Natural Product: NPC286006

Natural Product IDNPC286006
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 P-Hydroxycinnamaldehyde
IUPAC Name (E)-3-(4-hydroxyphenyl)prop-2-enal
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL431836
PubChem CID 641301
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000029] Cinnamaldehydes

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 CJXMVKYNVIGQBS-OWOJBTEDSA-N
Standard InCHI InChI=1S/C9H8O2/c10-7-1-2-8-3-5-9(11)6-4-8/h1-7,11H/b2-1+
SMILES C(=Cc1ccc(cc1)O)/C=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   148.05 Volume:   160.062
?
Van der Waals volume.
Dense:   0.925 LogP:   1.803
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.673
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.369
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   8.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.511 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.167 Fsp3:   0.0
MCE-18:   5.0
?
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:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.307 Fluc inhibitor:   0.924
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.15
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.708

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.848 MDCK Permeability:   -4.772
Pgp-inhibitor:   0.44 Pgp-substrate:   0.038
PAMPA:   0.342
?
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):   0.022
20% Bioavailability (F20%):   0.773 30% Bioavailability (F30%):   0.78
50% Bioavailability (F50%):   0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.016 MRP1:   0.091
Plasma Protein Binding (PPB):   90.251% Volume Distribution (VD):   -0.414
Fu: 8.615%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.96
OATP1B3 inhibitor:   0.975 BCRP inhibitor:   0.261
BSEP inhibitor:   0.968

ADMET: Metabolism

CYP1A2-inhibitor:   0.049 CYP1A2-substrate:   0.96
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.792
CYP2C9-inhibitor:   0.284 CYP2C9-substrate:   0.526
CYP2D6-inhibitor:   0.983 CYP2D6-substrate:   0.401
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.974
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):  11.65 Half-life (T1/2):  1.119

ADMET: Toxicity

hERG Blockers:  0.203 hERG Blockers (10um):  0.466
Human Hepatotoxicity (H-HT):  0.602 Drug-induced Liver Injury (DILI):  0.169
AMES Toxicity:  0.745 Rat Oral Acute Toxicity:  0.331
Maximum Recommended Daily Dose:  0.373 Skin Sensitization:  0.944
Carcinogencity:  0.499 Eye Corrosion:  0.869
Eye Irritation:  0.997 Respiratory Toxicity:  0.492
Drug-induced Neurotoxicity:  0.821 Ototoxicity:  0.169
Hematotoxicity:  0.066 Drug-induced Nephrotoxicity:  0.286
Genotoxicity:  0.687 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.099 Hek293 Cytotoxicity:  0.235
BCF:   1.047
?
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:   3.605
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.739
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.534
?
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
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. stem wood n.a. DOI[10.1021/np100247r]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[10395501]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[10425140]
NPO2166 Ajania fruticulosa Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[10425142]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[12951092]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[12951092]
NPO6333 Annona glabra Species Annonaceae Eukaryota Fruits n.a. n.a. PMID[15568797]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[15930771]
NPO6333 Annona glabra Species Annonaceae Eukaryota stem Taipei Botanical Garden, Taipei, Taiwan, China 2006-MAR PMID[20828184]
NPO6333 Annona glabra Species Annonaceae Eukaryota fruits n.a. n.a. PMID[25499882]
NPO7252 Sonchus oleraceus Species Asteraceae Eukaryota n.a. Molise Region, Italy Autumn 2018 PMID[32803719]
NPO7252 Sonchus oleraceus Species Asteraceae Eukaryota n.a. Molise Region, Italy Spring 2019 PMID[32803719]
NPO7252 Sonchus oleraceus Species Asteraceae Eukaryota n.a. Molise Region, Italy PMID[32803719]
NPO7252 Sonchus oleraceus Species Asteraceae Eukaryota n.a The rural area of Viçosa, State of Minas Gerais (MG), Brazil Adult stage PMID[35282307]
NPO7252 Sonchus oleraceus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38931144]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[38999684]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[9584397]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[9599260]
NPO247 Urceolaria bryophila Species Trichodinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7252 Sonchus oleraceus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27645 Fructus galangae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO2166 Ajania fruticulosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8566 Astragalus curvicarpus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1715 Eucalyptus radiata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2901 Ilex taubertiana Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17850 Torreya grandis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17491 Torreya nuncifera Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27645 Fructus galangae n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27645 Fructus galangae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17850 Torreya grandis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17491 Torreya nuncifera Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7252 Sonchus oleraceus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17850 Torreya grandis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2166 Ajania fruticulosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8566 Astragalus curvicarpus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5033 Alpinia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2901 Ilex taubertiana Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1715 Eucalyptus radiata Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO247 Urceolaria bryophila Species Trichodinidae 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
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 70.79 % PMID[23571415]
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 3548.1 nM PubChem BioAssay data set
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 139.56 % PMID[23571415]
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 7079.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT521 Cell line RBL-2H3 Rattus norvegicus IC50 > 100000.0 nM PMID[12951092]
NPT521 Cell line RBL-2H3 Rattus norvegicus Inhibition = 22.0 % PMID[12951092]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 26400.0 nM PMID[33207281]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[37638616]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 8.9 % PMID[27756508]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 12.8 % PMID[27756508]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 18300.0 nM PMID[27756508]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 67.4 % PMID[27756508]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 104.5 % PMID[27756508]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus IC50 = 20000.0 nM PMID[15780639]
NPT32 Organism Mus musculus Mus musculus Activity = 102.7 % PMID[27756508]
NPT32 Organism Mus musculus Mus musculus Activity = 108.3 % PMID[27756508]
NPT32 Organism Mus musculus Mus musculus Activity = 94.3 % PMID[27756508]
NPT32 Organism Mus musculus Mus musculus Activity = 66.8 % PMID[27756508]





 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 NPC286006 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
0.7 Intermediate Similarity NPC19149
0.6552 Remote Similarity NPC239808
0.6452 Remote Similarity NPC181709
0.6429 Remote Similarity NPC248817
0.6061 Remote Similarity NPC68269
0.5882 Remote Similarity NPC253746
0.5882 Remote Similarity NPC17525
0.5862 Remote Similarity NPC169222
0.5862 Remote Similarity NPC235059
0.5862 Remote Similarity NPC16190
0.5806 Remote Similarity NPC104216
0.5676 Remote Similarity NPC39793
0.5556 Remote Similarity NPC171843
0.5405 Remote Similarity NPC304638
0.5357 Remote Similarity NPC265146
0.5294 Remote Similarity NPC184169
0.5294 Remote Similarity NPC283711
0.5263 Remote Similarity NPC19174
0.5263 Remote Similarity NPC73532
0.5263 Remote Similarity NPC201967
0.5263 Remote Similarity NPC115159
0.5263 Remote Similarity NPC51698
0.5152 Remote Similarity NPC13755
0.5143 Remote Similarity NPC32977
0.5143 Remote Similarity NPC81010

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC286006 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