Natural Product: NPC82053

Natural Product IDNPC82053
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl 6-Bromo-1H-Indole-3-Carboxylate
IUPAC Name methyl 6-bromo-1H-indole-3-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL457164
PubChem CID 11499811
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002013] Indolecarboxylic acids and derivatives

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 SKZJYJMYLUQJPG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C10H8BrNO2/c1-14-10(13)8-5-12-9-4-6(11)2-3-7(8)9/h2-5,12H,1H3
SMILES COC(=O)c1c[nH]c2c1ccc(c2)Br

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   252.97 Volume:   199.082
?
Van der Waals volume.
Dense:   1.271 LogP:   3.406
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.064
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.65
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   11.0
TPSA:   42.09
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.795 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.995 Fsp3:   0.1
MCE-18:   11.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.415 Fluc inhibitor:   0.023
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.108
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.43
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.321 Promiscuous compounds:   0.887

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.65 MDCK Permeability:   -4.703
Pgp-inhibitor:   0.917 Pgp-substrate:   0.037
PAMPA:   0.094
?
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):   0.001
20% Bioavailability (F20%):   0.025 30% Bioavailability (F30%):   0.091
50% Bioavailability (F50%):   0.229

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.962 MRP1:   0.997
Plasma Protein Binding (PPB):   97.86% Volume Distribution (VD):   0.099
Fu: 1.433%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.959
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.504
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.059 CYP1A2-substrate:   0.956
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.495
CYP2C9-inhibitor:   0.215 CYP2C9-substrate:   0.881
CYP2D6-inhibitor:   0.953 CYP2D6-substrate:   0.973
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.534
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.896
?
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):  8.394 Half-life (T1/2):  1.013

ADMET: Toxicity

hERG Blockers:  0.119 hERG Blockers (10um):  0.548
Human Hepatotoxicity (H-HT):  0.39 Drug-induced Liver Injury (DILI):  0.795
AMES Toxicity:  0.367 Rat Oral Acute Toxicity:  0.483
Maximum Recommended Daily Dose:  0.632 Skin Sensitization:  0.546
Carcinogencity:  0.581 Eye Corrosion:  0.697
Eye Irritation:  0.992 Respiratory Toxicity:  0.403
Drug-induced Neurotoxicity:  0.616 Ototoxicity:  0.243
Hematotoxicity:  0.227 Drug-induced Nephrotoxicity:  0.274
Genotoxicity:  0.608 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.055 Hek293 Cytotoxicity:  0.111
BCF:   0.978
?
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:   3.669
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.965
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.434
?
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
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.tet.2007.03.162]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.tet.2008.05.037]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.tet.2008.10.076]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[10075778]
NPO33153 thorectandra sp. Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[11374971]
NPO33153 thorectandra sp. Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[11975486]
NPO32965 smenospongia sp. Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[15497955]
NPO33153 thorectandra sp. Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[16252912]
NPO32965 smenospongia sp. Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[16252912]
NPO32965 smenospongia sp. Species Thorectidae Eukaryota n.a. n.a. n.a. PMID[18973387]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. Fiji (S 1822.28', E 17758.87') 2000-FEB PMID[21241058]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[21241058]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[26883470]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11484 Jaspis splendens Species Ancorinidae Eukaryota n.a. n.a. n.a. Database[UNPD]

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
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 50.0 ug.mL-1 PMID[26443078]

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 NPC82053 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
0.6591 Remote Similarity NPC608580
0.6512 Remote Similarity NPC110158
0.6512 Remote Similarity NPC601116
0.625 Remote Similarity NPC88315
0.5909 Remote Similarity NPC138370
0.5882 Remote Similarity NPC233050
0.5882 Remote Similarity NPC276540
0.56 Remote Similarity NPC489192
0.5417 Remote Similarity NPC601285
0.5273 Remote Similarity NPC275292
0.5273 Remote Similarity NPC243381
0.52 Remote Similarity NPC603023
0.5185 Remote Similarity NPC606242
0.5098 Remote Similarity NPC141926

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC82053 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