Natural Product: NPC602125

Natural Product IDNPC602125
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WRFQRUBJBPLPAM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL509256
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 WRFQRUBJBPLPAM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-21-13-6-8(2-5-11(13)18)16-15(20)14(19)10-4-3-9(17)7-12(10)22-16/h2-7,17-18,20H,1H3
SMILES COc1cc(-c2oc3cc(O)ccc3c(=O)c2O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   1.66
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.834
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.779
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.672 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.271 Fsp3:   0.062
MCE-18:   18.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.703 Fluc inhibitor:   0.947
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.983
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.688
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.559 Promiscuous compounds:   0.859

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.218 MDCK Permeability:   -4.807
Pgp-inhibitor:   0.773 Pgp-substrate:   0.119
PAMPA:   0.207
?
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):   0.3
20% Bioavailability (F20%):   0.201 30% Bioavailability (F30%):   0.869
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.543
Plasma Protein Binding (PPB):   97.184% Volume Distribution (VD):   -0.712
Fu: 2.57%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.984
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.998
BSEP inhibitor:   0.932

ADMET: Metabolism

CYP1A2-inhibitor:   0.718 CYP1A2-substrate:   0.517
CYP2C19-inhibitor:   0.007 CYP2C19-substrate:   0.822
CYP2C9-inhibitor:   0.131 CYP2C9-substrate:   0.09
CYP2D6-inhibitor:   0.909 CYP2D6-substrate:   0.984
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.883
?
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):  5.046 Half-life (T1/2):  1.752

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.493
Human Hepatotoxicity (H-HT):  0.4 Drug-induced Liver Injury (DILI):  0.693
AMES Toxicity:  0.604 Rat Oral Acute Toxicity:  0.449
Maximum Recommended Daily Dose:  0.668 Skin Sensitization:  0.676
Carcinogencity:  0.762 Eye Corrosion:  0.753
Eye Irritation:  0.997 Respiratory Toxicity:  0.738
Drug-induced Neurotoxicity:  0.088 Ototoxicity:  0.106
Hematotoxicity:  0.103 Drug-induced Nephrotoxicity:  0.052
Genotoxicity:  0.801 RPMI-8226 Immunitoxicity:  0.058
A549 Cytotoxicity:  0.233 Hek293 Cytotoxicity:  0.568
BCF:   1.095
?
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:   3.542
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.242
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.779
?
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
NPO25265 Sophora secundiflora Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0040-4039(00)78784-3]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota Leaves n.a. n.a. PMID[17637068]
NPO61859 Anthyllis vulneraria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21447 Lotus corniculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO194 Tetragonolobus siliquosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25265 Sophora secundiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19488 Trifolium subterraneum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19488 Trifolium subterraneum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21447 Lotus corniculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19488 Trifolium subterraneum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21447 Lotus corniculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21447 Lotus corniculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21447 Lotus corniculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13278 Strychnos spinosa Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO194 Tetragonolobus siliquosus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25265 Sophora secundiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19488 Trifolium subterraneum Species Fabaceae 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
NPT1226 Individual protein Caspase-7 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT1626 Individual protein Protein E6 Human papillomavirus type 16 Inhibition n.a. n.a. % PMID[22300659]
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT1380 Individual protein Avian myoblastosis virus polyprotein II Avian myeloblastosis virus Inhibition = 52.7 % DOI[10.1007/s00044-011-9570-z]
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 19952.6 nM PubChem BioAssay data set
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT277 Individual protein Caspase-1 Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT282 Individual protein MAP kinase ERK2 Homo sapiens Potency = 7943.3 nM PubChem BioAssay data set
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 20596.2 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 31622.8 nM PubChem BioAssay data set
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = 12.76 % PMID[23062825]
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 5011.9 nM PubChem BioAssay data set
NPT792 Individual protein Arachidonate 15-lipoxygenase Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = 3.26 % PMID[23062825]
NPT583 Individual protein Inositol monophosphatase 1 Rattus norvegicus Potency = 28183.8 nM PubChem BioAssay data set
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 19952.6 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 7943.3 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 2511.9 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 794.3 nM PubChem BioAssay data set
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 2511.9 nM PubChem BioAssay data set
NPT442 Individual protein Ferritin light chain Equus caballus Potency = 35481.3 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency = 31622.8 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency = 15848.9 nM PubChem BioAssay data set
NPT30063 Cell line Monocyte Homo sapiens IC50 = 2300.0 nM PMID[8882428]
NPT29533 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT29533 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 14125.4 nM PubChem BioAssay data set

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 NPC602125 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
0.7636 Intermediate Similarity NPC55205
0.7273 Intermediate Similarity NPC281207
0.7193 Intermediate Similarity NPC115323
0.7069 Intermediate Similarity NPC125062
0.7069 Intermediate Similarity NPC604021
0.6792 Remote Similarity NPC51443
0.65 Remote Similarity NPC252933
0.6481 Remote Similarity NPC299379
0.6393 Remote Similarity NPC227192
0.6071 Remote Similarity NPC74881
0.6066 Remote Similarity NPC610401
0.6 Remote Similarity NPC269652
0.5763 Remote Similarity NPC136840
0.5738 Remote Similarity NPC312924
0.5645 Remote Similarity NPC602344
0.5574 Remote Similarity NPC260895
0.5556 Remote Similarity NPC236223
0.5556 Remote Similarity NPC604422
0.5556 Remote Similarity NPC607642
0.5469 Remote Similarity NPC183950
0.5469 Remote Similarity NPC279989
0.5469 Remote Similarity NPC139364
0.5323 Remote Similarity NPC28274
0.5323 Remote Similarity NPC270465
0.5323 Remote Similarity NPC266597
0.5323 Remote Similarity NPC605146
0.5256 Remote Similarity NPC206123
0.5161 Remote Similarity NPC98661
0.5156 Remote Similarity NPC54394
0.5156 Remote Similarity NPC50728
0.5156 Remote Similarity NPC83508
0.5156 Remote Similarity NPC159103
0.5156 Remote Similarity NPC20830
0.5147 Remote Similarity NPC269906
0.5079 Remote Similarity NPC143799

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602125 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