Natural Product: NPC96128

Natural Product IDNPC96128
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VJQAFLAZRVKAKM-VZLIPTOUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 442266
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 VJQAFLAZRVKAKM-VZLIPTOUSA-N
Standard InCHI InChI=1S/C15H16O5/c1-6-3-9(17)12-7(2)15(19)20-14(12)13-8(5-16)4-10(18)11(6)13/h4,9,12-14,16-17H,2-3,5H2,1H3/t9-,12+,13-,14-/m0/s1
SMILES CC1=C2C(=O)C=C(CO)[C@@H]2[C@@H]2[C@H](C(=C)C(=O)O2)[C@H](C1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   276.1 Volume:   273.096
?
Van der Waals volume.
Dense:   1.011 LogP:   0.725
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.126
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.64
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.531 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.614 Fsp3:   0.467
MCE-18:   46.636
?
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:   0.261 Fluc inhibitor:   0.062
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.4
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.064
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.359 Promiscuous compounds:   0.532

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.863 MDCK Permeability:   -4.765
Pgp-inhibitor:   0.018 Pgp-substrate:   0.775
PAMPA:   0.943
?
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):   0.272
20% Bioavailability (F20%):   0.217 30% Bioavailability (F30%):   0.83
50% Bioavailability (F50%):   0.77

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.062 MRP1:   0.477
Plasma Protein Binding (PPB):   58.282% Volume Distribution (VD):   -0.059
Fu: 43.516%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.739
OATP1B3 inhibitor:   0.941 BCRP inhibitor:   0.024
BSEP inhibitor:   0.663

ADMET: Metabolism

CYP1A2-inhibitor:   0.031 CYP1A2-substrate:   0.105
CYP2C19-inhibitor:   0.049 CYP2C19-substrate:   0.011
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.059
CYP3A4-inhibitor:   0.147 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.965
HLM stability:   0.457
?
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):  5.585 Half-life (T1/2):  2.185

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.163
Human Hepatotoxicity (H-HT):  0.766 Drug-induced Liver Injury (DILI):  0.908
AMES Toxicity:  0.923 Rat Oral Acute Toxicity:  0.342
Maximum Recommended Daily Dose:  0.329 Skin Sensitization:  0.998
Carcinogencity:  0.815 Eye Corrosion:  0.016
Eye Irritation:  0.787 Respiratory Toxicity:  0.323
Drug-induced Neurotoxicity:  0.415 Ototoxicity:  0.554
Hematotoxicity:  0.923 Drug-induced Nephrotoxicity:  0.925
Genotoxicity:  0.934 RPMI-8226 Immunitoxicity:  0.297
A549 Cytotoxicity:  0.298 Hek293 Cytotoxicity:  0.279
BCF:   0.544
?
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:   3.195
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.932
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.244
?
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
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11627-001-0052-8]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[18341288]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[18460139]
NPO53708 Struchium sparganophora Genus Asteraceae Eukaryota n.a. n.a. n.a. PMID[35315297]
NPO22235 Azorella madreporica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[9677287]
NPO20175 Aegopodium podagraria Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12407 Herba cichorii n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29531 Lupinus cosentinii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO513 Agathosma scaberula Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13123 Balanophora harlandii Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO245 Euphorbia biglandulosa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17549 Polemonium caeruleum Species Polemoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2161 Strychnos ledermannii Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4892 Viburnum davidii Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22989 Penicillium daleae Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22235 Azorella madreporica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO698 Podocarpus totara Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11723 Pleurotus eryngii Species Pleurotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4151 Rhamnus wightii Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2434 Lipotriche scandens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8002 Solanum olgae Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8975 Aconitum nemorum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4787 Capuronianthus mahafalensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10756 Callitris drummondii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16931 Cichorium glandulosum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1584 Tolypothrix tjipanasensis Species Tolypothrichaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota Roots n.a. Database[FooDB]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8975 Aconitum nemorum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11723 Pleurotus eryngii Species Pleurotaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23053 Strychnos nitida Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO11723 Pleurotus eryngii Species Pleurotaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25693 Populus x canadensis Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23053 Strychnos nitida Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8975 Aconitum nemorum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15979 Erigeron multiradiatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12407 Herba cichorii n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8975 Aconitum nemorum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23053 Strychnos nitida Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16931 Cichorium glandulosum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4892 Viburnum davidii Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17549 Polemonium caeruleum Species Polemoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8002 Solanum olgae Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO698 Podocarpus totara Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1584 Tolypothrix tjipanasensis Species Tolypothrichaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO18513 Saccobasis polita Species Scapaniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13123 Balanophora harlandii Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2434 Lipotriche scandens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1854 Cardiospermum hirsutum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29531 Lupinus cosentinii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22989 Penicillium daleae Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9865 Cichorium intybus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO245 Euphorbia biglandulosa Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4151 Rhamnus wightii Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2161 Strychnos ledermannii Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16931 Cichorium glandulosum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2776 Lactuca sativa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23053 Strychnos nitida Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21624 Chondrophycus papillosus Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11723 Pleurotus eryngii Species Pleurotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25693 Populus x canadensis Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8975 Aconitum nemorum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4787 Capuronianthus mahafalensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15979 Erigeron multiradiatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20175 Aegopodium podagraria Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22628 Centaurea derventana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO513 Agathosma scaberula Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20035 Empleurum unicapsulare Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10756 Callitris drummondii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22235 Azorella madreporica Species Apiaceae 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
NPO53708 Struchium sparganophora n.a. n.a. 57.54 n.a. n.a. μg/100g PMID[35315297]
NPO9865 Cichorium intybus n.a. n.a. 178 to 245 n.a. n.a. mg/kg of FW PMID[18460139]

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 NPC96128 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
1.0 High Similarity NPC129419
0.7826 Intermediate Similarity NPC287387
0.68 Remote Similarity NPC268298
0.5273 Remote Similarity NPC237540

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC96128 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