Natural Product: NPC4687

Natural Product IDNPC4687
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Clausine C
IUPAC Name methyl 7-methoxy-9H-carbazole-3-carboxylate
Synonyms Clausine C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1173128
PubChem CID 11817681
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 UHYHEIKZOWURQD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H13NO3/c1-18-10-4-5-11-12-7-9(15(17)19-2)3-6-13(12)16-14(11)8-10/h3-8,16H,1-2H3
SMILES COc1ccc2c(c1)[nH]c1c2cc(cc1)C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   255.09 Volume:   261.239
?
Van der Waals volume.
Dense:   0.976 LogP:   3.601
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.225
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.048
?
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:   0.716 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.861 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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.386 Fluc inhibitor:   0.92
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.977
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.494
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.149 Promiscuous compounds:   0.962

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.731 MDCK Permeability:   -4.481
Pgp-inhibitor:   0.733 Pgp-substrate:   0.208
PAMPA:   0.142
?
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):   0.025
20% Bioavailability (F20%):   0.114 30% Bioavailability (F30%):   0.11
50% Bioavailability (F50%):   0.832

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.976
Plasma Protein Binding (PPB):   98.114% Volume Distribution (VD):   0.071
Fu: 1.441%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.966
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.967
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.721 CYP1A2-substrate:   0.986
CYP2C19-inhibitor:   0.302 CYP2C19-substrate:   0.162
CYP2C9-inhibitor:   0.826 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.95 CYP2D6-substrate:   0.111
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.01
CYP2B6-substrate:   0.054 CYP2C8-inhibitor:   0.999
HLM stability:   0.998
?
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):  9.077 Half-life (T1/2):  0.738

ADMET: Toxicity

hERG Blockers:  0.369 hERG Blockers (10um):  0.651
Human Hepatotoxicity (H-HT):  0.295 Drug-induced Liver Injury (DILI):  0.959
AMES Toxicity:  0.813 Rat Oral Acute Toxicity:  0.571
Maximum Recommended Daily Dose:  0.726 Skin Sensitization:  0.073
Carcinogencity:  0.862 Eye Corrosion:  0.0
Eye Irritation:  0.928 Respiratory Toxicity:  0.833
Drug-induced Neurotoxicity:  0.854 Ototoxicity:  0.561
Hematotoxicity:  0.244 Drug-induced Nephrotoxicity:  0.766
Genotoxicity:  0.627 RPMI-8226 Immunitoxicity:  0.168
A549 Cytotoxicity:  0.277 Hek293 Cytotoxicity:  0.589
BCF:   1.019
?
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:   3.82
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.913
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.439
?
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
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[11720530]
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[16724858]
NPO29161 Hyptis urticoides Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19265396]
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. Guam Island, Pacific Ocean n.a. PMID[21774474]
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[22050382]
NPO4806 Clausena wallichii Species Rutaceae Eukaryota Roots n.a. n.a. PMID[22482432]
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. Guam Island, Pacific Ocean n.a. PMID[23164710]
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[26203536]
NPO24890 Iris sanguinea Species Iridaceae Eukaryota Seeds n.a. n.a. PMID[28951079]
NPO24890 Iris sanguinea Species Iridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29161 Hyptis urticoides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29073 Ipomoea carnea Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29028 Cicer cuneatum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28961 Croton hutchinsonianus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28943 Daldinia vernicosa Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29461 Sarcophyton infundibuliforme Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29035 Pseudomonas cichorii Species Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO24890 Iris sanguinea Species Iridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24890 Iris sanguinea Species Iridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28500 Griselinia scandens Species Griseliniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23710 Otholobium pubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4806 Clausena wallichii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29070 Bulbine asphodeloides Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28993 Streptomyces venezuelae Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO28544 Podocalyx loranthoides Species Picrodendraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24890 Iris sanguinea Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25073 Saccharina latissima Species Laminariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29497 Delphinium speciosum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28427 Gutenbergia marginata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27349 Rhododendron edgeworthii Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25248 Gloydius blomhoffii Species Viperidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29073 Ipomoea carnea Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29518 Nardia scalaris Species Solenostomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29180 Monachosorum maximowiczii Species Dennstaedtiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28961 Croton hutchinsonianus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29095 Yucca elata Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29161 Hyptis urticoides Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29321 Octopus octopodia Species Octopodidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29028 Cicer cuneatum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27603 Populus candicans Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28735 Helicia erratica Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29461 Sarcophyton infundibuliforme Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29387 Eudendrium racemosum Species Eudendriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28639 Trixis grisebachii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29035 Pseudomonas cichorii Species Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO28943 Daldinia vernicosa Species Xylariaceae 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
NPT832 Individual protein Kinesin-like protein 1 Homo sapiens Inhibition = 15.0 % PMID[20521839]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC = 128.0 ug.mL-1 PMID[22482432]
NPT790 Organism Mycobacterium tuberculosis H37Rv Mycobacterium tuberculosis H37Rv MIC90 > 128000.0 nM DOI[10.1007/s00044-007-9073-0]

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 NPC4687 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
0.7083 Intermediate Similarity NPC300156
0.6875 Remote Similarity NPC249583
0.6875 Remote Similarity NPC169402
0.6809 Remote Similarity NPC160381
0.6122 Remote Similarity NPC310211
0.6038 Remote Similarity NPC39679
0.566 Remote Similarity NPC116238
0.5273 Remote Similarity NPC247803
0.5179 Remote Similarity NPC39500
0.5179 Remote Similarity NPC87413

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC4687 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