Natural Product: NPC605617

Natural Product IDNPC605617
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LXNQOMDRURYRCV-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL4472045
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 LXNQOMDRURYRCV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-7-2-8(17)3-10(19)15(7)14-6-12(21)16-11(20)4-9(18)5-13(16)22-14/h2-6,17-20H,1H3
SMILES Cc1cc(O)cc(O)c1-c1cc(=O)c2c(O)cc(O)cc2o1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   1.806
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.975
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.052
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   111.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.549 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.661 Fsp3:   0.062
MCE-18:   19.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.798 Fluc inhibitor:   0.678
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.91
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.506
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.536 Promiscuous compounds:   0.55

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.151 MDCK Permeability:   -4.803
Pgp-inhibitor:   0.015 Pgp-substrate:   0.679
PAMPA:   0.263
?
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):   0.002
20% Bioavailability (F20%):   0.391 30% Bioavailability (F30%):   0.836
50% Bioavailability (F50%):   0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.094 MRP1:   0.684
Plasma Protein Binding (PPB):   94.946% Volume Distribution (VD):   -0.258
Fu: 7.213%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.685
OATP1B3 inhibitor:   0.902 BCRP inhibitor:   0.935
BSEP inhibitor:   0.423

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.709
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.023
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.992
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.995
CYP3A4-inhibitor:   0.023 CYP3A4-substrate:   0.465
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.992
HLM stability:   0.914
?
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):  2.181 Half-life (T1/2):  1.628

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.523
Human Hepatotoxicity (H-HT):  0.464 Drug-induced Liver Injury (DILI):  0.522
AMES Toxicity:  0.644 Rat Oral Acute Toxicity:  0.474
Maximum Recommended Daily Dose:  0.9 Skin Sensitization:  0.679
Carcinogencity:  0.725 Eye Corrosion:  0.314
Eye Irritation:  0.999 Respiratory Toxicity:  0.867
Drug-induced Neurotoxicity:  0.044 Ototoxicity:  0.072
Hematotoxicity:  0.043 Drug-induced Nephrotoxicity:  0.027
Genotoxicity:  0.986 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.427 Hek293 Cytotoxicity:  0.874
BCF:   1.241
?
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:   3.799
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.472
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.927
?
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
NPO32511 Penicillium chrysogenum Under-species n.a. n.a. n.a. n.a. n.a. PMID[25611519]
NPO32511 Penicillium chrysogenum Under-species n.a. n.a. 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1864 Cell line L5178Y Mus musculus Activity n.a. n.a. n.a. PMID[31466836]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae Activity n.a. n.a. n.a. PMID[31466836]
NPT23810 Cell line A2780S Homo sapiens Activity n.a. n.a. n.a. PMID[31466836]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis Activity n.a. n.a. n.a. PMID[31466836]
NPT19 Organism Escherichia coli Escherichia coli Activity n.a. n.a. n.a. PMID[31466836]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus Activity n.a. n.a. n.a. PMID[31466836]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Activity n.a. n.a. n.a. PMID[31466836]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii Activity n.a. n.a. n.a. PMID[31466836]
NPT29356 Organism Klebsiella aerogenes Klebsiella aerogenes Activity n.a. n.a. n.a. PMID[31466836]
NPT1531 Organism Enterococcus faecium Enterococcus faecium Activity n.a. n.a. n.a. PMID[31466836]

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 NPC605617 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
0.6415 Remote Similarity NPC274121
0.6038 Remote Similarity NPC50898
0.6038 Remote Similarity NPC78540
0.6 Remote Similarity NPC213216
0.5926 Remote Similarity NPC175013
0.5818 Remote Similarity NPC279121
0.569 Remote Similarity NPC231772
0.569 Remote Similarity NPC62536
0.569 Remote Similarity NPC120464
0.569 Remote Similarity NPC483773
0.569 Remote Similarity NPC601901
0.5667 Remote Similarity NPC606638
0.5614 Remote Similarity NPC610974
0.5593 Remote Similarity NPC600900
0.541 Remote Similarity NPC52005
0.541 Remote Similarity NPC12200
0.5385 Remote Similarity NPC270369
0.5323 Remote Similarity NPC183950
0.5231 Remote Similarity NPC138299
0.5156 Remote Similarity NPC605634
0.5152 Remote Similarity NPC301217
0.5147 Remote Similarity NPC224714
0.5085 Remote Similarity NPC610784
0.507 Remote Similarity NPC290830

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605617 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
0.5818 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