Natural Product: NPC98477

Natural Product IDNPC98477
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WTMGLHDWVJDFJD-RKQHYHRCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11723266
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 WTMGLHDWVJDFJD-RKQHYHRCSA-N
Standard InCHI InChI=1S/C14H20O8/c1-6-8(16)3-7(4-9(6)20-2)21-14-13(19)12(18)11(17)10(5-15)22-14/h3-4,10-19H,5H2,1-2H3/t10-,11-,12+,13-,14-/m1/s1
SMILES Cc1c(cc(cc1OC)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:   316.12 Volume:   296.0
?
Van der Waals volume.
Dense:   1.068 LogP:   0.043
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.547
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.336
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   128.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.473 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.609 Fsp3:   0.571
MCE-18:   51.818
?
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:   0.537 Fluc inhibitor:   0.013
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.247
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.076
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.192 Promiscuous compounds:   0.206

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.047 MDCK Permeability:   -5.132
Pgp-inhibitor:   0.001 Pgp-substrate:   0.229
PAMPA:   0.923
?
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):   0.808
20% Bioavailability (F20%):   0.212 30% Bioavailability (F30%):   0.915
50% Bioavailability (F50%):   0.871

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.036 MRP1:   0.181
Plasma Protein Binding (PPB):   77.057% Volume Distribution (VD):   -0.071
Fu: 22.544%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.202
BSEP inhibitor:   0.003

ADMET: Metabolism

CYP1A2-inhibitor:   0.265 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.033 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.234
HLM stability:   0.021
?
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):  2.51 Half-life (T1/2):  3.687

