Natural Product: NPC95889

Natural Product IDNPC95889
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CUTSGEORQNCXRC-SQSUNLSESA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11781469
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000296] Benzodioxoles

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 CUTSGEORQNCXRC-SQSUNLSESA-N
Standard InCHI InChI=1S/C18H19NO3/c20-18(19-11-5-6-12-19)8-4-2-1-3-7-15-9-10-16-17(13-15)22-14-21-16/h1-4,7-10,13H,5-6,11-12,14H2/b2-1+,7-3+,8-4+
SMILES C(=CC=CC(=O)N1CCCC1)/C=C/c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   297.14 Volume:   313.127
?
Van der Waals volume.
Dense:   0.949 LogP:   2.284
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.503
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.511
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   38.77
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.633 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.539 Fsp3:   0.278
MCE-18:   34.087
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.657 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.692
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.803
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.036 Promiscuous compounds:   0.038

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.771 MDCK Permeability:   -4.684
Pgp-inhibitor:   0.878 Pgp-substrate:   0.017
PAMPA:   0.285
?
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):   0.002
20% Bioavailability (F20%):   0.109 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.751

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.118 MRP1:   0.01
Plasma Protein Binding (PPB):   95.496% Volume Distribution (VD):   -0.255
Fu: 4.797%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.95
OATP1B3 inhibitor:   0.914 BCRP inhibitor:   0.01
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.887 CYP1A2-substrate:   0.829
CYP2C19-inhibitor:   0.119 CYP2C19-substrate:   0.983
CYP2C9-inhibitor:   0.66 CYP2C9-substrate:   0.953
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.972
CYP3A4-inhibitor:   0.019 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.006 CYP2C8-inhibitor:   0.956
HLM stability:   0.743
?
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):  5.733 Half-life (T1/2):  0.649

ADMET: Toxicity

hERG Blockers:  0.337 hERG Blockers (10um):  0.447
Human Hepatotoxicity (H-HT):  0.642 Drug-induced Liver Injury (DILI):  0.707
AMES Toxicity:  0.828 Rat Oral Acute Toxicity:  0.413
Maximum Recommended Daily Dose:  0.745 Skin Sensitization:  0.652
Carcinogencity:  0.81 Eye Corrosion:  0.006
Eye Irritation:  0.636 Respiratory Toxicity:  0.827
Drug-induced Neurotoxicity:  0.734 Ototoxicity:  0.375
Hematotoxicity:  0.432 Drug-induced Nephrotoxicity:  0.532
Genotoxicity:  0.885 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.098 Hek293 Cytotoxicity:  0.507
BCF:   1.115
?
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:   3.668
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.31
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.675
?
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
NPO16915 Callyspongia aerizusa Species Callyspongiidae Eukaryota n.a. n.a. n.a. PMID[26213786]
NPO17517 Artemisia arborescens Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38592817]
NPO14795 Vitis coignetiae Species Vitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15369 Tabernaemontana rupicola Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2913 Tabebuia pentaphylla Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15893 Solandra guttata Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16447 Potato virus n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO16048 Euphorbia serrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15734 Euchresta horsfeldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21786 Culcitium serratifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17297 Caragana pygmaea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16915 Callyspongia aerizusa Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17517 Artemisia arborescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18069 Streptomyces coelicoflavus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO14795 Vitis coignetiae Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17517 Artemisia arborescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15893 Solandra guttata Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17297 Caragana pygmaea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15734 Euchresta horsfeldii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21786 Culcitium serratifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16048 Euphorbia serrata Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18069 Streptomyces coelicoflavus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO2913 Tabebuia pentaphylla Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16447 Potato virus n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO14795 Vitis coignetiae Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16915 Callyspongia aerizusa Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15369 Tabernaemontana rupicola Species Apocynaceae 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 NPC95889 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
0.9787 High Similarity NPC205178
0.9787 High Similarity NPC227218
0.9149 High Similarity NPC94280
0.8958 High Similarity NPC255817
0.8958 High Similarity NPC136330
0.7778 Intermediate Similarity NPC103947
0.7778 Intermediate Similarity NPC45783
0.7636 Intermediate Similarity NPC73883
0.7636 Intermediate Similarity NPC251454
0.7321 Intermediate Similarity NPC328419
0.7222 Intermediate Similarity NPC159150
0.72 Intermediate Similarity NPC217574
0.7193 Intermediate Similarity NPC220923
0.7193 Intermediate Similarity NPC196609
0.7059 Intermediate Similarity NPC167096
0.7059 Intermediate Similarity NPC605721
0.6786 Remote Similarity NPC193673
0.6667 Remote Similarity NPC230698
0.6667 Remote Similarity NPC99078
0.6667 Remote Similarity NPC96406
0.6296 Remote Similarity NPC470707
0.6034 Remote Similarity NPC145446
0.6034 Remote Similarity NPC137172
0.5763 Remote Similarity NPC194359
0.5763 Remote Similarity NPC28641
0.5763 Remote Similarity NPC180647
0.5763 Remote Similarity NPC225745
0.5741 Remote Similarity NPC199209
0.5574 Remote Similarity NPC318862
0.5556 Remote Similarity NPC95366
0.5424 Remote Similarity NPC252107
0.5345 Remote Similarity NPC469808
0.5306 Remote Similarity NPC127326
0.5246 Remote Similarity NPC248505
0.5238 Remote Similarity NPC251466
0.5098 Remote Similarity NPC111225

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC95889 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
0.8958 High Similarity NPD2492 Phase 2

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