Natural Product: NPC590362

Natural Product IDNPC590362
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R})-~{N}-[2-(1~{H}-indol-3-yl)ethyl]-2-methyl-butanamide
IUPAC Name (2~{R})-~{N}-[2-(1~{H}-indol-3-yl)ethyl]-2-methyl-butanamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
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 RZZXMOMDVDHOMO-LLVKDONJSA-N
Standard InCHI InChI=1S/C15H20N2O/c1-3-11(2)15(18)16-9-8-12-10-17-14-7-5-4-6-13(12)14/h4-7,10-11,17H,3,8-9H2,1-2H3,(H,16,18)/t11-/m1/s1
SMILES CC[C@@H](C)C(=O)NCCC1=CNC2=CC=CC=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   244.16 Volume:   268.485
?
Van der Waals volume.
Dense:   0.909 LogP:   2.613
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.653
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.037
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   11.0
TPSA:   44.89
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.834 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.35 Fsp3:   0.4
MCE-18:   22.0
?
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:   0.118 Fluc inhibitor:   0.205
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.067
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.376
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.398

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.047 MDCK Permeability:   -4.71
Pgp-inhibitor:   0.116 Pgp-substrate:   0.997
PAMPA:   0.923
?
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%):   0.007 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.092

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.45 MRP1:   0.675
Plasma Protein Binding (PPB):   61.053% Volume Distribution (VD):   -0.034
Fu: 38.28%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.043
OATP1B3 inhibitor:   0.001 BCRP inhibitor:   0.069
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.974 CYP1A2-substrate:   0.81
CYP2C19-inhibitor:   0.996 CYP2C19-substrate:   0.94
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.964
CYP2D6-inhibitor:   0.873 CYP2D6-substrate:   0.895
CYP3A4-inhibitor:   0.984 CYP3A4-substrate:   0.735
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   0.934
HLM stability:   1.0
?
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):  7.527 Half-life (T1/2):  0.392

ADMET: Toxicity

hERG Blockers:  0.143 hERG Blockers (10um):  0.363
Human Hepatotoxicity (H-HT):  0.437 Drug-induced Liver Injury (DILI):  0.453
AMES Toxicity:  0.555 Rat Oral Acute Toxicity:  0.201
Maximum Recommended Daily Dose:  0.18 Skin Sensitization:  0.892
Carcinogencity:  0.316 Eye Corrosion:  0.01
Eye Irritation:  0.39 Respiratory Toxicity:  0.4
Drug-induced Neurotoxicity:  0.702 Ototoxicity:  0.551
Hematotoxicity:  0.465 Drug-induced Nephrotoxicity:  0.687
Genotoxicity:  0.939 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.01 Hek293 Cytotoxicity:  0.104
BCF:   0.412
?
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:   3.079
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.575
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.84
?
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
NPO54662 Cytophaga sp. AM13 Genus Cytophagaceae Bacteria 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

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 NPC590362 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
0.8 Intermediate Similarity NPC608269
0.7778 Intermediate Similarity NPC605381
0.7273 Intermediate Similarity NPC469760
0.7273 Intermediate Similarity NPC469786
0.6786 Remote Similarity NPC476460
0.65 Remote Similarity NPC469762
0.5902 Remote Similarity NPC611116
0.566 Remote Similarity NPC310665
0.5645 Remote Similarity NPC474561
0.5517 Remote Similarity NPC602373
0.5424 Remote Similarity NPC314002
0.5424 Remote Similarity NPC480550
0.5424 Remote Similarity NPC606242
0.5357 Remote Similarity NPC600736
0.5333 Remote Similarity NPC602670
0.5306 Remote Similarity NPC601214
0.5263 Remote Similarity NPC190296
0.5254 Remote Similarity NPC200214
0.5238 Remote Similarity NPC11126
0.5192 Remote Similarity NPC279081
0.5172 Remote Similarity NPC480551
0.5167 Remote Similarity NPC600363
0.5161 Remote Similarity NPC480548
0.5156 Remote Similarity NPC602969
0.5094 Remote Similarity NPC29886
0.5088 Remote Similarity NPC55772
0.5088 Remote Similarity NPC59269
0.5077 Remote Similarity NPC603162
0.5075 Remote Similarity NPC228835
0.5075 Remote Similarity NPC602245
0.5075 Remote Similarity NPC606412

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC590362 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
0.5091 Remote Similarity NPD786 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