Natural Product: NPC478812

Natural Product IDNPC478812
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MONOMZXDURAAAV-BKCMZVEJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 127031267
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0001097] Benzyloxycarbonyls

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 MONOMZXDURAAAV-BKCMZVEJSA-N
Standard InCHI InChI=1S/C20H31ClO4/c1-4-5-9-17(21)10-7-6-8-14(2)20(25-15(3)22)16-11-18(23)13-19(24)12-16/h11-14,17,20,23-24H,4-10H2,1-3H3/t14-,17?,20+/m0/s1
SMILES CCCCC(CCCC[C@H](C)[C@H](c1cc(cc(c1)O)O)OC(=O)C)Cl

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.19 Volume:   385.746
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Van der Waals volume.
Dense:   0.96 LogP:   4.473
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.785
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.587
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   7.0
TPSA:   66.76
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.298 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.634 Fsp3:   0.65
MCE-18:   20.0
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.384 Fluc inhibitor:   0.06
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.033
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.685 Promiscuous compounds:   0.114

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.112 MDCK Permeability:   -4.659
Pgp-inhibitor:   0.002 Pgp-substrate:   0.011
PAMPA:   0.012
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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):   0.0
20% Bioavailability (F20%):   0.798 30% Bioavailability (F30%):   0.943
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.036 MRP1:   0.936
Plasma Protein Binding (PPB):   98.009% Volume Distribution (VD):   0.387
Fu: 2.515%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.857
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.388
BSEP inhibitor:   0.261

ADMET: Metabolism

CYP1A2-inhibitor:   0.018 CYP1A2-substrate:   0.893
CYP2C19-inhibitor:   0.345 CYP2C19-substrate:   0.179
CYP2C9-inhibitor:   0.419 CYP2C9-substrate:   0.102
CYP2D6-inhibitor:   0.05 CYP2D6-substrate:   0.864
CYP3A4-inhibitor:   0.062 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.352
?
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):  6.568 Half-life (T1/2):  0.752

ADMET: Toxicity

hERG Blockers:  0.279 hERG Blockers (10um):  0.623
Human Hepatotoxicity (H-HT):  0.491 Drug-induced Liver Injury (DILI):  0.052
AMES Toxicity:  0.153 Rat Oral Acute Toxicity:  0.105
Maximum Recommended Daily Dose:  0.303 Skin Sensitization:  0.966
Carcinogencity:  0.344 Eye Corrosion:  0.769
Eye Irritation:  0.996 Respiratory Toxicity:  0.405
Drug-induced Neurotoxicity:  0.028 Ototoxicity:  0.249
Hematotoxicity:  0.059 Drug-induced Nephrotoxicity:  0.044
Genotoxicity:  0.004 RPMI-8226 Immunitoxicity:  0.034
A549 Cytotoxicity:  0.146 Hek293 Cytotoxicity:  0.404
BCF:   1.826
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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:   4.654
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.848
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.428
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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
NPO40250 Nostoc sp. CAVN2 Strain Nostocaceae Bacteria n.a. n.a. n.a. PMID[26684177]

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
NPT941 Cell line HaCaT Homo sapiens IC50 = 100000.0 nM PMID[26684177]
NPT1118 Organism Streptococcus pneumoniae Streptococcus pneumoniae MIC = 17000.0 nM PMID[26684177]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC > 135000.0 nM PMID[26684177]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 8600.0 nM PMID[26684177]
NPT19 Organism Escherichia coli Escherichia coli MIC > 135000.0 nM PMID[26684177]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 135000.0 nM PMID[26684177]

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 NPC478812 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
0.7818 Intermediate Similarity NPC478814
0.6719 Remote Similarity NPC478813
0.5455 Remote Similarity NPC257947

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC478812 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