Natural Product: NPC238937

Natural Product IDNPC238937
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QYBCOSRUKXCALD-GHHTXBMSSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11098414
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0001734] Pyrroloquinolines

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 QYBCOSRUKXCALD-GHHTXBMSSA-N
Standard InCHI InChI=1S/C20H26N2/c1-19(2)12-8-9-20(3)15(10-12)17(22-19)11-14-13-6-4-5-7-16(13)21-18(14)20/h4-7,12,15,17,21-22H,8-11H2,1-3H3/t12-,15+,17+,20+/m0/s1
SMILES CC1(C)[C@H]2CC[C@]3(C)[C@H](C2)[C@@H](Cc2c4ccccc4[nH]c32)N1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   294.21 Volume:   323.142
?
Van der Waals volume.
Dense:   0.91 LogP:   3.413
?
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:   -3.886
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   23.0
TPSA:   27.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.75 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.749 Fsp3:   0.6
MCE-18:   99.75
?
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:   0.48 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.443
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.44

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.938 MDCK Permeability:   -4.719
Pgp-inhibitor:   0.133 Pgp-substrate:   0.664
PAMPA:   0.134
?
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%):   0.049 30% Bioavailability (F30%):   0.152
50% Bioavailability (F50%):   0.87

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.95 MRP1:   0.721
Plasma Protein Binding (PPB):   87.325% Volume Distribution (VD):   0.624
Fu: 12.245%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.819
OATP1B3 inhibitor:   0.426 BCRP inhibitor:   0.295
BSEP inhibitor:   0.901

ADMET: Metabolism

CYP1A2-inhibitor:   0.983 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.601 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.953
CYP2D6-inhibitor:   0.976 CYP2D6-substrate:   0.333
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.007
HLM stability:   0.001
?
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):  10.814 Half-life (T1/2):  1.003

ADMET: Toxicity

hERG Blockers:  0.222 hERG Blockers (10um):  0.619
Human Hepatotoxicity (H-HT):  0.536 Drug-induced Liver Injury (DILI):  0.465
AMES Toxicity:  0.659 Rat Oral Acute Toxicity:  0.741
Maximum Recommended Daily Dose:  0.775 Skin Sensitization:  0.883
Carcinogencity:  0.567 Eye Corrosion:  0.01
Eye Irritation:  0.862 Respiratory Toxicity:  0.964
Drug-induced Neurotoxicity:  0.751 Ototoxicity:  0.616
Hematotoxicity:  0.748 Drug-induced Nephrotoxicity:  0.802
Genotoxicity:  0.564 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.563 Hek293 Cytotoxicity:  0.649
BCF:   2.702
?
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:   4.285
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.177
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.032
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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
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[11908984]
NPO19020 Salvia canariensis Species Lamiaceae Eukaryota stems and leaves n.a. n.a. PMID[19711987]
NPO13339 Aristotelia chilensis Species Elaeocarpaceae Eukaryota n.a. n.a. n.a. PMID[31276409]
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[3734816]
NPO18269 Axinyssa aplysinoides Species Halichondriidae Eukaryota n.a. n.a. n.a. PMID[7760073]
NPO19020 Salvia canariensis Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[8759159]
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8988600]
NPO18269 Axinyssa aplysinoides Species Halichondriidae Eukaryota n.a. n.a. n.a. PMID[9170294]
NPO16045 Justicia procumbens Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18269 Axinyssa aplysinoides Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13339 Aristotelia chilensis Species Elaeocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19020 Salvia canariensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18269 Axinyssa aplysinoides Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19020 Salvia canariensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13339 Aristotelia chilensis Species Elaeocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16045 Justicia procumbens Species Acanthaceae 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
NPT409 Protein complex Neuronal acetylcholine receptor; alpha4/beta2 Homo sapiens IC50 = 3400.0 nM PMID[31276409]
NPT409 Protein complex Neuronal acetylcholine receptor; alpha4/beta2 Homo sapiens Inhibition = 100.0 % PMID[31276409]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens IC50 = 27000.0 nM PMID[31276409]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens Inhibition = 100.0 % PMID[31276409]
NPT411 Protein complex Neuronal acetylcholine receptor; alpha3/beta4 Homo sapiens IC50 = 400.0 nM PMID[31276409]
NPT411 Protein complex Neuronal acetylcholine receptor; alpha3/beta4 Homo sapiens Inhibition = 100.0 % PMID[31276409]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Ratio IC50 = 8.4 n.a. PMID[31276409]
NPT2 Others Unspecified n.a. Ratio IC50 = 67.5 n.a. PMID[31276409]

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 NPC238937 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC238937 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