Natural Product: NPC477242

Natural Product IDNPC477242
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-2',4,4'-Trihydroxy-3'-[(2E)-3,7-dimethyl-2,6-octadienyl]-6'-methoxychalcone
IUPAC Name (E)-1-[3-[(2E)-3,7-dimethylocta-2,6-dienyl]-2,4-dihydroxy-6-methoxyphenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
Synonyms 3'-geranyl-6'-O-methylchalconaringenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 24971180
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 KVLODOJZOXFBNP-PVKHHADTSA-N
Standard InCHI InChI=1S/C26H30O5/c1-17(2)6-5-7-18(3)8-14-21-23(29)16-24(31-4)25(26(21)30)22(28)15-11-19-9-12-20(27)13-10-19/h6,8-13,15-16,27,29-30H,5,7,14H2,1-4H3/b15-11+,18-8+
SMILES CC(=CCC/C(=C/CC1=C(C(=C(C=C1O)OC)C(=O)/C=C/C2=CC=C(C=C2)O)O)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.21 Volume:   458.726
?
Van der Waals volume.
Dense:   0.92 LogP:   5.924
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.083
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.573
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   16.0
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:   0.264 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.839 Fsp3:   0.269
MCE-18:   16.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   1.0 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.564
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.834
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.586 Promiscuous compounds:   0.166

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.095 MDCK Permeability:   -4.81
Pgp-inhibitor:   0.996 Pgp-substrate:   0.0
PAMPA:   0.005
?
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):   0.001
20% Bioavailability (F20%):   0.624 30% Bioavailability (F30%):   0.795
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.024
Plasma Protein Binding (PPB):   97.448% Volume Distribution (VD):   0.209
Fu: 2.51%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.325
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.703 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.906
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.992
?
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):  6.708 Half-life (T1/2):  0.88

ADMET: Toxicity

hERG Blockers:  0.204 hERG Blockers (10um):  0.628
Human Hepatotoxicity (H-HT):  0.779 Drug-induced Liver Injury (DILI):  0.652
AMES Toxicity:  0.185 Rat Oral Acute Toxicity:  0.293
Maximum Recommended Daily Dose:  0.561 Skin Sensitization:  0.972
Carcinogencity:  0.203 Eye Corrosion:  0.001
Eye Irritation:  0.896 Respiratory Toxicity:  0.919
Drug-induced Neurotoxicity:  0.547 Ototoxicity:  0.414
Hematotoxicity:  0.217 Drug-induced Nephrotoxicity:  0.399
Genotoxicity:  0.763 RPMI-8226 Immunitoxicity:  0.146
A549 Cytotoxicity:  0.473 Hek293 Cytotoxicity:  0.739
BCF:   1.84
?
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:   5.278
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.824
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.293
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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
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 = 8200 nM PMID[18611049]
NPT2 Others Unspecified n.a. Activity = 3.4 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 NPC477242 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
0.8276 Intermediate Similarity NPC249606
0.7031 Intermediate Similarity NPC23126
0.6935 Remote Similarity NPC25287
0.6875 Remote Similarity NPC266689
0.6875 Remote Similarity NPC21350
0.6716 Remote Similarity NPC274109
0.6571 Remote Similarity NPC228504
0.6515 Remote Similarity NPC321980
0.6418 Remote Similarity NPC316769
0.6389 Remote Similarity NPC262039
0.6061 Remote Similarity NPC1486
0.6 Remote Similarity NPC66349
0.6 Remote Similarity NPC41461
0.5942 Remote Similarity NPC264112
0.5909 Remote Similarity NPC317119
0.5867 Remote Similarity NPC488435
0.5844 Remote Similarity NPC195796
0.5833 Remote Similarity NPC153979
0.5811 Remote Similarity NPC64915
0.5811 Remote Similarity NPC213896
0.5758 Remote Similarity NPC269694
0.5735 Remote Similarity NPC13575
0.5696 Remote Similarity NPC287328
0.5658 Remote Similarity NPC22192
0.5658 Remote Similarity NPC185276
0.56 Remote Similarity NPC483812
0.5584 Remote Similarity NPC226025
0.5584 Remote Similarity NPC278778
0.5571 Remote Similarity NPC166138
0.5556 Remote Similarity NPC129132
0.5556 Remote Similarity NPC470210
0.5541 Remote Similarity NPC152233
0.5538 Remote Similarity NPC98254
0.5526 Remote Similarity NPC470328
0.5526 Remote Similarity NPC209614
0.5526 Remote Similarity NPC164272
0.5526 Remote Similarity NPC470327
0.5467 Remote Similarity NPC290133
0.5443 Remote Similarity NPC282009
0.5441 Remote Similarity NPC477244
0.5429 Remote Similarity NPC483966
0.5397 Remote Similarity NPC477243
0.5385 Remote Similarity NPC72158
0.5385 Remote Similarity NPC470326
0.5352 Remote Similarity NPC488391
0.5342 Remote Similarity NPC475042
0.5312 Remote Similarity NPC119660
0.5312 Remote Similarity NPC263670
0.5294 Remote Similarity NPC168105
0.5263 Remote Similarity NPC470211
0.525 Remote Similarity NPC45849
0.525 Remote Similarity NPC472626
0.525 Remote Similarity NPC210459
0.5238 Remote Similarity NPC91105
0.5224 Remote Similarity NPC166995
0.5211 Remote Similarity NPC263384
0.5205 Remote Similarity NPC294387
0.5195 Remote Similarity NPC43345
0.5152 Remote Similarity NPC65761
0.5143 Remote Similarity NPC226636
0.5128 Remote Similarity NPC488556
0.5125 Remote Similarity NPC472628
0.5075 Remote Similarity NPC472029
0.5072 Remote Similarity NPC482939
0.5063 Remote Similarity NPC472627
0.5063 Remote Similarity NPC58805

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477242 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