
0.5172 Remote Similarity NPC336114
0.5147 Remote Similarity NPC486094
0.5077 Remote Similarity NPC317119
0.5075 Remote Similarity NPC21350
0.5072 Remote Similarity NPC483636
0.507 Remote Similarity NPC474772

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470087 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