Natural Product: NPC64103

Natural Product IDNPC64103
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PSZXKZGDJMPMIO-XYFZXANASA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 PSZXKZGDJMPMIO-XYFZXANASA-N
Standard InCHI InChI=1S/C16H24O9/c1-22-9-5-8(3-4-17)6-10(23-2)15(9)25-16-14(21)13(20)12(19)11(7-18)24-16/h5-6,11-14,16-21H,3-4,7H2,1-2H3/t11-,12-,13+,14-,16-/m1/s1
SMILES COc1cc(CCO)cc(c1O[C@@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.14 Volume:   339.382
?
Van der Waals volume.
Dense:   1.061 LogP:   -0.905
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.439
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.061
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   12.0
TPSA:   138.07
?
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:   0.39 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.564 Fsp3:   0.625
MCE-18:   50.769
?
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:   0.552 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.135
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.05
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.217 Promiscuous compounds:   0.032

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.334 MDCK Permeability:   -4.856
Pgp-inhibitor:   0.0 Pgp-substrate:   0.71
PAMPA:   0.951
?
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):   0.245
20% Bioavailability (F20%):   0.052 30% Bioavailability (F30%):   0.283
50% Bioavailability (F50%):   0.88

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.187
Plasma Protein Binding (PPB):   54.628% Volume Distribution (VD):   -0.156
Fu: 47.274%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.06
BSEP inhibitor:   0.343

ADMET: Metabolism

CYP1A2-inhibitor:   0.231 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.018 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.164 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.01 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   0.025 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.015
HLM stability:   0.018
?
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):  2.851 Half-life (T1/2):  3.55

ADMET: Toxicity

hERG Blockers:  0.023 hERG Blockers (10um):  0.126
Human Hepatotoxicity (H-HT):  0.612 Drug-induced Liver Injury (DILI):  0.359
AMES Toxicity:  0.635 Rat Oral Acute Toxicity:  0.016
Maximum Recommended Daily Dose:  0.011 Skin Sensitization:  0.985
Carcinogencity:  0.212 Eye Corrosion:  0.0
Eye Irritation:  0.476 Respiratory Toxicity:  0.027
Drug-induced Neurotoxicity:  0.039 Ototoxicity:  0.951
Hematotoxicity:  0.387 Drug-induced Nephrotoxicity:  0.641
Genotoxicity:  0.013 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.07 Hek293 Cytotoxicity:  0.083
BCF:   0.278
?
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:   2.414
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.805
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.116
?
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
NPO28450 Phyllanthus emblica Species Phyllanthaceae Eukaryota n.a. n.a. n.a. PMID[11754604]
NPO28450 Phyllanthus emblica Species Phyllanthaceae Eukaryota Roots Simao city, Yunnan Province, China 2007-MAY PMID[19374435]
NPO28450 Phyllanthus emblica Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28450 Phyllanthus emblica Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28450 Phyllanthus emblica Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28450 Phyllanthus emblica Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28450 Phyllanthus emblica Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28450 Phyllanthus emblica Species Phyllanthaceae 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 NPC64103 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 NPC69513
0.7959 Intermediate Similarity NPC215833
0.75 Intermediate Similarity NPC299144
0.7059 Intermediate Similarity NPC48863
0.7059 Intermediate Similarity NPC251981
0.7059 Intermediate Similarity NPC13745
0.6875 Remote Similarity NPC217854
0.6792 Remote Similarity NPC49074
0.6667 Remote Similarity NPC162093
0.66 Remote Similarity NPC152722
0.6545 Remote Similarity NPC210478
0.6364 Remote Similarity NPC472024
0.6364 Remote Similarity NPC270849
0.6327 Remote Similarity NPC276195
0.6316 Remote Similarity NPC95392
0.6316 Remote Similarity NPC84013
0.6316 Remote Similarity NPC55715
0.6316 Remote Similarity NPC35877
0.629 Remote Similarity NPC479447
0.625 Remote Similarity NPC26653
0.625 Remote Similarity NPC80600
0.6207 Remote Similarity NPC232673
0.6111 Remote Similarity NPC95292
0.6102 Remote Similarity NPC470236
0.6 Remote Similarity NPC9912
0.5968 Remote Similarity NPC475096
0.5862 Remote Similarity NPC479029
0.5833 Remote Similarity NPC228907
0.5821 Remote Similarity NPC199539
0.5818 Remote Similarity NPC166040
0.5769 Remote Similarity NPC153149
0.5741 Remote Similarity NPC608788
0.566 Remote Similarity NPC25817
0.5652 Remote Similarity NPC605526
0.5645 Remote Similarity NPC479030
0.5625 Remote Similarity NPC216129
0.5625 Remote Similarity NPC130449
0.5625 Remote Similarity NPC248132
0.5614 Remote Similarity NPC218685
0.5556 Remote Similarity NPC60589
0.5556 Remote Similarity NPC469708
0.5522 Remote Similarity NPC61594
0.5472 Remote Similarity NPC192810
0.5469 Remote Similarity NPC210192
0.5455 Remote Similarity NPC226712
0.5441 Remote Similarity NPC56735
0.5397 Remote Similarity NPC486107
0.5385 Remote Similarity NPC212729
0.5385 Remote Similarity NPC485147
0.5385 Remote Similarity NPC604498
0.5357 Remote Similarity NPC145900
0.5333 Remote Similarity NPC248355
0.5312 Remote Similarity NPC146803
0.5312 Remote Similarity NPC164857
0.5303 Remote Similarity NPC148273
0.5294 Remote Similarity NPC51328
0.5294 Remote Similarity NPC55158
0.5283 Remote Similarity NPC269242
0.5273 Remote Similarity NPC190730
0.5273 Remote Similarity NPC609376
0.5254 Remote Similarity NPC479028
0.5254 Remote Similarity NPC23084
0.5254 Remote Similarity NPC479031
0.5254 Remote Similarity NPC19470
0.5246 Remote Similarity NPC55040
0.5246 Remote Similarity NPC104167
0.5238 Remote Similarity NPC134260
0.5231 Remote Similarity NPC475084
0.5217 Remote Similarity NPC227902
0.5185 Remote Similarity NPC294470
0.5179 Remote Similarity NPC12308
0.5172 Remote Similarity NPC40377
0.5172 Remote Similarity NPC310661
0.5167 Remote Similarity NPC210015
0.5167 Remote Similarity NPC164599
0.5161 Remote Similarity NPC302378
0.5161 Remote Similarity NPC34456
0.5147 Remote Similarity NPC158635
0.5147 Remote Similarity NPC229882
0.5094 Remote Similarity NPC142319
0.5088 Remote Similarity NPC221090
0.5077 Remote Similarity NPC604892
0.5075 Remote Similarity NPC486104
0.5075 Remote Similarity NPC486102

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC64103 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
0.5455 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