Natural Product: NPC59539

Natural Product IDNPC59539
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PYMYPHUHKUWMLA-YUPRTTJUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 644176
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0001540] Monosaccharides
            • [CHEMONTID:0001497] Pentoses

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 PYMYPHUHKUWMLA-YUPRTTJUSA-N
Standard InCHI InChI=1S/C5H10O5/c6-1-3(8)5(10)4(9)2-7/h1,3-5,7-10H,2H2/t3-,4-,5-/m0/s1
SMILES C(=O)[C@@H]([C@@H]([C@H](CO)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   150.05 Volume:   136.351
?
Van der Waals volume.
Dense:   1.1 LogP:   -1.793
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -1.102
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.181
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   1.0
TPSA:   97.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   0.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.326 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.765 Fsp3:   0.8
MCE-18:   3.0
?
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:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.045 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.034
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.776 Promiscuous compounds:   0.162

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.918 MDCK Permeability:   -4.415
Pgp-inhibitor:   0.0 Pgp-substrate:   0.551
PAMPA:   0.995
?
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):   0.715
20% Bioavailability (F20%):   0.552 30% Bioavailability (F30%):   0.875
50% Bioavailability (F50%):   0.813

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.296 MRP1:   0.027
Plasma Protein Binding (PPB):   26.253% Volume Distribution (VD):   -0.542
Fu: 83.041%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.937
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.054
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.011
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.058
CYP2C9-inhibitor:   0.345 CYP2C9-substrate:   0.021
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.896
HLM stability:   0.149
?
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):  3.675 Half-life (T1/2):  2.009

ADMET: Toxicity

hERG Blockers:  0.005 hERG Blockers (10um):  0.025
Human Hepatotoxicity (H-HT):  0.446 Drug-induced Liver Injury (DILI):  0.012
AMES Toxicity:  0.835 Rat Oral Acute Toxicity:  0.011
Maximum Recommended Daily Dose:  0.023 Skin Sensitization:  0.968
Carcinogencity:  0.376 Eye Corrosion:  0.003
Eye Irritation:  0.731 Respiratory Toxicity:  0.003
Drug-induced Neurotoxicity:  0.021 Ototoxicity:  0.927
Hematotoxicity:  0.148 Drug-induced Nephrotoxicity:  0.427
Genotoxicity:  0.2 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.011 Hek293 Cytotoxicity:  0.031
BCF:   0.146
?
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:   2.203
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.77
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.073
?
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
NPO48692 Quercus ilex subsp. ballota (Desf.) Samp. Genus Fagaceae Eukaryota n.a. n.a. n.a. PMID[36233184]
NPO25890 Herba cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23795 Herba seu radix cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO19689 Radix cirsii japonici Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25890 Herba cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO19689 Radix cirsii japonici Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23795 Herba seu radix cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]

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
NPO48692 Quercus ilex subsp. ballota (Desf.) Samp. n.a. n.a. 2.8651 n.a. n.a. % PMID[36233184]

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 NPC59539 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 NPC270088
1.0 High Similarity NPC200137
0.8333 Intermediate Similarity NPC606151
0.5882 Remote Similarity NPC261351
0.5294 Remote Similarity NPC293908
0.5294 Remote Similarity NPC66052
0.5294 Remote Similarity NPC192065
0.5294 Remote Similarity NPC197207
0.5294 Remote Similarity NPC187058
0.5294 Remote Similarity NPC86412
0.5294 Remote Similarity NPC182541
0.5294 Remote Similarity NPC127074
0.5294 Remote Similarity NPC149070
0.5217 Remote Similarity NPC605100

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59539 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
0.8333 Intermediate Similarity NPD9001 Phase 2
0.8333 Intermediate Similarity NPD9002 Approved
0.5294 Remote Similarity NPD8814 Phase 3
0.5294 Remote Similarity NPD9051 Approved
0.5294 Remote Similarity NPD9052 Phase 4
0.5294 Remote Similarity NPD9053 Phase 4

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