Natural Product: NPC604356

Natural Product IDNPC604356
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KPYQJVYNSWDFQU-ORXIWHNOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1215040
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 KPYQJVYNSWDFQU-ORXIWHNOSA-N
Standard InCHI InChI=1S/C16H20O8/c1-22-12(18)7-4-9-2-5-10(6-3-9)23-16-15(21)14(20)13(19)11(8-17)24-16/h2-7,11,13-17,19-21H,8H2,1H3/b7-4+/t11-,13-,14+,15-,16-/m1/s1
SMILES COC(=O)/C=C/c1ccc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.12 Volume:   325.319
?
Van der Waals volume.
Dense:   1.045 LogP:   0.512
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.072
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.777
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   14.0
TPSA:   125.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.399 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.48 Fsp3:   0.438
MCE-18:   48.087
?
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:   0.742 Fluc inhibitor:   0.901
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.284
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.191
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.293 Promiscuous compounds:   0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.704 MDCK Permeability:   -5.096
Pgp-inhibitor:   0.122 Pgp-substrate:   0.018
PAMPA:   0.92
?
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):   0.826
20% Bioavailability (F20%):   0.907 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.0
Plasma Protein Binding (PPB):   72.08% Volume Distribution (VD):   -0.409
Fu: 26.91%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.236
BSEP inhibitor:   0.711

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.114
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.001
?
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):  2.588 Half-life (T1/2):  2.628

ADMET: Toxicity

hERG Blockers:  0.031 hERG Blockers (10um):  0.104
Human Hepatotoxicity (H-HT):  0.631 Drug-induced Liver Injury (DILI):  0.896
AMES Toxicity:  0.91 Rat Oral Acute Toxicity:  0.021
Maximum Recommended Daily Dose:  0.035 Skin Sensitization:  0.994
Carcinogencity:  0.279 Eye Corrosion:  0.0
Eye Irritation:  0.41 Respiratory Toxicity:  0.009
Drug-induced Neurotoxicity:  0.02 Ototoxicity:  0.868
Hematotoxicity:  0.26 Drug-induced Nephrotoxicity:  0.814
Genotoxicity:  0.16 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.078 Hek293 Cytotoxicity:  0.123
BCF:   0.755
?
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:   3.38
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.049
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.387
?
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
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[32141299]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26277 Euphorbia hirta Species Euphorbiaceae 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
NPT1293 Individual protein Tyrosine-protein kinase SYK Rattus norvegicus Inhibition n.a. n.a. % PMID[20663674]

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 NPC604356 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
0.78 Intermediate Similarity NPC200092
0.7679 Intermediate Similarity NPC100389
0.7119 Intermediate Similarity NPC185778
0.6786 Remote Similarity NPC251102
0.6786 Remote Similarity NPC210298
0.6562 Remote Similarity NPC186406
0.6557 Remote Similarity NPC202700
0.6471 Remote Similarity NPC212729
0.6471 Remote Similarity NPC604498
0.6346 Remote Similarity NPC269242
0.6296 Remote Similarity NPC60589
0.6296 Remote Similarity NPC469708
0.6296 Remote Similarity NPC609376
0.6226 Remote Similarity NPC294470
0.6207 Remote Similarity NPC479028
0.6207 Remote Similarity NPC479031
0.6102 Remote Similarity NPC26080
0.6102 Remote Similarity NPC165686
0.6102 Remote Similarity NPC481303
0.6056 Remote Similarity NPC476867
0.6 Remote Similarity NPC259767
0.6 Remote Similarity NPC248355
0.5902 Remote Similarity NPC55040
0.5806 Remote Similarity NPC302378
0.5789 Remote Similarity NPC80098
0.5781 Remote Similarity NPC37468
0.5781 Remote Similarity NPC186418
0.5738 Remote Similarity NPC479029
0.5714 Remote Similarity NPC145319
0.5714 Remote Similarity NPC166180
0.5714 Remote Similarity NPC157554
0.5694 Remote Similarity NPC93924
0.5652 Remote Similarity NPC488085
0.5636 Remote Similarity NPC153149
0.5625 Remote Similarity NPC294166
0.5625 Remote Similarity NPC115022
0.5593 Remote Similarity NPC11724
0.5574 Remote Similarity NPC210478
0.5556 Remote Similarity NPC142319
0.5526 Remote Similarity NPC475213
0.5526 Remote Similarity NPC152796
0.5522 Remote Similarity NPC295970
0.5522 Remote Similarity NPC57587
0.55 Remote Similarity NPC218685
0.55 Remote Similarity NPC49074
0.5441 Remote Similarity NPC601944
0.5432 Remote Similarity NPC600083
0.5432 Remote Similarity NPC600336
0.5417 Remote Similarity NPC292443
0.541 Remote Similarity NPC162093
0.5405 Remote Similarity NPC199928
0.5385 Remote Similarity NPC228907
0.5373 Remote Similarity NPC248119
0.5373 Remote Similarity NPC98777
0.5333 Remote Similarity NPC310661
0.5325 Remote Similarity NPC475379
0.5312 Remote Similarity NPC59324
0.5312 Remote Similarity NPC232673
0.5312 Remote Similarity NPC34456
0.5303 Remote Similarity NPC479030
0.5286 Remote Similarity NPC291153
0.5273 Remote Similarity NPC276195
0.5263 Remote Similarity NPC25817
0.5263 Remote Similarity NPC476866
0.5256 Remote Similarity NPC478985
0.5254 Remote Similarity NPC221090
0.5246 Remote Similarity NPC232880
0.5231 Remote Similarity NPC470236
0.5231 Remote Similarity NPC146540
0.5224 Remote Similarity NPC474044
0.5217 Remote Similarity NPC606353
0.5179 Remote Similarity NPC217854
0.5179 Remote Similarity NPC484157
0.5172 Remote Similarity NPC604439
0.5167 Remote Similarity NPC166040
0.5161 Remote Similarity NPC270849
0.5161 Remote Similarity NPC19470
0.5156 Remote Similarity NPC104167
0.5139 Remote Similarity NPC310064
0.5132 Remote Similarity NPC476864
0.5122 Remote Similarity NPC469654
0.5088 Remote Similarity NPC192810
0.5085 Remote Similarity NPC226712
0.5085 Remote Similarity NPC608788
0.5082 Remote Similarity NPC9912
0.5079 Remote Similarity NPC214910
0.5075 Remote Similarity NPC8497
0.5075 Remote Similarity NPC604095
0.5072 Remote Similarity NPC264381
0.507 Remote Similarity NPC185103
0.5068 Remote Similarity NPC232228
0.5065 Remote Similarity NPC476869
0.5063 Remote Similarity NPC253595
0.5063 Remote Similarity NPC26928
0.5063 Remote Similarity NPC476865

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604356 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
0.5085 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