Natural Product: NPC474275

Natural Product IDNPC474275
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S,5R)-2,5-Dihydroxycyclopentyl) 3-(3,4-Dihydroxyphenyl)Acrylate
IUPAC Name [(2S,5R)-2,5-dihydroxycyclopentyl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464608
PubChem CID 9903815
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0000059] Coumaric 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 XYGMVEGBGQSULF-RQEVDEIRSA-N
Standard InCHI InChI=1S/C14H16O6/c15-9-3-1-8(7-12(9)18)2-6-13(19)20-14-10(16)4-5-11(14)17/h1-3,6-7,10-11,14-18H,4-5H2/b6-2+/t10-,11+,14?
SMILES C1CC(C(C1O)OC(=O)C=CC2=CC(=C(C=C2)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   280.09 Volume:   273.146
?
Van der Waals volume.
Dense:   1.025 LogP:   1.53
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.818
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.755
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.366 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.309 Fsp3:   0.357
MCE-18:   45.842
?
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:   1
Colloidal aggregators:   0.704 Fluc inhibitor:   0.654
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.284
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.595
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.452 Promiscuous compounds:   0.975

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.908 MDCK Permeability:   -4.98
Pgp-inhibitor:   0.0 Pgp-substrate:   0.567
PAMPA:   0.998
?
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):   0.923
20% Bioavailability (F20%):   0.98 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.777
Plasma Protein Binding (PPB):   64.544% Volume Distribution (VD):   0.189
Fu: 37.174%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.344
OATP1B3 inhibitor:   0.979 BCRP inhibitor:   0.146
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.159
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.664
HLM stability:   0.001
?
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):  12.682 Half-life (T1/2):  2.37

ADMET: Toxicity

hERG Blockers:  0.171 hERG Blockers (10um):  0.694
Human Hepatotoxicity (H-HT):  0.56 Drug-induced Liver Injury (DILI):  0.234
AMES Toxicity:  0.581 Rat Oral Acute Toxicity:  0.343
Maximum Recommended Daily Dose:  0.711 Skin Sensitization:  0.966
Carcinogencity:  0.235 Eye Corrosion:  0.001
Eye Irritation:  0.491 Respiratory Toxicity:  0.242
Drug-induced Neurotoxicity:  0.165 Ototoxicity:  0.842
Hematotoxicity:  0.023 Drug-induced Nephrotoxicity:  0.208
Genotoxicity:  0.216 RPMI-8226 Immunitoxicity:  0.036
A549 Cytotoxicity:  0.5 Hek293 Cytotoxicity:  0.539
BCF:   0.536
?
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:   3.226
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.781
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.13
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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
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[9917288]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruits n.a. Database[FooDB]
NPO24693 Prunus cerasus Species Rosaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO24693 Prunus cerasus Species Rosaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 80.0 % PMID[9917288]

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 NPC474275 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
0.7778 Intermediate Similarity NPC224208
0.7778 Intermediate Similarity NPC41661
0.74 Intermediate Similarity NPC26241
0.7333 Intermediate Similarity NPC233669
0.7174 Intermediate Similarity NPC281277
0.7115 Intermediate Similarity NPC219428
0.7021 Intermediate Similarity NPC309434
0.6981 Remote Similarity NPC474875
0.6727 Remote Similarity NPC319628
0.6667 Remote Similarity NPC147192
0.6279 Remote Similarity NPC226250
0.6226 Remote Similarity NPC258469
0.6226 Remote Similarity NPC43158
0.6226 Remote Similarity NPC610147
0.6154 Remote Similarity NPC470849
0.6154 Remote Similarity NPC474895
0.5926 Remote Similarity NPC470848
0.5926 Remote Similarity NPC182217
0.5893 Remote Similarity NPC13818
0.587 Remote Similarity NPC95381
0.5862 Remote Similarity NPC277315
0.5862 Remote Similarity NPC472016
0.5862 Remote Similarity NPC192831
0.5833 Remote Similarity NPC217472
0.569 Remote Similarity NPC295492
0.569 Remote Similarity NPC303683
0.569 Remote Similarity NPC274891
0.5667 Remote Similarity NPC206095
0.5667 Remote Similarity NPC35702
0.5667 Remote Similarity NPC224389
0.566 Remote Similarity NPC168799
0.5636 Remote Similarity NPC232880
0.56 Remote Similarity NPC474967
0.56 Remote Similarity NPC33749
0.5556 Remote Similarity NPC488563
0.551 Remote Similarity NPC150610
0.55 Remote Similarity NPC471027
0.55 Remote Similarity NPC37250
0.55 Remote Similarity NPC142703
0.55 Remote Similarity NPC152942
0.55 Remote Similarity NPC9991
0.55 Remote Similarity NPC302857
0.55 Remote Similarity NPC600892
0.5484 Remote Similarity NPC483141
0.5472 Remote Similarity NPC203124
0.5472 Remote Similarity NPC607366
0.541 Remote Similarity NPC205751
0.5385 Remote Similarity NPC328593
0.537 Remote Similarity NPC65791
0.5357 Remote Similarity NPC155209
0.5312 Remote Similarity NPC477335
0.5294 Remote Similarity NPC275519
0.5294 Remote Similarity NPC261453
0.5294 Remote Similarity NPC217052
0.5294 Remote Similarity NPC329344
0.5294 Remote Similarity NPC237506
0.5294 Remote Similarity NPC32626
0.5246 Remote Similarity NPC477333
0.5238 Remote Similarity NPC284948
0.5238 Remote Similarity NPC303090
0.5238 Remote Similarity NPC163883
0.5238 Remote Similarity NPC301382
0.5238 Remote Similarity NPC37331
0.5192 Remote Similarity NPC147654
0.5167 Remote Similarity NPC600402
0.5091 Remote Similarity NPC106406
0.5091 Remote Similarity NPC605000
0.5085 Remote Similarity NPC476873
0.5082 Remote Similarity NPC611548
0.5077 Remote Similarity NPC477294
0.5075 Remote Similarity NPC297517
0.5075 Remote Similarity NPC306343

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474275 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
0.5238 Remote Similarity NPD6190 Approved

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