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.15
Human Hepatotoxicity (H-HT):  0.668 Drug-induced Liver Injury (DILI):  0.774
AMES Toxicity:  0.889 Rat Oral Acute Toxicity:  0.029
Maximum Recommended Daily Dose:  0.018 Skin Sensitization:  0.994
Carcinogencity:  0.318 Eye Corrosion:  0.001
Eye Irritation:  0.628 Respiratory Toxicity:  0.058
Drug-induced Neurotoxicity:  0.024 Ototoxicity:  0.887
Hematotoxicity:  0.35 Drug-induced Nephrotoxicity:  0.667
Genotoxicity:  0.194 RPMI-8226 Immunitoxicity:  0.107
A549 Cytotoxicity:  0.196 Hek293 Cytotoxicity:  0.181
BCF:   0.267
?
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:   2.271
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.798
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.988
?
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
NPO16098 Boronia pinnata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[11076549]
NPO22142 Hippocratea excelsa Species n.a. n.a. n.a. root n.a. PMID[17385912]
NPO22142 Hippocratea excelsa Species n.a. n.a. root bark n.a. n.a. PMID[17385912]
NPO6364 Pongamiopsis pervilleana Species Fabaceae Eukaryota n.a. Madagascar Dry Forest n.a. PMID[20804165]
NPO22142 Hippocratea excelsa Species n.a. n.a. n.a. n.a. n.a. PMID[2292687]
NPO7890 Cleistanthus indochinensis Species Phyllanthaceae Eukaryota fruits n.a. n.a. PMID[22938151]
NPO7890 Cleistanthus indochinensis Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12835 Cyrtomium falcatum Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12101 Ajuga genevensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15005 Sargassum muticum Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16098 Boronia pinnata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8679 Streptomyces sparsogenes Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO15319 Glochidion sphaerogynum Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21904 Tarenaya spinosa Species Cleomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17282 Pinguicula vulgaris Species Lentibulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12835 Cyrtomium falcatum Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15319 Glochidion sphaerogynum Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22142 Hippocratea excelsa Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO6364 Pongamiopsis pervilleana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15005 Sargassum muticum Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1118 Elymus repens Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7890 Cleistanthus indochinensis Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16098 Boronia pinnata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8679 Streptomyces sparsogenes Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO12101 Ajuga genevensis Species Lamiaceae 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 NPC98477 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
0.7692 Intermediate Similarity NPC23084
0.6667 Remote Similarity NPC604892
0.6604 Remote Similarity NPC145900
0.6471 Remote Similarity NPC192810
0.64 Remote Similarity NPC276195
0.6349 Remote Similarity NPC606849
0.6346 Remote Similarity NPC152722
0.6275 Remote Similarity NPC217854
0.619 Remote Similarity NPC99233
0.6182 Remote Similarity NPC214454
0.6111 Remote Similarity NPC12308
0.6061 Remote Similarity NPC219163
0.6032 Remote Similarity NPC210192
0.6 Remote Similarity NPC221090
0.5965 Remote Similarity NPC218685
0.5849 Remote Similarity NPC153149
0.5846 Remote Similarity NPC30432
0.5821 Remote Similarity NPC486379
0.5769 Remote Similarity NPC142319
0.5758 Remote Similarity NPC604833
0.5741 Remote Similarity NPC25817
0.5735 Remote Similarity NPC106625
0.5672 Remote Similarity NPC308265
0.5672 Remote Similarity NPC97052
0.5672 Remote Similarity NPC76128
0.5672 Remote Similarity NPC163191
0.5636 Remote Similarity NPC299144
0.5634 Remote Similarity NPC236934
0.5588 Remote Similarity NPC39351
0.5574 Remote Similarity NPC222455
0.5574 Remote Similarity NPC599943
0.5571 Remote Similarity NPC300537
0.5556 Remote Similarity NPC134260
0.5507 Remote Similarity NPC149244
0.5472 Remote Similarity NPC212729
0.5472 Remote Similarity NPC604498
0.5469 Remote Similarity NPC111536
0.5439 Remote Similarity NPC69513
0.5429 Remote Similarity NPC29830
0.541 Remote Similarity NPC473044
0.537 Remote Similarity NPC269242
0.537 Remote Similarity NPC484157
0.5357 Remote Similarity NPC60589
0.5357 Remote Similarity NPC469708
0.5357 Remote Similarity NPC609376
0.5345 Remote Similarity NPC48863
0.5345 Remote Similarity NPC251981
0.5345 Remote Similarity NPC13745
0.5333 Remote Similarity NPC479028
0.5333 Remote Similarity NPC479031
0.5323 Remote Similarity NPC106025
0.5312 Remote Similarity NPC294166
0.5312 Remote Similarity NPC115022
0.5294 Remote Similarity NPC228907
0.5273 Remote Similarity NPC294470
0.5254 Remote Similarity NPC40377
0.5254 Remote Similarity NPC310661
0.5254 Remote Similarity NPC215833
0.5246 Remote Similarity NPC214910
0.5246 Remote Similarity NPC26080
0.5246 Remote Similarity NPC165686
0.5238 Remote Similarity NPC473045
0.5231 Remote Similarity NPC479030
0.5231 Remote Similarity NPC8497
0.5231 Remote Similarity NPC479374
0.5179 Remote Similarity NPC9248
0.5167 Remote Similarity NPC49074
0.5161 Remote Similarity NPC609351
0.5156 Remote Similarity NPC199335
0.5156 Remote Similarity NPC477240
0.5152 Remote Similarity NPC121001
0.5152 Remote Similarity NPC600107
0.5147 Remote Similarity NPC605700
0.5143 Remote Similarity NPC488085
0.5085 Remote Similarity NPC166168
0.5085 Remote Similarity NPC166040
0.5085 Remote Similarity NPC95292
0.5085 Remote Similarity NPC604209
0.5082 Remote Similarity NPC162093
0.5082 Remote Similarity NPC270849
0.5082 Remote Similarity NPC19470
0.5082 Remote Similarity NPC606892
0.5079 Remote Similarity NPC189589
0.5079 Remote Similarity NPC104167
0.5077 Remote Similarity NPC190217
0.5075 Remote Similarity NPC98777
0.5075 Remote Similarity NPC189115
0.5075 Remote Similarity NPC212770
0.507 Remote Similarity NPC206378

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC98477 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