Natural Product: NPC28737

Natural Product IDNPC28737
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YPHMISFOHDHNIV-BSJXLVFVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 7059507
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000195] Piperidines
        • [CHEMONTID:0001581] Piperidinones
          • [CHEMONTID:0001582] Piperidinediones

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 YPHMISFOHDHNIV-BSJXLVFVSA-N
Standard InCHI InChI=1S/C15H23NO4/c1-8-3-9(2)15(20)11(4-8)12(17)5-10-6-13(18)16-14(19)7-10/h8-12,17H,3-7H2,1-2H3,(H,16,18,19)/t8-,9+,11-,12+/m0/s1
SMILES C[C@H]1C[C@@H](C)C(=O)[C@@H](C1)[C@@H](CC1CC(=NC(=O)C1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   281.16 Volume:   289.132
?
Van der Waals volume.
Dense:   0.972 LogP:   1.028
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.362
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.08
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   86.96
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.827 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.713 Fsp3:   0.8
MCE-18:   36.296
?
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:   0.245 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.012
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.023
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.179 Promiscuous compounds:   0.581

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.851 MDCK Permeability:   -4.613
Pgp-inhibitor:   0.061 Pgp-substrate:   0.004
PAMPA:   0.532
?
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%):   0.001 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.039

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.978
Plasma Protein Binding (PPB):   46.491% Volume Distribution (VD):   0.154
Fu: 47.896%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.974
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.0
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.852 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.652 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.643 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.013
CYP3A4-inhibitor:   0.045 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.166
HLM stability:   0.186
?
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):  6.165 Half-life (T1/2):  1.288

ADMET: Toxicity

hERG Blockers:  0.009 hERG Blockers (10um):  0.031
Human Hepatotoxicity (H-HT):  0.994 Drug-induced Liver Injury (DILI):  0.999
AMES Toxicity:  0.698 Rat Oral Acute Toxicity:  0.49
Maximum Recommended Daily Dose:  0.792 Skin Sensitization:  0.998
Carcinogencity:  0.928 Eye Corrosion:  0.0
Eye Irritation:  0.156 Respiratory Toxicity:  0.848
Drug-induced Neurotoxicity:  0.589 Ototoxicity:  0.885
Hematotoxicity:  0.855 Drug-induced Nephrotoxicity:  0.998
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.007 Hek293 Cytotoxicity:  0.19
BCF:   0.198
?
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:   2.843
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.074
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.303
?
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
NPO3333 Aglaia gigantea Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[17880174]
NPO1526 Ratibida latipalearis Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[1800631]
NPO10867 Graphis elongata Species Aclididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3333 Aglaia gigantea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7883 Albugo candida Species Albuginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1937 Andropogon nardus Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7365 Clibadium pentaneuron Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12481 Croton californicus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9603 Croton sparsiflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18350 Culcitium canescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5219 Dendrobium rotundatum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2805 Distolasterias nipon Species Asteriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9020 Eriostemon fitzgeraldii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO729 Espeletia marcana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11355 Homarus americanus Species Nephropidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12309 Malva crispa Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6787 Neoalsomitra integrifolia Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3202 Nolina erumpens Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8547 Petasites niveus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3900 Phellinus xeranticus Species Hymenochaetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8416 Picrorhiza kurrooa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9937 Piptolepis leptospermoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1526 Ratibida latipalearis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24849 Rhinella paracnemis Species Bufonidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12535 Solanum toxicarium Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9320 Weddellina squamulosa Species Podostemaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9227 Xylaria berteri Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8416 Picrorhiza kurrooa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9603 Croton sparsiflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8416 Picrorhiza kurrooa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9603 Croton sparsiflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8416 Picrorhiza kurrooa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10867 Graphis elongata Species Aclididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8547 Petasites niveus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9603 Croton sparsiflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8416 Picrorhiza kurrooa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6787 Neoalsomitra integrifolia Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5219 Dendrobium rotundatum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO729 Espeletia marcana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2805 Distolasterias nipon Species Asteriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24849 Rhinella paracnemis Species Bufonidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7883 Albugo candida Species Albuginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3900 Phellinus xeranticus Species Hymenochaetaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7365 Clibadium pentaneuron Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11355 Homarus americanus Species Nephropidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9020 Eriostemon fitzgeraldii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12481 Croton californicus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12309 Malva crispa Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12535 Solanum toxicarium Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3202 Nolina erumpens Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9227 Xylaria berteri Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1937 Andropogon nardus Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3333 Aglaia gigantea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9320 Weddellina squamulosa Species Podostemaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18350 Culcitium canescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9937 Piptolepis leptospermoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1526 Ratibida latipalearis Species Asteraceae 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 NPC28737 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 NPC200085
1.0 High Similarity NPC253703
1.0 High Similarity NPC51695
0.6957 Remote Similarity NPC198855
0.6809 Remote Similarity NPC279122
0.6667 Remote Similarity NPC487836

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC28737 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