Natural Product: NPC284121

Natural Product IDNPC284121
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OYTCTPHTVUEGCL-RBKUQZRRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 25244544
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic glycosides

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 OYTCTPHTVUEGCL-RBKUQZRRSA-N
Standard InCHI InChI=1S/C17H22O9/c1-23-10-6-9(4-3-5-18)7-11(24-2)16(10)26-17-15(22)14(21)13(20)12(8-19)25-17/h3-7,12-15,17,19-22H,8H2,1-2H3/b4-3+/t12-,13-,14+,15-,17?/m1/s1
SMILES COc1cc(/C=C/C=O)cc(c1OC1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.13 Volume:   351.405
?
Van der Waals volume.
Dense:   1.053 LogP:   -0.401
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.168
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.781
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   134.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.355 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.776 Fsp3:   0.471
MCE-18:   51.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.431 Fluc inhibitor:   0.28
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.151
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.179
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.251 Promiscuous compounds:   0.017

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.446 MDCK Permeability:   -5.077
Pgp-inhibitor:   0.001 Pgp-substrate:   0.145
PAMPA:   0.945
?
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):   0.157
20% Bioavailability (F20%):   0.183 30% Bioavailability (F30%):   0.79
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.136 MRP1:   0.218
Plasma Protein Binding (PPB):   68.632% Volume Distribution (VD):   -0.541
Fu: 30.205%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.226
BSEP inhibitor:   0.092

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.068
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.948
HLM stability:   0.028
?
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):  2.726 Half-life (T1/2):  2.923

ADMET: Toxicity

hERG Blockers:  0.034 hERG Blockers (10um):  0.132
Human Hepatotoxicity (H-HT):  0.602 Drug-induced Liver Injury (DILI):  0.726
AMES Toxicity:  0.887 Rat Oral Acute Toxicity:  0.074
Maximum Recommended Daily Dose:  0.062 Skin Sensitization:  0.96
Carcinogencity:  0.463 Eye Corrosion:  0.0
Eye Irritation:  0.218 Respiratory Toxicity:  0.043
Drug-induced Neurotoxicity:  0.199 Ototoxicity:  0.874
Hematotoxicity:  0.367 Drug-induced Nephrotoxicity:  0.806
Genotoxicity:  0.685 RPMI-8226 Immunitoxicity:  0.162
A549 Cytotoxicity:  0.181 Hek293 Cytotoxicity:  0.155
BCF:   0.634
?
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:   3.236
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.044
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.211
?
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
NPO14548 Ilex rotunda Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14548 Ilex rotunda Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14548 Ilex rotunda Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14548 Ilex rotunda Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14548 Ilex rotunda Species Aquifoliaceae 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

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 NPC284121 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 NPC210478
0.8077 Intermediate Similarity NPC49074
0.7925 Intermediate Similarity NPC162093
0.7818 Intermediate Similarity NPC55040
0.7241 Intermediate Similarity NPC470236
0.7069 Intermediate Similarity NPC232673
0.6792 Remote Similarity NPC299144
0.6545 Remote Similarity NPC69513
0.65 Remote Similarity NPC302378
0.6441 Remote Similarity NPC248355
0.6441 Remote Similarity NPC479029
0.6429 Remote Similarity NPC48863
0.6429 Remote Similarity NPC251981
0.6429 Remote Similarity NPC13745
0.6349 Remote Similarity NPC164857
0.6316 Remote Similarity NPC215833
0.6226 Remote Similarity NPC217854
0.619 Remote Similarity NPC479030
0.6 Remote Similarity NPC152722
0.5938 Remote Similarity NPC37468
0.5806 Remote Similarity NPC95392
0.5806 Remote Similarity NPC84013
0.5806 Remote Similarity NPC55715
0.5806 Remote Similarity NPC35877
0.5789 Remote Similarity NPC200092
0.5758 Remote Similarity NPC475084
0.5741 Remote Similarity NPC276195
0.5606 Remote Similarity NPC474044
0.5593 Remote Similarity NPC166040
0.5593 Remote Similarity NPC95292
0.5577 Remote Similarity NPC228907
0.5574 Remote Similarity NPC479028
0.5574 Remote Similarity NPC270849
0.5574 Remote Similarity NPC479031
0.5574 Remote Similarity NPC604356
0.5556 Remote Similarity NPC104167
0.5536 Remote Similarity NPC153149
0.5517 Remote Similarity NPC608788
0.5455 Remote Similarity NPC604095
0.5439 Remote Similarity NPC25817
0.541 Remote Similarity NPC218685
0.5385 Remote Similarity NPC146540
0.5325 Remote Similarity NPC479448
0.5323 Remote Similarity NPC472024
0.5323 Remote Similarity NPC251102
0.5323 Remote Similarity NPC210298
0.5254 Remote Similarity NPC226712
0.5246 Remote Similarity NPC310661
0.5246 Remote Similarity NPC9912
0.5238 Remote Similarity NPC26653
0.5238 Remote Similarity NPC80600
0.5238 Remote Similarity NPC164599
0.5238 Remote Similarity NPC481303
0.5224 Remote Similarity NPC185778
0.5217 Remote Similarity NPC216129
0.5217 Remote Similarity NPC130449
0.5217 Remote Similarity NPC248132
0.52 Remote Similarity NPC93924
0.5179 Remote Similarity NPC212729
0.5179 Remote Similarity NPC604498
0.5152 Remote Similarity NPC100389
0.5147 Remote Similarity NPC146803
0.5143 Remote Similarity NPC479447
0.5139 Remote Similarity NPC51328
0.5139 Remote Similarity NPC55158
0.5088 Remote Similarity NPC269242
0.5085 Remote Similarity NPC60589
0.5085 Remote Similarity NPC469708
0.5085 Remote Similarity NPC609376
0.5079 Remote Similarity NPC23084
0.5075 Remote Similarity NPC294166
0.5075 Remote Similarity NPC115022
0.5072 Remote Similarity NPC475096

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC284121 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
0.5254 Remote Similarity NPD1091 Pre-clinical

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