Natural Product: NPC174832

Natural Product IDNPC174832
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ARYSAKCPIBLSDO-RGCYKPLRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 23928130
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 ARYSAKCPIBLSDO-RGCYKPLRSA-N
Standard InCHI InChI=1S/C14H18O9/c1-5(16)10-7(17)2-6(3-8(10)18)22-14-13(21)12(20)11(19)9(4-15)23-14/h2-3,9,11-15,17-21H,4H2,1H3/t9-,11-,12+,13-,14-/m1/s1
SMILES CC(=O)c1c(cc(cc1O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.1 Volume:   302.154
?
Van der Waals volume.
Dense:   1.092 LogP:   0.182
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.745
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.707
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   156.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.361 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.779 Fsp3:   0.5
MCE-18:   55.619
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.479 Fluc inhibitor:   0.037
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.102
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.081
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.281 Promiscuous compounds:   0.474

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.187 MDCK Permeability:   -5.101
Pgp-inhibitor:   0.0 Pgp-substrate:   0.256
PAMPA:   0.976
?
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):   0.435
20% Bioavailability (F20%):   0.08 30% Bioavailability (F30%):   0.94
50% Bioavailability (F50%):   0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.046 MRP1:   0.097
Plasma Protein Binding (PPB):   74.03% Volume Distribution (VD):   -0.328
Fu: 27.224%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.07
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.649 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.012 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.02 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.133
HLM stability:   0.495
?
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):  3.08 Half-life (T1/2):  2.927

