Natural Product: NPC237161

Natural Product IDNPC237161
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XTCGYRFLVLFRGW-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 95708
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0002374] Furanoquinolines

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 XTCGYRFLVLFRGW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H15NO5/c1-17-9-7-10(18-2)14(20-4)12-11(9)13(19-3)8-5-6-21-15(8)16-12/h5-7H,1-4H3
SMILES COc1cc(c(c2c1c(c1ccoc1n2)OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   289.1 Volume:   281.456
?
Van der Waals volume.
Dense:   1.027 LogP:   2.355
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.77
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.766
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   15.0
TPSA:   62.95
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.735 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.671 Fsp3:   0.267
MCE-18:   17.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.039 Fluc inhibitor:   0.267
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.821
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.211
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.07 Promiscuous compounds:   0.358

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.572 MDCK Permeability:   -4.6
Pgp-inhibitor:   0.562 Pgp-substrate:   0.041
PAMPA:   0.027
?
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):   0.135
20% Bioavailability (F20%):   0.136 30% Bioavailability (F30%):   0.054
50% Bioavailability (F50%):   0.494

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.016 MRP1:   0.924
Plasma Protein Binding (PPB):   86.3% Volume Distribution (VD):   -0.058
Fu: 11.657%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.926
BSEP inhibitor:   0.98

ADMET: Metabolism

CYP1A2-inhibitor:   0.951 CYP1A2-substrate:   0.181
CYP2C19-inhibitor:   0.928 CYP2C19-substrate:   0.201
CYP2C9-inhibitor:   0.972 CYP2C9-substrate:   0.065
CYP2D6-inhibitor:   0.936 CYP2D6-substrate:   0.497
CYP3A4-inhibitor:   0.818 CYP3A4-substrate:   0.079
CYP2B6-substrate:   0.834 CYP2C8-inhibitor:   0.663
HLM stability:   0.391
?
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):  7.168 Half-life (T1/2):  1.395

ADMET: Toxicity

hERG Blockers:  0.153 hERG Blockers (10um):  0.536
Human Hepatotoxicity (H-HT):  0.624 Drug-induced Liver Injury (DILI):  0.714
AMES Toxicity:  0.552 Rat Oral Acute Toxicity:  0.522
Maximum Recommended Daily Dose:  0.6 Skin Sensitization:  0.237
Carcinogencity:  0.792 Eye Corrosion:  0.009
Eye Irritation:  0.755 Respiratory Toxicity:  0.68
Drug-induced Neurotoxicity:  0.694 Ototoxicity:  0.348
Hematotoxicity:  0.62 Drug-induced Nephrotoxicity:  0.426
Genotoxicity:  0.53 RPMI-8226 Immunitoxicity:  0.142
A549 Cytotoxicity:  0.171 Hek293 Cytotoxicity:  0.38
BCF:   1.907
?
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:   3.523
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.492
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.945
?
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
NPO30937 Acronychia Genus Rutaceae Eukaryota n.a. n.a. n.a. PMID[5640105]
NPO17467 Aframomum aulacocarpos Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[7964787]
NPO2733 Sarcomelicope argyrophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO30937 Acronychia Genus Rutaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO14083 Cinnamomum oliveri Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2733 Sarcomelicope argyrophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3659 Limonium bicolor Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO766 Chlorophora excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO17467 Aframomum aulacocarpos Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18331 Agnorhiza ovata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15938 Cephalotaxus mannii Species Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30863 Zanthoxylum allanthoides Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15788 Galium aparine Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11806 Gardenia gordonii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15431 Luidia clathrata Species Luidiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17938 Plectranthus albidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13387 Senecio sundbergii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18017 Stapelia grandiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15223 Trema humbertii Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10512 Yersinia pseudotuberculosis Species Yersiniaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO766 Chlorophora excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15788 Galium aparine Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2357 Acronychia baueri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO766 Chlorophora excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2357 Acronychia baueri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15788 Galium aparine Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30863 Zanthoxylum allanthoides Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2357 Acronychia baueri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15788 Galium aparine Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11806 Gardenia gordonii Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17938 Plectranthus albidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2733 Sarcomelicope argyrophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18331 Agnorhiza ovata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17467 Aframomum aulacocarpos Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13387 Senecio sundbergii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15431 Luidia clathrata Species Luidiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18017 Stapelia grandiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14083 Cinnamomum oliveri Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15223 Trema humbertii Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10512 Yersinia pseudotuberculosis Species Yersiniaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO15788 Galium aparine Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15938 Cephalotaxus mannii Species Taxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO766 Chlorophora excelsa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO2357 Acronychia baueri Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3659 Limonium bicolor Species Plumbaginaceae 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

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 NPC237161 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
0.6818 Remote Similarity NPC203373
0.6444 Remote Similarity NPC34770
0.6 Remote Similarity NPC120513
0.5714 Remote Similarity NPC269367
0.5652 Remote Similarity NPC131885
0.5625 Remote Similarity NPC140296
0.5385 Remote Similarity NPC208364
0.5283 Remote Similarity NPC173250
0.5179 Remote Similarity NPC600693
0.5179 Remote Similarity NPC605376
0.5098 Remote Similarity NPC160100
0.5088 Remote Similarity NPC166712

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC237161 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