Natural Product: NPC471638

Natural Product IDNPC471638
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 N1-Hydroxy-N5-Phenethylglutaramide
IUPAC Name N'-hydroxy-N-(2-phenylethyl)pentanediamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3086768
PubChem CID 72734543
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000331] Fatty amides
          • [CHEMONTID:0001096] N-acyl amines

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 MNMBNWINDLRVJD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H18N2O3/c16-12(7-4-8-13(17)15-18)14-10-9-11-5-2-1-3-6-11/h1-3,5-6,18H,4,7-10H2,(H,14,16)(H,15,17)
SMILES C1=CC=C(C=C1)CCNC(=O)CCCC(=O)NO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   250.13 Volume:   260.03
?
Van der Waals volume.
Dense:   0.962 LogP:   0.481
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.619
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.509
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   8.0
TPSA:   78.43
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   1.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.499 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.738 Fsp3:   0.385
MCE-18:   6.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.005 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.243
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.969

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.312 MDCK Permeability:   -4.706
Pgp-inhibitor:   0.093 Pgp-substrate:   0.955
PAMPA:   0.571
?
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):   0.004
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.025
50% Bioavailability (F50%):   0.134

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.923 MRP1:   0.133
Plasma Protein Binding (PPB):   50.115% Volume Distribution (VD):   -0.249
Fu: 44.768%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.045
OATP1B3 inhibitor:   0.042 BCRP inhibitor:   0.001
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.241
CYP2C19-inhibitor:   0.995 CYP2C19-substrate:   0.026
CYP2C9-inhibitor:   0.012 CYP2C9-substrate:   0.037
CYP2D6-inhibitor:   0.077 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.983
HLM stability:   0.784
?
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):  8.537 Half-life (T1/2):  0.936

ADMET: Toxicity

hERG Blockers:  0.215 hERG Blockers (10um):  0.244
Human Hepatotoxicity (H-HT):  0.843 Drug-induced Liver Injury (DILI):  0.064
AMES Toxicity:  0.94 Rat Oral Acute Toxicity:  0.047
Maximum Recommended Daily Dose:  0.061 Skin Sensitization:  0.997
Carcinogencity:  0.786 Eye Corrosion:  0.0
Eye Irritation:  0.017 Respiratory Toxicity:  0.112
Drug-induced Neurotoxicity:  0.047 Ototoxicity:  0.392
Hematotoxicity:  0.825 Drug-induced Nephrotoxicity:  0.888
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.004 Hek293 Cytotoxicity:  0.612
BCF:   0.372
?
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:   3.014
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.524
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.662
?
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
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[12350160]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[12762794]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. Sunday Island, Papua New Guinea n.a. PMID[18163584]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. Papua New Guinea n.a. PMID[20687534]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. Panamanian n.a. PMID[24164245]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[24588245]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[28055219]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[29808677]

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
NPT4345 Protein complex Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Homo sapiens Inhibition = 86.0 % PMID[27614919]
NPT689 Individual protein Histone deacetylase 5 Homo sapiens Inhibition = 49.0 % PMID[27614919]
NPT4345 Protein complex Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Homo sapiens Inhibition = 36.0 % PMID[27614919]
NPT689 Individual protein Histone deacetylase 5 Homo sapiens Inhibition = 0.0 % PMID[27614919]
NPT4345 Protein complex Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT689 Individual protein Histone deacetylase 5 Homo sapiens IC50 > 10000.0 nM PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens IC50 = 385.8 nM PMID[3005575]
NPT688 Individual protein Histone deacetylase 4 Homo sapiens IC50 > 1000.0 nM PMID[8230101]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens IC50 = 3.5 nM PMID[18583127]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens IC50 > 1000.0 nM PMID[27614919]
NPT684 Individual protein Histone deacetylase 1 Homo sapiens Inhibition = 86.0 % PMID[27614919]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens Inhibition = 76.0 % PMID[27614919]
NPT688 Individual protein Histone deacetylase 4 Homo sapiens Inhibition = 80.0 % PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 85.0 % PMID[27614919]
NPT690 Individual protein Histone deacetylase 7 Homo sapiens Inhibition = 47.0 % PMID[27614919]
NPT691 Individual protein Histone deacetylase 9 Homo sapiens Inhibition = 70.0 % PMID[27614919]
NPT5649 Individual protein Histone deacetylase 10 Homo sapiens Inhibition = 82.0 % PMID[27614919]
NPT684 Individual protein Histone deacetylase 1 Homo sapiens Inhibition = 31.0 % PMID[27614919]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens Inhibition = 17.0 % PMID[27614919]
NPT688 Individual protein Histone deacetylase 4 Homo sapiens Inhibition = 6.0 % PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 59.0 % PMID[27614919]
NPT690 Individual protein Histone deacetylase 7 Homo sapiens Inhibition = 29.0 % PMID[27614919]
NPT691 Individual protein Histone deacetylase 9 Homo sapiens Inhibition = 14.0 % PMID[27614919]
NPT5649 Individual protein Histone deacetylase 10 Homo sapiens Inhibition = 35.0 % PMID[27614919]
NPT684 Individual protein Histone deacetylase 1 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT688 Individual protein Histone deacetylase 4 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT690 Individual protein Histone deacetylase 7 Homo sapiens IC50 > 10000.0 nM PMID[27614919]
NPT691 Individual protein Histone deacetylase 9 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT5649 Individual protein Histone deacetylase 10 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens IC50 < 5000.0 nM PMID[27614919]
NPT687 Individual protein Histone deacetylase 8 Homo sapiens Inhibition = 70.0 % PMID[27614919]
NPT5648 Individual protein Histone deacetylase 11 Homo sapiens Inhibition = 72.0 % PMID[27614919]
NPT687 Individual protein Histone deacetylase 8 Homo sapiens Inhibition = 0.0 % PMID[27614919]
NPT5648 Individual protein Histone deacetylase 11 Homo sapiens Inhibition = 24.0 % PMID[27614919]
NPT687 Individual protein Histone deacetylase 8 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT5648 Individual protein Histone deacetylase 11 Homo sapiens IC50 = 5000.0 nM PMID[27614919]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT708 Cell line HuT78 Homo sapiens GI50 = 700.0 nM PMID[24063582]
NPT393 Cell line HCT-116 Homo sapiens GI50 = 2300.0 nM PMID[24063582]
NPT393 Cell line HCT-116 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT83 Cell line MCF7 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT708 Cell line HuT78 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT112 Cell line MOLT-4 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT927 Cell line PBMC Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT2 Others Unspecified n.a. Ratio IC50 = 110.0 n.a. PMID[8230101]

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 NPC471638 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
0.7143 Intermediate Similarity NPC600679
0.5918 Remote Similarity NPC605099
0.5909 Remote Similarity NPC601847
0.561 Remote Similarity NPC604260

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC471638 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