Natural Product: NPC260952

Natural Product IDNPC260952
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-Cinnamyl (E)-P-Coumarate
IUPAC Name [(E)-3-phenylprop-2-enyl] (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL452208
PubChem CID 11288990
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0003002] Hydroxycinnamic acid esters
            • [CHEMONTID:0000465] Coumaric acid esters

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 JDBSEUVQZVQSCN-NJPWYCGFSA-N
Standard InCHI InChI=1S/C18H16O3/c19-17-11-8-16(9-12-17)10-13-18(20)21-14-4-7-15-5-2-1-3-6-15/h1-13,19H,14H2/b7-4+,13-10+
SMILES c1ccc(cc1)/C=C/COC(=O)/C=C/c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   280.11 Volume:   305.414
?
Van der Waals volume.
Dense:   0.917 LogP:   3.716
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.3
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.493
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   46.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.671 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.066 Fsp3:   0.056
MCE-18:   10.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.998 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.039
?
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:   0.997 Promiscuous compounds:   0.837

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.89 MDCK Permeability:   -4.691
Pgp-inhibitor:   0.95 Pgp-substrate:   0.002
PAMPA:   0.181
?
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):   0.006
20% Bioavailability (F20%):   0.909 30% Bioavailability (F30%):   0.984
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.092 MRP1:   0.023
Plasma Protein Binding (PPB):   98.988% Volume Distribution (VD):   -0.199
Fu: 0.896%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.077
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.971
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.294
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.969
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.786
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.071
?
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):  11.483 Half-life (T1/2):  0.707

ADMET: Toxicity

hERG Blockers:  0.406 hERG Blockers (10um):  0.691
Human Hepatotoxicity (H-HT):  0.443 Drug-induced Liver Injury (DILI):  0.602
AMES Toxicity:  0.714 Rat Oral Acute Toxicity:  0.072
Maximum Recommended Daily Dose:  0.752 Skin Sensitization:  0.961
Carcinogencity:  0.507 Eye Corrosion:  0.003
Eye Irritation:  0.889 Respiratory Toxicity:  0.138
Drug-induced Neurotoxicity:  0.657 Ototoxicity:  0.113
Hematotoxicity:  0.059 Drug-induced Nephrotoxicity:  0.22
Genotoxicity:  0.634 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.098 Hek293 Cytotoxicity:  0.754
BCF:   1.318
?
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:   4.483
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.549
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.312
?
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
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. n.a. n.a. PMID[17548953]
NPO13379 Schizanthus tricolor Species Solanaceae Eukaryota Aerial parts n.a. n.a. PMID[20166702]
NPO40884 Mexican propolis Species n.a. n.a. n.a. n.a. n.a. PMID[20307087]
NPO11266 Garcinia cambogia Species Clusiaceae Eukaryota n.a. exocarp n.a. PMID[21114277]
NPO13379 Schizanthus tricolor Species Solanaceae Eukaryota n.a. aerial part n.a. PMID[21171571]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. n.a. n.a. PMID[24675423]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. Bako, Ethiopia PMID[24926420]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. Enemore, Ethiopia PMID[24926420]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. Gedo, Ethiopia PMID[24926420]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. Holleta, Ethiopia PMID[24926420]
NPO33094 korean propolis Species n.a. n.a. n.a. n.a. n.a. PMID[24928402]
NPO3013 Clathria basilana Species Microcionidae Eukaryota n.a. n.a. n.a. PMID[29094598]
NPO14369 Pocillopora eydouxi Species Pocilloporidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40884 Mexican propolis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO33094 korean propolis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO12521 Sphaeranthus confertifolius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13379 Schizanthus tricolor Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14169 Acrocarpia paniculata Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13473 Anodendron affine Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13876 Cedrela salvadorensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3013 Clathria basilana Species Microcionidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5280 Rubia tetragona Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11266 Garcinia cambogia Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13669 Hertia cheirifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9569 Licaria chrysophylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7541 Ormosia hosiei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13178 Ornithoglossum viride Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4700 Pertusaria truncata Species Pertusariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11842 Petasites laevigatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14470 Polypodium decumanum Species Polypodiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7541 Ormosia hosiei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11842 Petasites laevigatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13473 Anodendron affine Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11266 Garcinia cambogia Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11266 Garcinia cambogia Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11842 Petasites laevigatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7541 Ormosia hosiei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13473 Anodendron affine Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7541 Ormosia hosiei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5280 Rubia tetragona Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12006 Apis mellifera Species Apidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14369 Pocillopora eydouxi Species Pocilloporidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4700 Pertusaria truncata Species Pertusariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12521 Sphaeranthus confertifolius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3013 Clathria basilana Species Microcionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11842 Petasites laevigatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14470 Polypodium decumanum Species Polypodiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14169 Acrocarpia paniculata Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13178 Ornithoglossum viride Species Colchicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13876 Cedrela salvadorensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13473 Anodendron affine Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9569 Licaria chrysophylla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13379 Schizanthus tricolor Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7541 Ormosia hosiei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13669 Hertia cheirifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11266 Garcinia cambogia Species Clusiaceae 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
NPT306 Cell line PC-3 Homo sapiens IC50 = 143000.0 nM PMID[15787433]
NPT165 Cell line HeLa Homo sapiens IC50 = 160000.0 nM PMID[15787433]
NPT81 Cell line A549 Homo sapiens IC50 = 120000.0 nM PMID[15787433]
NPT3887 Cell line CNE Homo sapiens IC50 = 162000.0 nM PMID[15787433]
NPT91 Cell line KB Homo sapiens IC50 > 100.0 ug.mL-1 PMID[15787433]
NPT461 Cell line PANC-1 Homo sapiens PC50 = 38.2 uM PMID[20307087]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100.0 ug.mL-1 PMID[15787433]
NPT2 Others Unspecified n.a. IC50 = 65000.0 nM PMID[15787433]
NPT2 Others Unspecified n.a. Ratio IC50 > 500.0 n.a. PMID[24928402]

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 NPC260952 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
0.7895 Intermediate Similarity NPC208183
0.7895 Intermediate Similarity NPC243289
0.7073 Intermediate Similarity NPC304638
0.6829 Remote Similarity NPC171843
0.6585 Remote Similarity NPC176228
0.6341 Remote Similarity NPC253746
0.6304 Remote Similarity NPC206341
0.617 Remote Similarity NPC82731
0.6122 Remote Similarity NPC277460
0.6122 Remote Similarity NPC246704
0.6098 Remote Similarity NPC167577
0.6078 Remote Similarity NPC482044
0.5854 Remote Similarity NPC175393
0.5833 Remote Similarity NPC261453
0.58 Remote Similarity NPC273741
0.58 Remote Similarity NPC608423
0.58 Remote Similarity NPC611337
0.5682 Remote Similarity NPC303245
0.549 Remote Similarity NPC263386
0.549 Remote Similarity NPC141791
0.5435 Remote Similarity NPC95381
0.5435 Remote Similarity NPC213156
0.5435 Remote Similarity NPC240108
0.5366 Remote Similarity NPC287790
0.5366 Remote Similarity NPC3672
0.5294 Remote Similarity NPC271641
0.5217 Remote Similarity NPC94343
0.5217 Remote Similarity NPC226008
0.5185 Remote Similarity NPC204466
0.5102 Remote Similarity NPC217472
0.5088 Remote Similarity NPC476872

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC260952 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