Natural Product: NPC602821

Natural Product IDNPC602821
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YCWQAMGASJSUIP-YFKPBYRVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL97485
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 YCWQAMGASJSUIP-YFKPBYRVSA-N
Standard InCHI InChI=1S/C6H9N3O3/c7-5(6(11)12)2-1-4(10)3-9-8/h3,5H,1-2,7H2,(H,11,12)/t5-/m0/s1
SMILES [N-]=[N+]=CC(=O)CC[C@H](N)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   171.06 Volume:   161.147
?
Van der Waals volume.
Dense:   1.062 LogP:   -2.207
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.538
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.75
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   4.0
TPSA:   116.79
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   0.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.315 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.82 Fsp3:   0.5
MCE-18:   3.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.375 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.035
?
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:   0.235 Promiscuous compounds:   0.246

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.753 MDCK Permeability:   -4.606
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   1.0
?
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%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.004
Plasma Protein Binding (PPB):   14.719% Volume Distribution (VD):   -0.636
Fu: 91.072%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.266 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.0
?
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):  5.159 Half-life (T1/2):  1.06

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.99
Human Hepatotoxicity (H-HT):  0.963 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  1.0 Rat Oral Acute Toxicity:  0.995
Maximum Recommended Daily Dose:  0.986 Skin Sensitization:  1.0
Carcinogencity:  1.0 Eye Corrosion:  0.612
Eye Irritation:  1.0 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  1.0 Ototoxicity:  0.022
Hematotoxicity:  0.986 Drug-induced Nephrotoxicity:  1.0
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.024
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.504
BCF:   0.301
?
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:   2.972
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.996
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.338
?
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
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[11141106]
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[11374972]
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[15217282]
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[15270566]
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]

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 AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT100 Individual protein Glutaminase kidney isoform, mitochondrial Homo sapiens Inhibition = 84.1 % PMID[37011768]
NPT893 Individual protein Monoamine oxidase B Mus musculus Activity n.a. n.a. n.a. PMID[18834112]
NPT21123 Single protein Amino acid transporter Rattus norvegicus Inhibition >= 25.0 % US-8741955-B2
NPT29547 Single protein Glutaminase kidney isoform, mitochondrial Mus musculus Inhibition = 65.5 % PMID[37011768]
NPT29547 Single protein Glutaminase kidney isoform, mitochondrial Mus musculus Inhibition n.a. n.a. % PMID[37011768]
NPT892 Individual protein Monoamine oxidase A Mus musculus Activity n.a. n.a. n.a. PMID[18834112]
NPT29547 Single protein Glutaminase kidney isoform, mitochondrial Mus musculus Inhibition = 55.5 % PMID[37011768]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. K+2/Ki = 0.07 uM min-1 PMID[11133094]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT28438 Unchecked Unchecked n.a. Ratio = 0.006 n.a. PMID[28759224]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[30892035]
NPT28438 Unchecked Unchecked n.a. EC50 = 10000.0 nM PMID[30892035]
NPT1114 Organism Human immunodeficiency virus Human immunodeficiency virus Activity n.a. n.a. n.a. PMID[28759224]
NPT28438 Unchecked Unchecked n.a. Ratio = 0.543 n.a. PMID[28759224]
NPT28438 Unchecked Unchecked n.a. K+2 = 0.7 min-1 PMID[11133094]
NPT28438 Unchecked Unchecked n.a. Ki = 9500.0 nM PMID[11133094]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 100.0 % PMID[18456372]
NPT20 Organism Candida albicans Candida albicans MIC = 4.0 ug.mL-1 PMID[18794383]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 0.5 ug.mL-1 PMID[18794383]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 0.125 ug.mL-1 PMID[18794383]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 100.0 % PMID[20133022]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 251.0 mm3 PMID[27560860]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 256.0 mm3 PMID[27560860]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 364.0 mm3 PMID[27560860]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 504.0 mm3 PMID[27560860]
NPT20 Organism Candida albicans Candida albicans MIC = 1.0 ug.mL-1 PMID[18794383]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 0.25 ug.mL-1 PMID[18794383]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition > 50.0 % PMID[27560860]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity n.a. n.a. n.a. PMID[28759224]
NPT32 Organism Mus musculus Mus musculus Activity n.a. n.a. n.a. PMID[27560860]
NPT32 Organism Mus musculus Mus musculus Inhibition n.a. n.a. % PMID[27560860]
NPT32 Organism Mus musculus Mus musculus Activity = 12.0 % PMID[27560860]





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference
Saccharomyces cerevisiae n.a. Drug uptake = 2.25 nmol/min PMID[18794383]
Saccharomyces cerevisiae n.a. Drug uptake = 32.0 % PMID[18794383]
Saccharomyces cerevisiae n.a. Drug uptake = 1.98 nmol/min PMID[18794383]
Saccharomyces cerevisiae n.a. Drug uptake = 2.32 nmol/min PMID[18794383]
Saccharomyces cerevisiae n.a. Drug uptake = 2.0 nmol/min PMID[18794383]
Macaca nemestrina Plasma AUC = 7308.53 ng.hr.mL-1 PMID[27560860]
Sus scrofa Brain/Plasma BPR = 0.148 n.a. PMID[28759224]
Macaca nemestrina Cerebrospinal fluid Drug uptake = 0.33 nmol/g PMID[27560860]
Macaca nemestrina Plasma Cmax = 12600.0 nM PMID[27560860]
Mus musculus Plasma AUC = 213.95 ng.hr.mL-1 PMID[27560860]
Mus musculus Plasma Cmax = 2200.0 nM PMID[27560860]
Mus musculus Brain Cmax = 0.56 nmol/g PMID[27560860]
Mus musculus Plasma Tmax = 0.17 hr PMID[27560860]
Macaca nemestrina Plasma Tmax = 0.25 hr PMID[27560860]
Sus scrofa Brain Drug uptake = 5.15 nmol/g PMID[28759224]
Mus musculus Brain Tmax = 0.5 hr PMID[27560860]
Mus musculus Brain/Plasma BPR = 0.46 n.a. PMID[27560860]
Mus musculus Brain AUCt = 0.57 nmol.hr/g PMID[27560860]
Sus scrofa Brain Drug uptake(free) = 0.46 nmol/g PMID[28759224]
Sus scrofa Cerebrospinal fluid Drug uptake = 0.252 nmol/ml PMID[28759224]
Sus scrofa Brain Drug uptake(free) = 0.464 nmol/g PMID[28759224]





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference
- Mus musculus LD50 = 197.0 mg/kg ToxVal

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 NPC602821 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 NPC602821 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