Natural Product: NPC46561

Natural Product IDNPC46561
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Glycozolidal
IUPAC Name 2,6-dimethoxy-9H-carbazole-3-carbaldehyde
Synonyms Glycozolidal
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2036045
PubChem CID 182690
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0000210] Carbazoles

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 WCKFRKXQABCDRE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H13NO3/c1-18-10-3-4-13-12(6-10)11-5-9(8-17)15(19-2)7-14(11)16-13/h3-8,16H,1-2H3
SMILES COc1ccc2c(c1)c1cc(C=O)c(cc1[nH]2)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   255.09 Volume:   261.239
?
Van der Waals volume.
Dense:   0.976 LogP:   2.727
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.83
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.54
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   16.0
TPSA:   51.32
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.731 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.167 Fsp3:   0.133
MCE-18:   16.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.814 Fluc inhibitor:   0.271
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.988
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.805
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.147 Promiscuous compounds:   0.673

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.785 MDCK Permeability:   -4.709
Pgp-inhibitor:   0.687 Pgp-substrate:   0.134
PAMPA:   0.09
?
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):   0.147
20% Bioavailability (F20%):   0.129 30% Bioavailability (F30%):   0.116
50% Bioavailability (F50%):   0.7

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.03 MRP1:   0.551
Plasma Protein Binding (PPB):   87.321% Volume Distribution (VD):   0.107
Fu: 10.46%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.971
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.987 CYP1A2-substrate:   0.349
CYP2C19-inhibitor:   0.833 CYP2C19-substrate:   0.091
CYP2C9-inhibitor:   0.947 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.954 CYP2D6-substrate:   0.582
CYP3A4-inhibitor:   0.027 CYP3A4-substrate:   0.265
CYP2B6-substrate:   0.483 CYP2C8-inhibitor:   0.933
HLM stability:   0.644
?
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):  8.632 Half-life (T1/2):  0.911

ADMET: Toxicity

hERG Blockers:  0.362 hERG Blockers (10um):  0.572
Human Hepatotoxicity (H-HT):  0.578 Drug-induced Liver Injury (DILI):  0.877
AMES Toxicity:  0.836 Rat Oral Acute Toxicity:  0.618
Maximum Recommended Daily Dose:  0.754 Skin Sensitization:  0.156
Carcinogencity:  0.845 Eye Corrosion:  0.009
Eye Irritation:  0.95 Respiratory Toxicity:  0.941
Drug-induced Neurotoxicity:  0.868 Ototoxicity:  0.506
Hematotoxicity:  0.56 Drug-induced Nephrotoxicity:  0.853
Genotoxicity:  0.73 RPMI-8226 Immunitoxicity:  0.172
A549 Cytotoxicity:  0.349 Hek293 Cytotoxicity:  0.566
BCF:   1.289
?
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:   3.972
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.134
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.773
?
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
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[11000023]
NPO23546 Clausena lansium Species Rutaceae Eukaryota leaves n.a. n.a. PMID[19327990]
NPO23546 Clausena lansium Species Rutaceae Eukaryota Stems n.a. n.a. PMID[22372931]
NPO23546 Clausena lansium Species Rutaceae Eukaryota Roots n.a. n.a. PMID[24798144]
NPO23546 Clausena lansium Species Rutaceae Eukaryota Leaves n.a. n.a. PMID[26523463]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[28294615]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[30970599]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23546 Clausena lansium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19266 Clausena excavata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12796 Periploca sepium Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23546 Clausena lansium Species Rutaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 4600.0 nM PMID[24798144]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[24798144]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC90 > 50000.0 nM PMID[28094223]

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 NPC46561 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
0.75 Intermediate Similarity NPC131017
0.6957 Remote Similarity NPC308137
0.6889 Remote Similarity NPC310211
0.6889 Remote Similarity NPC45190
0.6304 Remote Similarity NPC600695
0.62 Remote Similarity NPC218034
0.6122 Remote Similarity NPC300156
0.6122 Remote Similarity NPC608604
0.58 Remote Similarity NPC608975
0.5294 Remote Similarity NPC249583
0.5294 Remote Similarity NPC608740

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC46561 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