Natural Product: NPC162484

Natural Product IDNPC162484
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Koenimbine
IUPAC Name 8-methoxy-3,3,5-trimethyl-11H-pyrano[3,2-a]carbazole
Synonyms Koenimbine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2323768
PubChem CID 97487
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 OSERHKINMDLESD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H19NO2/c1-11-9-15-14-10-12(21-4)5-6-16(14)20-17(15)13-7-8-19(2,3)22-18(11)13/h5-10,20H,1-4H3
SMILES COc1ccc2c(c1)c1cc(C)c3c(c1[nH]2)C=CC(O3)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   293.14 Volume:   313.076
?
Van der Waals volume.
Dense:   0.936 LogP:   4.903
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.952
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.128
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   34.25
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.698 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.71 Fsp3:   0.263
MCE-18:   47.917
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.906 Fluc inhibitor:   0.49
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.956
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.694
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.067 Promiscuous compounds:   0.653

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.805 MDCK Permeability:   -4.658
Pgp-inhibitor:   0.786 Pgp-substrate:   0.125
PAMPA:   0.087
?
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):   0.011
20% Bioavailability (F20%):   0.15 30% Bioavailability (F30%):   0.239
50% Bioavailability (F50%):   0.89

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.407 MRP1:   0.822
Plasma Protein Binding (PPB):   98.172% Volume Distribution (VD):   0.301
Fu: 1.328%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.929
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.956 CYP1A2-substrate:   0.763
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.093
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.754
CYP2D6-inhibitor:   0.993 CYP2D6-substrate:   0.725
CYP3A4-inhibitor:   0.018 CYP3A4-substrate:   0.247
CYP2B6-substrate:   0.558 CYP2C8-inhibitor:   0.999
HLM stability:   0.947
?
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):  8.122 Half-life (T1/2):  0.506

ADMET: Toxicity

hERG Blockers:  0.463 hERG Blockers (10um):  0.636
Human Hepatotoxicity (H-HT):  0.69 Drug-induced Liver Injury (DILI):  0.877
AMES Toxicity:  0.859 Rat Oral Acute Toxicity:  0.718
Maximum Recommended Daily Dose:  0.826 Skin Sensitization:  0.15
Carcinogencity:  0.896 Eye Corrosion:  0.0
Eye Irritation:  0.799 Respiratory Toxicity:  0.958
Drug-induced Neurotoxicity:  0.903 Ototoxicity:  0.665
Hematotoxicity:  0.598 Drug-induced Nephrotoxicity:  0.876
Genotoxicity:  0.351 RPMI-8226 Immunitoxicity:  0.169
A549 Cytotoxicity:  0.389 Hek293 Cytotoxicity:  0.591
BCF:   2.283
?
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:   4.391
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.381
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.896
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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
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[12662104]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. Sri Lankan n.a. PMID[23376010]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota fruits Coimbatore, India 2010-JUN PMID[23691929]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[27136692]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[39414752]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3364 Murraya koenigii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3364 Murraya koenigii 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
NPT2797 Individual protein Pancreatic lipase Homo sapiens IC50 = 168600.0 nM PMID[27908755]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 4.3 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 1.0 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = -0.1 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = -1.0 % PMID[23376010]
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 0.7 % PMID[23376010]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT377 Cell line OVCAR-3 Homo sapiens IC50 = 200.0 nM PMID[34838335]
NPT65 Cell line HepG2 Homo sapiens IC50 = 200.0 nM PMID[34838335]
NPT90 Cell line DU-145 Homo sapiens IC50 = 200.0 nM PMID[34838335]
NPT2400 Cell line PA-1 Homo sapiens IC50 = 200.0 nM PMID[34838335]
NPT165 Cell line HeLa Homo sapiens IC50 = 200.0 nM PMID[34838335]
NPT393 Cell line HCT-116 Homo sapiens IC50 = 200.0 nM PMID[34838335]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 15.5 % PMID[27136692]
NPT610 Others Molecular identity unknown n.a. FC = 1.44 n.a. PMID[27136692]
NPT610 Others Molecular identity unknown n.a. FC = 1.41 n.a. PMID[27136692]
NPT610 Others Molecular identity unknown n.a. FC = 2.54 n.a. PMID[27136692]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 19.8 % PMID[27136692]
NPT2 Others Unspecified n.a. IC50 = 1200.0 nM PMID[23376010]
NPT2 Others Unspecified n.a. Inhibition = 86.2 % PMID[23376010]
NPT2 Others Unspecified n.a. Inhibition = 77.0 % PMID[23376010]
NPT2 Others Unspecified n.a. Inhibition = 42.5 % PMID[23376010]

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 NPC162484 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
0.7321 Intermediate Similarity NPC99417
0.7193 Intermediate Similarity NPC64751
0.6964 Remote Similarity NPC43787
0.65 Remote Similarity NPC201697
0.6129 Remote Similarity NPC277351
0.5942 Remote Similarity NPC484122
0.5942 Remote Similarity NPC484119
0.5873 Remote Similarity NPC198503
0.5556 Remote Similarity NPC209769
0.5493 Remote Similarity NPC484120
0.5286 Remote Similarity NPC72211
0.5263 Remote Similarity NPC131017
0.5263 Remote Similarity NPC484123
0.5132 Remote Similarity NPC484115
0.5132 Remote Similarity NPC484114
0.5072 Remote Similarity NPC205934
0.5072 Remote Similarity NPC267766

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC162484 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