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.132
Human Hepatotoxicity (H-HT):  0.59 Drug-induced Liver Injury (DILI):  0.888
AMES Toxicity:  0.876 Rat Oral Acute Toxicity:  0.019
Maximum Recommended Daily Dose:  0.018 Skin Sensitization:  0.996
Carcinogencity:  0.124 Eye Corrosion:  0.0
Eye Irritation:  0.782 Respiratory Toxicity:  0.123
Drug-induced Neurotoxicity:  0.005 Ototoxicity:  0.891
Hematotoxicity:  0.347 Drug-induced Nephrotoxicity:  0.662
Genotoxicity:  0.569 RPMI-8226 Immunitoxicity:  0.124
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.235
BCF:   0.179
?
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:   2.574
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.026
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.221
?
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
NPO28099 Epimedium cremeum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27987 Clavelina cylindrica Species Clavelinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28419 Tribolium confusum Species Tenebrionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28099 Epimedium cremeum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27987 Clavelina cylindrica Species Clavelinidae 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 NPC174832 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
0.8478 Intermediate Similarity NPC214454
0.76 Intermediate Similarity NPC23084
0.7021 Intermediate Similarity NPC294470
0.6667 Remote Similarity NPC479374
0.6596 Remote Similarity NPC142319
0.6552 Remote Similarity NPC121001
0.6545 Remote Similarity NPC222455
0.6296 Remote Similarity NPC205054
0.6275 Remote Similarity NPC12308
0.625 Remote Similarity NPC106025
0.625 Remote Similarity NPC212729
0.625 Remote Similarity NPC604498
0.6122 Remote Similarity NPC269242
0.6111 Remote Similarity NPC218685
0.6102 Remote Similarity NPC111536
0.6087 Remote Similarity NPC228907
0.6078 Remote Similarity NPC60589
0.6078 Remote Similarity NPC469708
0.6034 Remote Similarity NPC199335
0.6034 Remote Similarity NPC477240
0.6 Remote Similarity NPC192810
0.5962 Remote Similarity NPC200092
0.5932 Remote Similarity NPC190217
0.5882 Remote Similarity NPC9248
0.5882 Remote Similarity NPC152722
0.5849 Remote Similarity NPC221090
0.5849 Remote Similarity NPC145900
0.5833 Remote Similarity NPC8497
0.5806 Remote Similarity NPC99233
0.5806 Remote Similarity NPC57587
0.58 Remote Similarity NPC484157
0.5781 Remote Similarity NPC308265
0.5769 Remote Similarity NPC609376
0.5738 Remote Similarity NPC604892
0.5714 Remote Similarity NPC30432
0.5714 Remote Similarity NPC19470
0.5714 Remote Similarity NPC606353
0.569 Remote Similarity NPC599943
0.5686 Remote Similarity NPC153149
0.5667 Remote Similarity NPC611586
0.5636 Remote Similarity NPC40377
0.5636 Remote Similarity NPC310661
0.5614 Remote Similarity NPC26080
0.5614 Remote Similarity NPC165686
0.5614 Remote Similarity NPC481303
0.56 Remote Similarity NPC276195
0.5593 Remote Similarity NPC97326
0.5577 Remote Similarity NPC25817
0.5556 Remote Similarity NPC177742
0.5556 Remote Similarity NPC80098
0.5538 Remote Similarity NPC97052
0.5538 Remote Similarity NPC163191
0.55 Remote Similarity NPC475628
0.549 Remote Similarity NPC217854
0.5484 Remote Similarity NPC216752
0.5472 Remote Similarity NPC604439
0.5469 Remote Similarity NPC606849
0.5455 Remote Similarity NPC166168
0.5455 Remote Similarity NPC219163
0.5455 Remote Similarity NPC39351
0.5455 Remote Similarity NPC26195
0.5455 Remote Similarity NPC488085
0.5455 Remote Similarity NPC604209
0.5439 Remote Similarity NPC83975
0.541 Remote Similarity NPC294166
0.541 Remote Similarity NPC174377
0.541 Remote Similarity NPC115022
0.5373 Remote Similarity NPC149244
0.5373 Remote Similarity NPC106625
0.537 Remote Similarity NPC226712
0.537 Remote Similarity NPC608788
0.5357 Remote Similarity NPC9912
0.5345 Remote Similarity NPC26653
0.5345 Remote Similarity NPC214910
0.5345 Remote Similarity NPC210015
0.5333 Remote Similarity NPC85799
0.5333 Remote Similarity NPC303422
0.5333 Remote Similarity NPC218003
0.5323 Remote Similarity NPC185778
0.5323 Remote Similarity NPC610808
0.5312 Remote Similarity NPC259767
0.5294 Remote Similarity NPC29830
0.5254 Remote Similarity NPC105827
0.5238 Remote Similarity NPC600107
0.5231 Remote Similarity NPC271385
0.5231 Remote Similarity NPC605700
0.5224 Remote Similarity NPC61594
0.5224 Remote Similarity NPC486379
0.5217 Remote Similarity NPC300537
0.5185 Remote Similarity NPC299144
0.5179 Remote Similarity NPC166040
0.5172 Remote Similarity NPC251102
0.5172 Remote Similarity NPC479028
0.5172 Remote Similarity NPC270849
0.5172 Remote Similarity NPC210298
0.5172 Remote Similarity NPC479031
0.5172 Remote Similarity NPC604356
0.5172 Remote Similarity NPC606892
0.5167 Remote Similarity NPC25292
0.5161 Remote Similarity NPC242028
0.5161 Remote Similarity NPC203230
0.5156 Remote Similarity NPC98777
0.5156 Remote Similarity NPC210192
0.5156 Remote Similarity NPC189115
0.5147 Remote Similarity NPC56735
0.5147 Remote Similarity NPC147596
0.5085 Remote Similarity NPC80600
0.5082 Remote Similarity NPC59324
0.5082 Remote Similarity NPC473045
0.5082 Remote Similarity NPC483778
0.5082 Remote Similarity NPC607971
0.5082 Remote Similarity NPC609355
0.5079 Remote Similarity NPC186418
0.5077 Remote Similarity NPC178851
0.5075 Remote Similarity NPC259182
0.5075 Remote Similarity NPC88484
0.5075 Remote Similarity NPC170475
0.5075 Remote Similarity NPC76128
0.507 Remote Similarity NPC236934

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC174832 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
0.537 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