Natural Product: NPC14007

Natural Product IDNPC14007
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-(4-Hydroxy-3Methoxyphenyl)-5-(4-Hydroxyphenyl)-Penta-(1E,4E)-1,4-Dien-3One
IUPAC Name (1E,4E)-1-(4-hydroxy-3-methoxyphenyl)-5-(4-hydroxyphenyl)penta-1,4-dien-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2398585
PubChem CID 10469828
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives

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 QVRYUUYYIWAQHV-LUZURFALSA-N
Standard InCHI InChI=1S/C18H16O4/c1-22-18-12-14(6-11-17(18)21)5-10-16(20)9-4-13-2-7-15(19)8-3-13/h2-12,19,21H,1H3/b9-4+,10-5+
SMILES COc1cc(/C=C/C(=O)/C=C/c2ccc(cc2)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   296.1 Volume:   314.204
?
Van der Waals volume.
Dense:   0.942 LogP:   2.837
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.881
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.966
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   15.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.83 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.214 Fsp3:   0.056
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.995 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.289
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.726
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.932 Promiscuous compounds:   0.616

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.021 MDCK Permeability:   -4.823
Pgp-inhibitor:   0.36 Pgp-substrate:   0.002
PAMPA:   0.055
?
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):   0.01
20% Bioavailability (F20%):   0.903 30% Bioavailability (F30%):   0.944
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.018
Plasma Protein Binding (PPB):   97.579% Volume Distribution (VD):   -0.365
Fu: 1.965%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.364
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.726
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.672
CYP2C9-inhibitor:   0.25 CYP2C9-substrate:   0.136
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.588
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.006
?
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):  9.199 Half-life (T1/2):  0.979

ADMET: Toxicity

hERG Blockers:  0.293 hERG Blockers (10um):  0.475
Human Hepatotoxicity (H-HT):  0.645 Drug-induced Liver Injury (DILI):  0.412
AMES Toxicity:  0.641 Rat Oral Acute Toxicity:  0.129
Maximum Recommended Daily Dose:  0.767 Skin Sensitization:  0.972
Carcinogencity:  0.342 Eye Corrosion:  0.02
Eye Irritation:  0.968 Respiratory Toxicity:  0.581
Drug-induced Neurotoxicity:  0.609 Ototoxicity:  0.191
Hematotoxicity:  0.076 Drug-induced Nephrotoxicity:  0.215
Genotoxicity:  0.859 RPMI-8226 Immunitoxicity:  0.143
A549 Cytotoxicity:  0.298 Hek293 Cytotoxicity:  0.833
BCF:   1.226
?
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:   3.833
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.121
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.659
?
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]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[23153397]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota rhizomes n.a. n.a. PMID[23707257]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. leaf n.a. PMID[23901173]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[28068085]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9584408]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24124 Curcuma longa 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 n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Root 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 Essential Oil 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 Rhizome n.a. n.a. Database[FooDB]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14409 Dioscorea nipponica Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14409 Dioscorea nipponica Species Dioscoreaceae 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
NPT34 Cell line BV-2 Mus musculus Activity = 25.5 % PMID[23707257]
NPT34 Cell line BV-2 Mus musculus IC50 = 5990.0 nM PMID[23707257]

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 NPC14007 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
0.8947 High Similarity NPC224814
0.8333 Intermediate Similarity NPC71941
0.7708 Intermediate Similarity NPC189844
0.7381 Intermediate Similarity NPC160900
0.7174 Intermediate Similarity NPC60962
0.6875 Remote Similarity NPC109083
0.6596 Remote Similarity NPC106659
0.6596 Remote Similarity NPC66905
0.6585 Remote Similarity NPC36108
0.6585 Remote Similarity NPC233731
0.6585 Remote Similarity NPC610203
0.6512 Remote Similarity NPC39793
0.6222 Remote Similarity NPC107588
0.6222 Remote Similarity NPC137537
0.6136 Remote Similarity NPC78918
0.6136 Remote Similarity NPC139617
0.6111 Remote Similarity NPC269843
0.6078 Remote Similarity NPC110313
0.5926 Remote Similarity NPC151167
0.5918 Remote Similarity NPC310338
0.5882 Remote Similarity NPC254659
0.5854 Remote Similarity NPC246358
0.5741 Remote Similarity NPC213552
0.5741 Remote Similarity NPC304622
0.5714 Remote Similarity NPC68269
0.5714 Remote Similarity NPC202474
0.5636 Remote Similarity NPC474784
0.561 Remote Similarity NPC181709
0.5536 Remote Similarity NPC253455
0.549 Remote Similarity NPC246704
0.5472 Remote Similarity NPC204466
0.5472 Remote Similarity NPC70752
0.5439 Remote Similarity NPC90128
0.5435 Remote Similarity NPC201967
0.54 Remote Similarity NPC276014
0.537 Remote Similarity NPC15621
0.5345 Remote Similarity NPC153644
0.5319 Remote Similarity NPC10932
0.5283 Remote Similarity NPC289459
0.5273 Remote Similarity NPC276466
0.5273 Remote Similarity NPC158949
0.5263 Remote Similarity NPC195749
0.5263 Remote Similarity NPC35961
0.5246 Remote Similarity NPC471110
0.5208 Remote Similarity NPC130193
0.5192 Remote Similarity NPC281298
0.5185 Remote Similarity NPC485638
0.5172 Remote Similarity NPC271785
0.5111 Remote Similarity NPC159418
0.5106 Remote Similarity NPC71579
0.5106 Remote Similarity NPC51698
0.5102 Remote Similarity NPC70744
0.5094 Remote Similarity NPC148627
0.5091 Remote Similarity NPC83062
0.5088 Remote Similarity NPC84076
0.5085 Remote Similarity NPC299583
0.5085 Remote Similarity NPC204848
0.5085 Remote Similarity NPC485282
0.5085 Remote Similarity NPC160607
0.5085 Remote Similarity NPC41473
0.5085 Remote Similarity NPC312770
0.5085 Remote Similarity NPC485283
0.5085 Remote Similarity NPC485281

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC14007 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
0.7381 Intermediate Similarity NPD4379 Clinical (unspecified phase)

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