Natural Product: NPC65791

Natural Product IDNPC65791
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Umbelactonyl Caffeate
IUPAC Name [(2R)-3-methyl-5-oxo-2H-furan-2-yl]methyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms Umbelactonyl Caffeate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL502070
PubChem CID 11737833
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 HBXZQGVBVFMZGQ-LQPUYASZSA-N
Standard InCHI InChI=1S/C15H14O6/c1-9-6-15(19)21-13(9)8-20-14(18)5-3-10-2-4-11(16)12(17)7-10/h2-7,13,16-17H,8H2,1H3/b5-3+/t13-/m0/s1
SMILES CC1=CC(=O)O[C@H]1COC(=O)/C=C/c1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.08 Volume:   285.169
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Van der Waals volume.
Dense:   1.017 LogP:   2.189
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.373
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.66
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   93.06
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.496 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.262 Fsp3:   0.2
MCE-18:   40.444
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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:   0.949 Fluc inhibitor:   1.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.15
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.199
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.617 Promiscuous compounds:   0.513

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.468 MDCK Permeability:   -4.783
Pgp-inhibitor:   0.323 Pgp-substrate:   0.036
PAMPA:   0.451
?
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):   0.1
20% Bioavailability (F20%):   0.975 30% Bioavailability (F30%):   0.983
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.278
Plasma Protein Binding (PPB):   86.051% Volume Distribution (VD):   -0.477
Fu: 11.063%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.063
BSEP inhibitor:   0.81

ADMET: Metabolism

CYP1A2-inhibitor:   0.08 CYP1A2-substrate:   0.433
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.033
CYP2C9-inhibitor:   0.054 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.941
CYP3A4-inhibitor:   0.011 CYP3A4-substrate:   0.92
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.84
?
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):  12.918 Half-life (T1/2):  1.343

ADMET: Toxicity

hERG Blockers:  0.062 hERG Blockers (10um):  0.595
Human Hepatotoxicity (H-HT):  0.399 Drug-induced Liver Injury (DILI):  0.755
AMES Toxicity:  0.711 Rat Oral Acute Toxicity:  0.23
Maximum Recommended Daily Dose:  0.577 Skin Sensitization:  0.999
Carcinogencity:  0.482 Eye Corrosion:  0.431
Eye Irritation:  0.974 Respiratory Toxicity:  0.086
Drug-induced Neurotoxicity:  0.22 Ototoxicity:  0.374
Hematotoxicity:  0.082 Drug-induced Nephrotoxicity:  0.295
Genotoxicity:  0.793 RPMI-8226 Immunitoxicity:  0.03
A549 Cytotoxicity:  0.428 Hek293 Cytotoxicity:  0.206
BCF:   0.862
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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:   3.652
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.921
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.598
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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
NPO18159 Crypteronia paniculata Species Crypteroniaceae Eukaryota n.a. n.a. n.a. PMID[12502343]
NPO18159 Crypteronia paniculata Species Crypteroniaceae Eukaryota n.a. n.a. n.a. PMID[15787463]
NPO18159 Crypteronia paniculata Species Crypteroniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18159 Crypteronia paniculata Species Crypteroniaceae 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
NPT2 Others Unspecified n.a. Activity = 92.0 % PubChem BioAssay data set
NPT2 Others Unspecified n.a. Activity = 88.0 % PMID[9644059]
NPT2 Others Unspecified n.a. Activity = 68.0 % PMID[9644059]
NPT2 Others Unspecified n.a. Activity = 32.0 % PMID[9644059]
NPT2 Others Unspecified n.a. Activity = 16.0 % PMID[9644059]

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 NPC65791 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
0.6889 Remote Similarity NPC95381
0.6531 Remote Similarity NPC261453
0.62 Remote Similarity NPC474967
0.62 Remote Similarity NPC33749
0.6122 Remote Similarity NPC217472
0.5962 Remote Similarity NPC328593
0.5882 Remote Similarity NPC233669
0.587 Remote Similarity NPC226250
0.5818 Remote Similarity NPC474895
0.5769 Remote Similarity NPC147654
0.5769 Remote Similarity NPC281277
0.5741 Remote Similarity NPC203124
0.5741 Remote Similarity NPC607366
0.566 Remote Similarity NPC147192
0.566 Remote Similarity NPC309434
0.5625 Remote Similarity NPC304638
0.5614 Remote Similarity NPC155209
0.5593 Remote Similarity NPC476873
0.5556 Remote Similarity NPC263386
0.5556 Remote Similarity NPC141791
0.5424 Remote Similarity NPC482045
0.537 Remote Similarity NPC474275
0.537 Remote Similarity NPC224208
0.537 Remote Similarity NPC41661
0.5303 Remote Similarity NPC481154
0.5263 Remote Similarity NPC470849
0.5246 Remote Similarity NPC474875
0.5231 Remote Similarity NPC470572
0.5192 Remote Similarity NPC150610
0.5147 Remote Similarity NPC270993
0.5147 Remote Similarity NPC481155
0.5088 Remote Similarity NPC168799
0.5085 Remote Similarity NPC470848
0.5075 Remote Similarity NPC477294
0.5072 Remote Similarity NPC156875

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC65791 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