Natural Product: NPC59817

Natural Product IDNPC59817
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZUMPYZVELBOZDM-XVVDYKMHSA-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:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-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 ZUMPYZVELBOZDM-XVVDYKMHSA-N
Standard InCHI InChI=1S/C20H18O10/c21-9-4-11(23)17-12(24)6-14(29-16(17)5-9)8-1-2-10(22)15(3-8)30-20-19(27)18(26)13(25)7-28-20/h1-6,13,18-23,25-27H,7H2/t13-,18+,19-,20-/m0/s1
SMILES c1cc(c(cc1c1cc(=O)c2c(cc(cc2o1)O)O)O[C@H]1[C@H]([C@@H]([C@H](CO1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.09 Volume:   387.061
?
Van der Waals volume.
Dense:   1.08 LogP:   1.143
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.343
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.706
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   170.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.35 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.857 Fsp3:   0.25
MCE-18:   85.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.638 Fluc inhibitor:   0.371
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.974
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.856
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.103 Promiscuous compounds:   0.812

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.152 MDCK Permeability:   -5.174
Pgp-inhibitor:   0.0 Pgp-substrate:   0.934
PAMPA:   0.959
?
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):   0.261
20% Bioavailability (F20%):   0.946 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.49
Plasma Protein Binding (PPB):   85.386% Volume Distribution (VD):   -0.033
Fu: 12.761%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.878
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.954
BSEP inhibitor:   0.011

ADMET: Metabolism

CYP1A2-inhibitor:   0.007 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.136
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.742
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.132
?
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):  2.516 Half-life (T1/2):  2.212

ADMET: Toxicity

hERG Blockers:  0.023 hERG Blockers (10um):  0.204
Human Hepatotoxicity (H-HT):  0.61 Drug-induced Liver Injury (DILI):  0.942
AMES Toxicity:  0.957 Rat Oral Acute Toxicity:  0.186
Maximum Recommended Daily Dose:  0.455 Skin Sensitization:  0.991
Carcinogencity:  0.447 Eye Corrosion:  0.001
Eye Irritation:  0.943 Respiratory Toxicity:  0.275
Drug-induced Neurotoxicity:  0.005 Ototoxicity:  0.477
Hematotoxicity:  0.121 Drug-induced Nephrotoxicity:  0.258
Genotoxicity:  0.952 RPMI-8226 Immunitoxicity:  0.157
A549 Cytotoxicity:  0.763 Hek293 Cytotoxicity:  0.727
BCF:   0.635
?
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:   3.177
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.404
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.703
?
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
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[10978218]
NPO17823 Lycium chinense Species Solanaceae Eukaryota fruits n.a. n.a. PMID[12467621]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. root n.a. PMID[16212233]
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota stem n.a. n.a. PMID[17081761]
NPO17823 Lycium chinense Species Solanaceae Eukaryota root bark n.a. n.a. PMID[23282106]
NPO17823 Lycium chinense Species Solanaceae Eukaryota Root Bark n.a. n.a. PMID[26982999]
NPO14267 Seseli tortuosum Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[38475524]
NPO17823 Lycium chinense Species Solanaceae Eukaryota fruits n.a. n.a. PMID[9090870]
NPO14267 Seseli tortuosum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25003 Sorocea bonplandii Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18440 Blepharostoma trichophyllum Species Pseudolepicoleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14267 Seseli tortuosum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25003 Sorocea bonplandii Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18440 Blepharostoma trichophyllum Species Pseudolepicoleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14267 Seseli tortuosum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14267 Seseli tortuosum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18509 Fissistigma oldhamii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25003 Sorocea bonplandii Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18440 Blepharostoma trichophyllum Species Pseudolepicoleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5573 Oxycoccus quadripetalus n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO14267 Seseli tortuosum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15589 Alcyonium digitatum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19046 Pyrenula pseudobufonia Species Pyrenulaceae 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 NPC59817 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
0.7632 Intermediate Similarity NPC601710
0.7564 Intermediate Similarity NPC4390
0.6912 Remote Similarity NPC183950
0.6447 Remote Similarity NPC54802
0.6447 Remote Similarity NPC197304
0.6364 Remote Similarity NPC276222
0.6364 Remote Similarity NPC274618
0.6364 Remote Similarity NPC118284
0.6364 Remote Similarity NPC608147
0.6024 Remote Similarity NPC191306
0.5952 Remote Similarity NPC197285
0.5952 Remote Similarity NPC601144
0.593 Remote Similarity NPC600989
0.5773 Remote Similarity NPC219043
0.5732 Remote Similarity NPC143851
0.5698 Remote Similarity NPC88023
0.5698 Remote Similarity NPC309025
0.5634 Remote Similarity NPC120464
0.5517 Remote Similarity NPC223747
0.5517 Remote Similarity NPC311830
0.5455 Remote Similarity NPC262699
0.5455 Remote Similarity NPC203050
0.5455 Remote Similarity NPC131217
0.5455 Remote Similarity NPC225434
0.5441 Remote Similarity NPC50898
0.5405 Remote Similarity NPC52005
0.5405 Remote Similarity NPC12200
0.5385 Remote Similarity NPC112954
0.5376 Remote Similarity NPC153755
0.5312 Remote Similarity NPC477629
0.5286 Remote Similarity NPC279121
0.5275 Remote Similarity NPC471079
0.527 Remote Similarity NPC83508
0.5234 Remote Similarity NPC192539
0.5217 Remote Similarity NPC67326
0.5205 Remote Similarity NPC231772
0.5205 Remote Similarity NPC62536
0.5205 Remote Similarity NPC483773
0.5205 Remote Similarity NPC601901
0.52 Remote Similarity NPC606638
0.5195 Remote Similarity NPC605634
0.5169 Remote Similarity NPC602805
0.5155 Remote Similarity NPC476472
0.5155 Remote Similarity NPC294815
0.5155 Remote Similarity NPC16194
0.5132 Remote Similarity NPC125062
0.5132 Remote Similarity NPC279989
0.5132 Remote Similarity NPC137062
0.507 Remote Similarity NPC274121
0.5056 Remote Similarity NPC606560
0.5054 Remote Similarity NPC66618
0.5054 Remote Similarity NPC305987

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59817 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
0.5286 Remote Similarity NPD1511 Phase 2

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