Natural Product: NPC303683

Natural Product IDNPC303683
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (1R,3R,4S,5R)-Methyl 3-(3-(3,4-Dihydroxyphenyl)Acryloyloxy)-1,4,5-Trihydroxycyclohexanecarboxylate
IUPAC Name methyl (1R,3R,4S,5R)-3-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy-1,4,5-trihydroxycyclohexane-1-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL596924
PubChem CID 46230348
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000129] Alcohols and polyols
          • [CHEMONTID:0001292] Cyclic alcohols and derivatives
            • [CHEMONTID:0002509] Cyclitols and derivatives
              • [CHEMONTID:0002512] Quinic 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 MZNIJRAPCCELQX-NYCIAPANSA-N
Standard InCHI InChI=1S/C17H20O9/c1-25-16(23)17(24)7-12(20)15(22)13(8-17)26-14(21)5-3-9-2-4-10(18)11(19)6-9/h2-6,12-13,15,18-20,22,24H,7-8H2,1H3/b5-3+/t12-,13-,15+,17-/m1/s1
SMILES COC(=O)[C@@]1(O)C[C@@H](O)[C@@H]([C@@H](C1)OC(=O)/C=C/c1ccc(c(c1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.11 Volume:   348.769
?
Van der Waals volume.
Dense:   1.055 LogP:   1.259
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.454
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.078
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   153.75
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.267 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.893 Fsp3:   0.412
MCE-18:   59.5
?
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:   0.582 Fluc inhibitor:   0.76
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.065
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.278
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.278 Promiscuous compounds:   0.433

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.085 MDCK Permeability:   -5.132
Pgp-inhibitor:   0.0 Pgp-substrate:   0.481
PAMPA:   0.978
?
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):   0.52
20% Bioavailability (F20%):   0.998 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.484
Plasma Protein Binding (PPB):   60.952% Volume Distribution (VD):   0.332
Fu: 39.886%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.039
BSEP inhibitor:   0.027

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.972
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.442
?
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):  5.823 Half-life (T1/2):  2.452

ADMET: Toxicity

hERG Blockers:  0.037 hERG Blockers (10um):  0.202
Human Hepatotoxicity (H-HT):  0.563 Drug-induced Liver Injury (DILI):  0.154
AMES Toxicity:  0.352 Rat Oral Acute Toxicity:  0.027
Maximum Recommended Daily Dose:  0.939 Skin Sensitization:  0.975
Carcinogencity:  0.255 Eye Corrosion:  0.003
Eye Irritation:  0.515 Respiratory Toxicity:  0.048
Drug-induced Neurotoxicity:  0.013 Ototoxicity:  0.827
Hematotoxicity:  0.029 Drug-induced Nephrotoxicity:  0.625
Genotoxicity:  0.665 RPMI-8226 Immunitoxicity:  0.033
A549 Cytotoxicity:  0.17 Hek293 Cytotoxicity:  0.102
BCF:   0.577
?
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:   3.272
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.95
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.302
?
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
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. whole plant n.a. PMID[21428416]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[22870812]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23435948]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[25737008]
NPO40024 Arcytophyllum thymifolium Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27509358]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. pericarp n.a. PMID[p25172756]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11170 Akebia trifoliata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11100 Artemisia capillaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19649 Akebia quinata Species Lardizabalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11170 Akebia trifoliata Species Lardizabalaceae 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
NPT25 Cell line MT4 Homo sapiens CC100 > 25.0 ug ml-1 PMID[20004585]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1.4 ug.mL-1 PMID[20004585]
NPT1 Others Radical scavenging activity n.a. EC50 = 20.0 ug.mL-1 PMID[20004585]

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 NPC303683 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
1.0 High Similarity NPC295492
1.0 High Similarity NPC274891
0.8421 Intermediate Similarity NPC205751
0.8364 Intermediate Similarity NPC233350
0.8364 Intermediate Similarity NPC70680
0.7963 Intermediate Similarity NPC258469
0.7963 Intermediate Similarity NPC43158
0.7963 Intermediate Similarity NPC610147
0.6897 Remote Similarity NPC26241
0.6885 Remote Similarity NPC277315
0.6885 Remote Similarity NPC472016
0.6885 Remote Similarity NPC192831
0.6852 Remote Similarity NPC224208
0.6852 Remote Similarity NPC41661
0.6719 Remote Similarity NPC163883
0.6 Remote Similarity NPC306343
0.5915 Remote Similarity NPC93498
0.5857 Remote Similarity NPC146277
0.5781 Remote Similarity NPC474875
0.5758 Remote Similarity NPC37250
0.5758 Remote Similarity NPC142703
0.5758 Remote Similarity NPC152942
0.5758 Remote Similarity NPC9991
0.5758 Remote Similarity NPC302857
0.5758 Remote Similarity NPC600892
0.569 Remote Similarity NPC474275
0.5645 Remote Similarity NPC182217
0.5577 Remote Similarity NPC226250
0.5568 Remote Similarity NPC471823
0.5507 Remote Similarity NPC284948
0.5507 Remote Similarity NPC303090
0.5507 Remote Similarity NPC301382
0.5507 Remote Similarity NPC37331
0.5424 Remote Similarity NPC147192
0.5417 Remote Similarity NPC322660
0.541 Remote Similarity NPC168799
0.5385 Remote Similarity NPC13818
0.5345 Remote Similarity NPC233669
0.5254 Remote Similarity NPC281277
0.5205 Remote Similarity NPC220664
0.5205 Remote Similarity NPC270993
0.5195 Remote Similarity NPC19380
0.5167 Remote Similarity NPC309434
0.5161 Remote Similarity NPC227297
0.5128 Remote Similarity NPC471076
0.5079 Remote Similarity NPC470849
0.5079 Remote Similarity NPC488563
0.5079 Remote Similarity NPC474895
0.5072 Remote Similarity NPC471027

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC303683 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
0.5507 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