Natural Product: NPC603384

Natural Product IDNPC603384
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NHPSEEFMOLEZQR-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL239030
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 NHPSEEFMOLEZQR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H10O6/c17-11-4-9-14(5-12(11)18)20-6-10(16(9)19)8-1-2-13-15(3-8)22-7-21-13/h1-6,17-18H,7H2
SMILES O=c1c(-c2ccc3c(c2)OCO3)coc2cc(O)c(O)cc12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.05 Volume:   282.716
?
Van der Waals volume.
Dense:   1.054 LogP:   2.058
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.156
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.378
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.671 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.382 Fsp3:   0.062
MCE-18:   44.471
?
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:   1
Colloidal aggregators:   0.678 Fluc inhibitor:   0.952
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.991
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.585
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.361 Promiscuous compounds:   0.447

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.893 MDCK Permeability:   -4.712
Pgp-inhibitor:   0.017 Pgp-substrate:   0.007
PAMPA:   0.874
?
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):   0.008
20% Bioavailability (F20%):   0.381 30% Bioavailability (F30%):   0.053
50% Bioavailability (F50%):   0.93

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.063 MRP1:   0.688
Plasma Protein Binding (PPB):   92.902% Volume Distribution (VD):   -0.296
Fu: 7.231%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.752
OATP1B3 inhibitor:   0.959 BCRP inhibitor:   0.334
BSEP inhibitor:   0.966

ADMET: Metabolism

CYP1A2-inhibitor:   0.939 CYP1A2-substrate:   0.904
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.484
CYP2C9-inhibitor:   0.279 CYP2C9-substrate:   0.965
CYP2D6-inhibitor:   0.963 CYP2D6-substrate:   0.99
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.01 CYP2C8-inhibitor:   0.931
HLM stability:   0.023
?
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):  7.687 Half-life (T1/2):  1.212

ADMET: Toxicity

hERG Blockers:  0.207 hERG Blockers (10um):  0.666
Human Hepatotoxicity (H-HT):  0.5 Drug-induced Liver Injury (DILI):  0.9
AMES Toxicity:  0.717 Rat Oral Acute Toxicity:  0.562
Maximum Recommended Daily Dose:  0.818 Skin Sensitization:  0.708
Carcinogencity:  0.842 Eye Corrosion:  0.059
Eye Irritation:  0.975 Respiratory Toxicity:  0.623
Drug-induced Neurotoxicity:  0.127 Ototoxicity:  0.459
Hematotoxicity:  0.159 Drug-induced Nephrotoxicity:  0.126
Genotoxicity:  0.931 RPMI-8226 Immunitoxicity:  0.041
A549 Cytotoxicity:  0.596 Hek293 Cytotoxicity:  0.423
BCF:   1.286
?
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:   3.961
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.118
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.63
?
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
NPO48849 Mildbraediodendron excelsum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT1139 Individual protein Arachidonate 15-lipoxygenase, type II Homo sapiens IC50 > 100000.0 nM PMID[17869117]
NPT1119 Individual protein Arachidonate 12-lipoxygenase Homo sapiens IC50 > 100000.0 nM PMID[17869117]
NPT792 Individual protein Arachidonate 15-lipoxygenase Homo sapiens Activity n.a. n.a. n.a. PMID[17869117]
NPT792 Individual protein Arachidonate 15-lipoxygenase Homo sapiens IC50 > 100000.0 nM PMID[17869117]

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 NPC603384 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
0.7458 Intermediate Similarity NPC35544
0.7213 Intermediate Similarity NPC260640
0.7018 Intermediate Similarity NPC10467
0.6613 Remote Similarity NPC104728
0.65 Remote Similarity NPC148497
0.629 Remote Similarity NPC602183
0.614 Remote Similarity NPC218490
0.5873 Remote Similarity NPC12377
0.5616 Remote Similarity NPC602155
0.5538 Remote Similarity NPC602689
0.5352 Remote Similarity NPC113055
0.5224 Remote Similarity NPC110086
0.5217 Remote Similarity NPC215375
0.5161 Remote Similarity NPC195919
0.5156 Remote Similarity NPC603503
0.5152 Remote Similarity NPC200316
0.5077 Remote Similarity NPC121522
0.5077 Remote Similarity NPC209560
0.5077 Remote Similarity NPC490700

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603384 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