Natural Product: NPC130193

Natural Product IDNPC130193
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1E,4Z,6E)-5-Hydroxy-1,7-Bis(4-Hydroxyphenyl)Hepta-1,4,6-Trien-3-One
IUPAC Name (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-1,4,6-trien-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL131770
PubChem CID 5324473
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids
          • [CHEMONTID:0000356] Curcuminoids

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 YXAKCQIIROBKOP-HSSGTREWSA-N
Standard InCHI InChI=1S/C19H16O4/c20-16-7-1-14(2-8-16)5-11-18(22)13-19(23)12-6-15-3-9-17(21)10-4-15/h1-13,20-22H/b11-5+,12-6+,18-13-
SMILES O/C(=CC(=O)/C=C/c1ccc(cc1)O)/C=C/c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   308.1 Volume:   328.864
?
Van der Waals volume.
Dense:   0.937 LogP:   2.796
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.766
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.544
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   16.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.445 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.517 Fsp3:   0.0
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.999 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.088
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.455
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.975 Promiscuous compounds:   0.452

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.91 MDCK Permeability:   -4.769
Pgp-inhibitor:   0.061 Pgp-substrate:   0.0
PAMPA:   0.703
?
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%):   0.992 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   97.603% Volume Distribution (VD):   -0.516
Fu: 1.931%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.053
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.008 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.147
CYP2C9-inhibitor:   0.037 CYP2C9-substrate:   0.634
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.07
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.827
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.324
?
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):  8.059 Half-life (T1/2):  1.039

ADMET: Toxicity

hERG Blockers:  0.163 hERG Blockers (10um):  0.125
Human Hepatotoxicity (H-HT):  0.725 Drug-induced Liver Injury (DILI):  0.828
AMES Toxicity:  0.382 Rat Oral Acute Toxicity:  0.157
Maximum Recommended Daily Dose:  0.806 Skin Sensitization:  0.94
Carcinogencity:  0.351 Eye Corrosion:  0.009
Eye Irritation:  0.988 Respiratory Toxicity:  0.583
Drug-induced Neurotoxicity:  0.577 Ototoxicity:  0.378
Hematotoxicity:  0.06 Drug-induced Nephrotoxicity:  0.526
Genotoxicity:  0.943 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.153 Hek293 Cytotoxicity:  0.692
BCF:   1.307
?
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:   4.089
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.701
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.505
?
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
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[12350137]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota rhizome n.a. n.a. PMID[12617587]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[19615910]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[23153397]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[23738470]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. root n.a. PMID[23738470]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. leaf n.a. PMID[23901173]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[25275213]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[28068085]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota Radix n.a. n.a. PMID[29236488]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[29323912]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[731398]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9584408]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9868158]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizome Essent. Oil n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25209 Curcuma aromatica Species Zingiberaceae 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
NPT226 Individual protein Beta-2 adrenergic receptor Homo sapiens Potency n.a. 25929.0 nM PubChem BioAssay data set
NPT1005 Individual protein Tumor susceptibility gene 101 protein Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT2971 Individual protein DNA dC->dU-editing enzyme APOBEC-3F Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 25929.0 nM PubChem BioAssay data set
NPT100 Individual protein Glutaminase kidney isoform, mitochondrial Homo sapiens Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 29092.9 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT1417 Individual protein Transcriptional regulator ERG Homo sapiens Potency n.a. 3548.1 nM PubChem BioAssay data set
NPT161 Individual protein Rap guanine nucleotide exchange factor 4 Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT161 Individual protein Rap guanine nucleotide exchange factor 4 Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT4252 Individual protein Toll-like receptor 9 Homo sapiens IC50 = 9767.0 nM PubChem BioAssay data set
NPT477 Individual protein DNA dC->dU-editing enzyme APOBEC-3G Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT740 Individual protein Beta-secretase 1 Homo sapiens Inhibition = 9.0 % PMID[24360557]
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT831 Individual protein Serine/threonine-protein kinase PLK1 Homo sapiens Potency n.a. 2667.9 nM PubChem BioAssay data set
NPT740 Individual protein Beta-secretase 1 Homo sapiens IC50 = 2540.0 nM PMID[26696252]
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IC50 = 8390.0 nM PMID[26696252]
NPT4253 Individual protein Beta Lactamase Pseudomonas aeruginosa IC50 = 5133.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1161 Cell line CHO Cricetulus griseus IC50 = 40050.0 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 4147.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency = 8199.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 15848.9 nM PubChem BioAssay data set

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 NPC130193 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
0.7447 Intermediate Similarity NPC189844
0.6596 Remote Similarity NPC109083
0.6304 Remote Similarity NPC70843
0.6053 Remote Similarity NPC181709
0.5849 Remote Similarity NPC269843
0.5814 Remote Similarity NPC201967
0.5814 Remote Similarity NPC52087
0.575 Remote Similarity NPC68269
0.5745 Remote Similarity NPC280001
0.5303 Remote Similarity NPC478442
0.5208 Remote Similarity NPC14007
0.5179 Remote Similarity NPC90128
0.5111 Remote Similarity NPC51698

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC130193 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