Natural Product: NPC200085

Natural Product IDNPC200085
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Naramycin B
IUPAC Name 4-[(2R)-2-[(1R,3S,5S)-3,5-dimethyl-2-oxocyclohexyl]-2-hydroxyethyl]piperidine-2,6-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1078564
PubChem CID 120760
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000089] Pyridines and derivatives
        • [CHEMONTID:0002224] Hydropyridines
          • [CHEMONTID:0001934] Tetrahydropyridines

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-GAIPPQHRSA-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:   0.713
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.892
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.805
?
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:   0.255 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
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:   0.575

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.807 MDCK Permeability:   -4.555
Pgp-inhibitor:   0.069 Pgp-substrate:   0.069
PAMPA:   0.826
?
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%):   0.021

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.064 MRP1:   0.909
Plasma Protein Binding (PPB):   48.404% Volume Distribution (VD):   0.007
Fu: 50.496%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.003
BSEP inhibitor:   0.84

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.025 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.133 CYP3A4-substrate:   0.025
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.113
HLM stability:   0.07
?
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):  6.043 Half-life (T1/2):  1.413

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.033
Human Hepatotoxicity (H-HT):  0.996 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  0.532 Rat Oral Acute Toxicity:  0.693
Maximum Recommended Daily Dose:  0.92 Skin Sensitization:  0.998
Carcinogencity:  0.925 Eye Corrosion:  0.0
Eye Irritation:  0.034 Respiratory Toxicity:  0.876
Drug-induced Neurotoxicity:  0.707 Ototoxicity:  0.869
Hematotoxicity:  0.866 Drug-induced Nephrotoxicity:  0.999
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.018
A549 Cytotoxicity:  0.006 Hek293 Cytotoxicity:  0.155
BCF:   0.21
?
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:   2.848
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.113
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.32
?
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]
NPO40218 Streptomyces sp. H7667 Strain Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[19711989]
NPO12485 Ceiba pentandra Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[8133294]
NPO12485 Ceiba pentandra Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[9461647]
NPO729 Espeletia marcana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9020 Eriostemon fitzgeraldii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2805 Distolasterias nipon Species Asteriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5219 Dendrobium rotundatum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18350 Culcitium canescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9603 Croton sparsiflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12481 Croton californicus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7365 Clibadium pentaneuron Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1937 Andropogon nardus Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7883 Albugo candida Species Albuginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3333 Aglaia gigantea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12378 Streptomyces blastmyceticus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO1526 Ratibida latipalearis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40218 Streptomyces sp. H7667 Strain Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12485 Ceiba pentandra Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9227 Xylaria berteri Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9320 Weddellina squamulosa Species Podostemaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12535 Solanum toxicarium Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24849 Rhinella paracnemis Species Bufonidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10867 Graphis elongata Species Aclididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9937 Piptolepis leptospermoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8416 Picrorhiza kurrooa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3900 Phellinus xeranticus Species Hymenochaetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8547 Petasites niveus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3202 Nolina erumpens Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6787 Neoalsomitra integrifolia Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12309 Malva crispa Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11355 Homarus americanus Species Nephropidae 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]
NPO12485 Ceiba pentandra Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9603 Croton sparsiflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8416 Picrorhiza kurrooa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9603 Croton sparsiflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24652 Toxicodendron succedaneum Species Anacardiaceae 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]
NPO9020 Eriostemon fitzgeraldii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8547 Petasites niveus 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]
NPO10867 Graphis elongata Species Aclididae 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]
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]
NPO12378 Streptomyces blastmyceticus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO1526 Ratibida latipalearis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2821 Polysphondylium violaceum Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12485 Ceiba pentandra Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8995 Angelica capitellata 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

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
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT150 Individual protein Anthrax lethal factor Bacillus anthracis Potency = 199.5 nM PubChem BioAssay data set
NPT150 Individual protein Anthrax lethal factor Bacillus anthracis Potency = 125.9 nM PubChem BioAssay data set
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens AC50 = 15848.93 nM PubChem BioAssay data set
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens AC50 = 39810.72 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 28183.8 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 100.0 nM PubChem BioAssay data set
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IZ = 12.0 mm PMID[19711989]
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IZ = 15.0 mm PMID[19711989]
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IZ = 16.0 mm PMID[19711989]
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IZ = 22.0 mm PMID[19711989]
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IZ = 25.0 mm PMID[19711989]
NPT591 Individual protein Glycogen synthase kinase-3 beta Homo sapiens IZ = 33.0 mm PMID[19711989]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency = 3162.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency = 446.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 3162.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 1258.9 nM PubChem BioAssay data set

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 NPC200085 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 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 NPC200085 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