Natural Product: NPC290928

Natural Product IDNPC290928
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QKBQWVMXPGSNTK-UJURSFKZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 118708002
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000050] Lactones
        • [CHEMONTID:0001245] Gamma butyrolactones

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 QKBQWVMXPGSNTK-UJURSFKZSA-N
Standard InCHI InChI=1S/C7H10O3/c1-4-6(5(2)8)3-10-7(4)9/h4,6H,3H2,1-2H3/t4-,6+/m0/s1
SMILES C[C@H]1[C@@H](COC1=O)C(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   142.06 Volume:   142.17
?
Van der Waals volume.
Dense:   0.999 LogP:   -0.396
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.097
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.184
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   7.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.497 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.675 Fsp3:   0.714
MCE-18:   17.5
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.294 Fluc inhibitor:   0.141
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.061
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.974 Promiscuous compounds:   0.798

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.614 MDCK Permeability:   -4.307
Pgp-inhibitor:   0.841 Pgp-substrate:   0.278
PAMPA:   0.524
?
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%):   0.105 30% Bioavailability (F30%):   0.134
50% Bioavailability (F50%):   0.427

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.029 MRP1:   0.842
Plasma Protein Binding (PPB):   20.336% Volume Distribution (VD):   -0.1
Fu: 76.982%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.957
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.138
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.233 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.115 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.008
CYP3A4-inhibitor:   0.378 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.011
HLM stability:   0.026
?
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):  2.915 Half-life (T1/2):  2.399

ADMET: Toxicity

hERG Blockers:  0.038 hERG Blockers (10um):  0.214
Human Hepatotoxicity (H-HT):  0.866 Drug-induced Liver Injury (DILI):  0.944
AMES Toxicity:  0.549 Rat Oral Acute Toxicity:  0.216
Maximum Recommended Daily Dose:  0.26 Skin Sensitization:  0.991
Carcinogencity:  0.65 Eye Corrosion:  0.725
Eye Irritation:  0.975 Respiratory Toxicity:  0.356
Drug-induced Neurotoxicity:  0.687 Ototoxicity:  0.462
Hematotoxicity:  0.531 Drug-induced Nephrotoxicity:  0.899
Genotoxicity:  0.953 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.063 Hek293 Cytotoxicity:  0.099
BCF:   0.259
?
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:   2.435
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.71
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.281
?
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
NPO18268 Mycoleptodonoides aitchisonii Species n.a. Eukaryota n.a. n.a. n.a. DOI[10.1016/j.tet.2008.10.068]
NPO7811 Scleronephthya pallida Species Nephtheidae Eukaryota n.a. n.a. n.a. PMID[10075773]
NPO10376 Arcyria denudata Species Trichiidae Eukaryota n.a. n.a. n.a. PMID[16933891]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[18464091]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[18558747]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota stem bark Pangradin village, Jasinga, West Java, Indonesia 2005-AUG PMID[19839614]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[20817450]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. pericarp n.a. PMID[24555285]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. PMID[24717154]
NPO18268 Mycoleptodonoides aitchisonii Species n.a. Eukaryota n.a. n.a. n.a. PMID[24988471]
NPO18268 Mycoleptodonoides aitchisonii Species n.a. Eukaryota Mature fruiting bodies Narusawa Village, Yamanashi Prefecture, in Japan 2006-AUG PMID[24988471]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota fruit hulls Madras, Tamil Nadu, India 1993-MAR PMID[9213587]
NPO8560 Aplidium tabascum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3707 Chromatium okenii Species Chromatiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO9741 Actinopyga agassizi Species Holothuriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18268 Mycoleptodonoides aitchisonii Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10376 Arcyria denudata Species Trichiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8354 Aster bellidiastrum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4064 Halimodendron halodendron Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7534 Leptogorgia sarmentosa Species Gorgoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3449 Lonicera hypoleuca Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24931 Myelochroa aurulenta Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10056 Nicotiana sylvestris Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8927 Poria selecta Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7811 Scleronephthya pallida Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25216 Senecio vellereus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27924 Serpocaulon triseriale Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10221 Streptomyces alboniger Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12600 Trametes cinnabarina Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9717 Wibelia divaricata Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO10849 Eucalyptus camaldulensis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10849 Eucalyptus camaldulensis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9741 Actinopyga agassizi Species Holothuriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3707 Chromatium okenii Species Chromatiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6249 Garcinia mangostana Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27924 Serpocaulon triseriale Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10391 Dolomiaea souliei Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4064 Halimodendron halodendron Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10376 Arcyria denudata Species Trichiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8354 Aster bellidiastrum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12600 Trametes cinnabarina Species Coriolaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8560 Aplidium tabascum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3449 Lonicera hypoleuca Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10221 Streptomyces alboniger Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO10056 Nicotiana sylvestris Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7534 Leptogorgia sarmentosa Species Gorgoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24931 Myelochroa aurulenta Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10849 Eucalyptus camaldulensis Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8927 Poria selecta Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7811 Scleronephthya pallida Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25216 Senecio vellereus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9717 Wibelia divaricata Species Davalliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18268 Mycoleptodonoides aitchisonii Species n.a. 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 NPC290928 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 NPC290928 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