Natural Product: NPC474300

Natural Product IDNPC474300
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cinnamoyl Alkannin
IUPAC Name [(1S)-1-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] (E)-3-phenylprop-2-enoate
Synonyms Cinnamoyl Alkannin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464881
PubChem CID 44567154
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000023] Naphthalenes
        • [CHEMONTID:0000153] Naphthoquinones

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 BXLJKAWHYOWTSY-TZTLJZABSA-N
Standard InCHI InChI=1S/C25H22O6/c1-15(2)8-12-21(31-22(29)13-9-16-6-4-3-5-7-16)17-14-20(28)23-18(26)10-11-19(27)24(23)25(17)30/h3-11,13-14,21,26-27H,12H2,1-2H3/b13-9+/t21-/m0/s1
SMILES O=C(O[C@H](C1=CC(=O)c2c(C1=O)c(O)ccc2O)CC=C(C)C)/C=C/c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.14 Volume:   436.391
?
Van der Waals volume.
Dense:   0.958 LogP:   5.246
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.259
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.594
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   22.0
TPSA:   100.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.312 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.332 Fsp3:   0.16
MCE-18:   60.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   1.0 Fluc inhibitor:   0.882
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.794
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.961
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.52 Promiscuous compounds:   0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.981 MDCK Permeability:   -4.677
Pgp-inhibitor:   0.054 Pgp-substrate:   0.002
PAMPA:   0.986
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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):   0.005
20% Bioavailability (F20%):   0.037 30% Bioavailability (F30%):   0.317
50% Bioavailability (F50%):   0.673

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.832
Plasma Protein Binding (PPB):   98.269% Volume Distribution (VD):   0.414
Fu: 1.589%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.0
BSEP inhibitor:   0.626

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.957
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.591
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.183
?
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):  11.89 Half-life (T1/2):  1.13

ADMET: Toxicity

hERG Blockers:  0.091 hERG Blockers (10um):  0.498
Human Hepatotoxicity (H-HT):  0.814 Drug-induced Liver Injury (DILI):  0.966
AMES Toxicity:  0.928 Rat Oral Acute Toxicity:  0.288
Maximum Recommended Daily Dose:  0.771 Skin Sensitization:  0.997
Carcinogencity:  0.557 Eye Corrosion:  0.0
Eye Irritation:  0.733 Respiratory Toxicity:  0.644
Drug-induced Neurotoxicity:  0.588 Ototoxicity:  0.359
Hematotoxicity:  0.622 Drug-induced Nephrotoxicity:  0.915
Genotoxicity:  0.976 RPMI-8226 Immunitoxicity:  0.36
A549 Cytotoxicity:  0.82 Hek293 Cytotoxicity:  0.578
BCF:   1.546
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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:   5.183
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.622
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.454
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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
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[12502328]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[7775984]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11421 Arnebia euchroma Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11421 Arnebia euchroma Species Boraginaceae 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
NPT377 Cell line OVCAR-3 Homo sapiens CD50 = 2.4 ug ml-1 PMID[19908867]
NPT165 Cell line HeLa Homo sapiens CD50 = 3.6 ug ml-1 PubChem BioAssay data set
NPT65 Cell line HepG2 Homo sapiens CD50 = 3.8 ug ml-1 PMID[18519713]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MBC = 100.0 ug ml-1 PMID[16570920]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC = 25.0 ug.mL-1 PMID[18989978]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MBC > 100.0 ug ml-1 PMID[16570920]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC = 100.0 ug.mL-1 PMID[17521907]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MBC > 100.0 ug ml-1 Open TG-GATES in vivo data: Hematology
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 50.0 ug.mL-1 PMID[15497935]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MBC = 100.0 ug ml-1 Open TG-GATES in vivo data: Hematology
NPT1531 Organism Enterococcus faecium Enterococcus faecium MBC = 100.0 ug ml-1 PMID[15214779]
NPT1531 Organism Enterococcus faecium Enterococcus faecium MIC = 25.0 ug.mL-1 PMID[21115251]

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 NPC474300 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
0.7368 Intermediate Similarity NPC111422
0.7368 Intermediate Similarity NPC29771
0.7246 Intermediate Similarity NPC474301
0.7143 Intermediate Similarity NPC216312
0.7143 Intermediate Similarity NPC299405
0.7018 Intermediate Similarity NPC256463
0.6833 Remote Similarity NPC147542
0.6833 Remote Similarity NPC220496
0.6833 Remote Similarity NPC327916
0.678 Remote Similarity NPC241349
0.678 Remote Similarity NPC306835
0.678 Remote Similarity NPC37992
0.6667 Remote Similarity NPC32749
0.6667 Remote Similarity NPC42262
0.6557 Remote Similarity NPC257003
0.6557 Remote Similarity NPC476477
0.6508 Remote Similarity NPC476473
0.6452 Remote Similarity NPC471602
0.5857 Remote Similarity NPC471444
0.5588 Remote Similarity NPC274085
0.5373 Remote Similarity NPC89664

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474300 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