Natural Product: NPC96901

Natural Product IDNPC96901
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Icajine
IUPAC Name n.a.
Synonyms Icajine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2164624
PubChem CID 3083907
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 RNZRHJNFQWMXHB-ZXXLSYNSSA-N
Standard InCHI InChI=1S/C22H24N2O3/c1-23-8-7-22-15-4-2-3-5-16(15)24-19(26)11-17-20(21(22)24)14(10-18(22)25)13(12-23)6-9-27-17/h2-6,14,17,20-21H,7-12H2,1H3/t14-,17-,20-,21-,22+/m0/s1
SMILES CN1CC[C@]23C(=O)C[C@H]4C(=CCO[C@@H]5[C@H]4[C@@H]3N(c3c2cccc3)C(=O)C5)C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   364.18 Volume:   370.275
?
Van der Waals volume.
Dense:   0.984 LogP:   1.386
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.681
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.614
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   31.0
TPSA:   49.85
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   7.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.66 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.401 Fsp3:   0.545
MCE-18:   148.706
?
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:   0.362 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.045
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.396
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.519

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.602 MDCK Permeability:   -4.831
Pgp-inhibitor:   0.12 Pgp-substrate:   0.772
PAMPA:   0.037
?
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%):   0.001 30% Bioavailability (F30%):   0.226
50% Bioavailability (F50%):   0.898

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.972 MRP1:   0.451
Plasma Protein Binding (PPB):   25.372% Volume Distribution (VD):   0.306
Fu: 66.419%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.021
BSEP inhibitor:   0.783

ADMET: Metabolism

CYP1A2-inhibitor:   0.732 CYP1A2-substrate:   0.016
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.059 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.204
CYP3A4-inhibitor:   0.995 CYP3A4-substrate:   0.089
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.002
HLM stability:   0.621
?
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):  8.212 Half-life (T1/2):  2.859

ADMET: Toxicity

hERG Blockers:  0.114 hERG Blockers (10um):  0.422
Human Hepatotoxicity (H-HT):  0.853 Drug-induced Liver Injury (DILI):  0.581
AMES Toxicity:  0.375 Rat Oral Acute Toxicity:  0.467
Maximum Recommended Daily Dose:  0.459 Skin Sensitization:  0.982
Carcinogencity:  0.498 Eye Corrosion:  0.001
Eye Irritation:  0.07 Respiratory Toxicity:  0.661
Drug-induced Neurotoxicity:  0.796 Ototoxicity:  0.586
Hematotoxicity:  0.87 Drug-induced Nephrotoxicity:  0.878
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.021
A549 Cytotoxicity:  0.014 Hek293 Cytotoxicity:  0.174
BCF:   0.486
?
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:   3.151
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.66
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.916
?
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
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. leaf n.a. DOI[10.1016/0040-4020(73)80248-0]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[10.1016/j.tet.2012.03.006]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. DOI[10.1016/j.tet.2012.03.006]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[11170658]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. root n.a. PMID[11170658]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[12398531]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. root n.a. PMID[12560037]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[16317898]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[17449162]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[19235686]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota Root bark Central Africa n.a. PMID[19299148]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[19666019]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[22707864]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[23088673]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[2393954]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota Roots n.a. n.a. PMID[24593048]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[25594733]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[25594733]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. leaf n.a. PMID[4954818]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. seed n.a. PMID[7912074]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28245 Strychnos nux-vomica Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4386 Strychnos icaja Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28245 Strychnos nux-vomica Species Loganiaceae 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
NPT660 Cell line SW480 Homo sapiens IC50 > 40000.0 nM PMID[23088673]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[23088673]
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PMID[23088673]
NPT659 Cell line SMMC-7721 Homo sapiens IC50 > 40000.0 nM PMID[23088673]
NPT116 Cell line HL-60 Homo sapiens IC50 > 40000.0 nM PMID[23088673]

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 NPC96901 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
0.76 Intermediate Similarity NPC306552
0.7568 Intermediate Similarity NPC10732
0.7297 Intermediate Similarity NPC485857
0.6154 Remote Similarity NPC214626
0.6154 Remote Similarity NPC251212
0.6154 Remote Similarity NPC198901
0.6154 Remote Similarity NPC139085
0.6 Remote Similarity NPC22689
0.6 Remote Similarity NPC105055
0.5783 Remote Similarity NPC485154
0.5556 Remote Similarity NPC11149
0.5233 Remote Similarity NPC138830

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC96901 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