Natural Product: NPC477244

Natural Product IDNPC477244
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-2'-Methoxy-3'-prenyl-4,4',6'-trihydroxychalcone
IUPAC Name (E)-1-[4,6-dihydroxy-2-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 24971181
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 MFZJQZIWPCJMCW-YRNVUSSQSA-N
Standard InCHI InChI=1S/C21H22O5/c1-13(2)4-10-16-18(24)12-19(25)20(21(16)26-3)17(23)11-7-14-5-8-15(22)9-6-14/h4-9,11-12,22,24-25H,10H2,1-3H3/b11-7+
SMILES CC(=CCC1=C(C(=C(C=C1O)O)C(=O)/C=C/C2=CC=C(C=C2)O)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   374.882
?
Van der Waals volume.
Dense:   0.945 LogP:   3.76
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.477
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.392
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   86.99
?
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:   0.411 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.679 Fsp3:   0.19
MCE-18:   15.0
?
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:   0.989 Fluc inhibitor:   0.998
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.596
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.829
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.571 Promiscuous compounds:   0.17

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.064 MDCK Permeability:   -4.842
Pgp-inhibitor:   0.876 Pgp-substrate:   0.001
PAMPA:   0.039
?
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):   0.003
20% Bioavailability (F20%):   0.983 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.054
Plasma Protein Binding (PPB):   96.379% Volume Distribution (VD):   0.292
Fu: 3.137%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.953
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.14 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.678 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  7.249 Half-life (T1/2):  1.003

ADMET: Toxicity

hERG Blockers:  0.126 hERG Blockers (10um):  0.569
Human Hepatotoxicity (H-HT):  0.589 Drug-induced Liver Injury (DILI):  0.42
AMES Toxicity:  0.46 Rat Oral Acute Toxicity:  0.385
Maximum Recommended Daily Dose:  0.582 Skin Sensitization:  0.939
Carcinogencity:  0.17 Eye Corrosion:  0.001
Eye Irritation:  0.929 Respiratory Toxicity:  0.894
Drug-induced Neurotoxicity:  0.648 Ototoxicity:  0.325
Hematotoxicity:  0.113 Drug-induced Nephrotoxicity:  0.552
Genotoxicity:  0.783 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.48 Hek293 Cytotoxicity:  0.788
BCF:   1.684
?
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:   4.744
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.003
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.505
?
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
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[10336650]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[15679315]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[16252923]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[17624889]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18611049]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18768384]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[19476340]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[21912858]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[22111577]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. flower n.a. PMID[22166201]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[23790907]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[24948953]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[25564559]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[29154541]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[30384263]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[37631012]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[38354824]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[39199155]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13879 Humulus lupulus Species Cannabaceae 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
NPT165 Cell line HeLa Homo sapiens IC50 = 10400 nM PMID[18611049]
NPT2 Others Unspecified n.a. Activity = 5.2 n.a. PMID[18611049]

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 NPC477244 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
0.7321 Intermediate Similarity NPC1486
0.6964 Remote Similarity NPC41461
0.6735 Remote Similarity NPC28918
0.6667 Remote Similarity NPC66349
0.6441 Remote Similarity NPC249606
0.6379 Remote Similarity NPC168105
0.6271 Remote Similarity NPC27643
0.6182 Remote Similarity NPC129132
0.6102 Remote Similarity NPC269694
0.6 Remote Similarity NPC131039
0.5965 Remote Similarity NPC30501
0.5862 Remote Similarity NPC98254
0.5806 Remote Similarity NPC107572
0.5806 Remote Similarity NPC32739
0.5714 Remote Similarity NPC262038
0.5714 Remote Similarity NPC319910
0.5625 Remote Similarity NPC166138
0.5614 Remote Similarity NPC119660
0.5614 Remote Similarity NPC263670
0.5574 Remote Similarity NPC482939
0.5517 Remote Similarity NPC186838
0.5469 Remote Similarity NPC263384
0.5469 Remote Similarity NPC21350
0.5441 Remote Similarity NPC477242
0.5439 Remote Similarity NPC477243
0.5424 Remote Similarity NPC72158
0.5397 Remote Similarity NPC105213
0.5373 Remote Similarity NPC274109
0.5352 Remote Similarity NPC488270
0.5352 Remote Similarity NPC488271
0.5312 Remote Similarity NPC324436
0.5312 Remote Similarity NPC78
0.5303 Remote Similarity NPC316769
0.5263 Remote Similarity NPC205468
0.5246 Remote Similarity NPC169250
0.5238 Remote Similarity NPC25287
0.5238 Remote Similarity NPC317119
0.5179 Remote Similarity NPC192304
0.5167 Remote Similarity NPC190043
0.5156 Remote Similarity NPC226636
0.5156 Remote Similarity NPC472419
0.5152 Remote Similarity NPC106985
0.5152 Remote Similarity NPC321980
0.5152 Remote Similarity NPC482763
0.5143 Remote Similarity NPC166934
0.5088 Remote Similarity NPC257756
0.5088 Remote Similarity NPC336114
0.5085 Remote Similarity NPC98115
0.5085 Remote Similarity NPC87231
0.5085 Remote Similarity NPC56031
0.5082 Remote Similarity NPC103356

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477244 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