Natural Product: NPC136091

Natural Product IDNPC136091
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KCWZGJVSDFYRIX-YFKPBYRVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 39836
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0000060] Alpha amino acids and derivatives
              • [CHEMONTID:0004320] Arginine and derivatives

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 KCWZGJVSDFYRIX-YFKPBYRVSA-N
Standard InCHI InChI=1S/C7H15N5O4/c1-16-6(13)5(8)3-2-4-10-7(9)11-12(14)15/h5H,2-4,8H2,1H3,(H3,9,10,11)/t5-/m0/s1
SMILES COC(=O)[C@H](CCCNC(=N)NN(=O)=O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   233.11 Volume:   211.864
?
Van der Waals volume.
Dense:   1.1 LogP:   -1.609
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.976
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.09
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   3.0
TPSA:   143.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   0.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.11 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.43 Fsp3:   0.714
MCE-18:   4.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.229 Fluc inhibitor:   0.043
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.013
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.015 Promiscuous compounds:   0.1

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.836 MDCK Permeability:   -4.921
Pgp-inhibitor:   0.0 Pgp-substrate:   0.851
PAMPA:   0.997
?
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):   0.002
20% Bioavailability (F20%):   0.011 30% Bioavailability (F30%):   0.077
50% Bioavailability (F50%):   0.026

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.82
Plasma Protein Binding (PPB):   19.659% Volume Distribution (VD):   -0.132
Fu: 77.757%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.759
OATP1B3 inhibitor:   0.864 BCRP inhibitor:   0.0
BSEP inhibitor:   0.026

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.069 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.986 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.284 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.006
?
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):  6.133 Half-life (T1/2):  0.766

ADMET: Toxicity

hERG Blockers:  0.094 hERG Blockers (10um):  0.504
Human Hepatotoxicity (H-HT):  0.437 Drug-induced Liver Injury (DILI):  0.723
AMES Toxicity:  0.87 Rat Oral Acute Toxicity:  0.697
Maximum Recommended Daily Dose:  0.046 Skin Sensitization:  1.0
Carcinogencity:  0.519 Eye Corrosion:  0.003
Eye Irritation:  0.639 Respiratory Toxicity:  0.972
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.14
Hematotoxicity:  0.084 Drug-induced Nephrotoxicity:  0.665
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.022
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.707
BCF:   0.218
?
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:   2.902
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.319
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.44
?
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
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[22281186]
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[27588326]
NPO40498 Montagnulaceae sp. DM0194 Strain Didymosphaeriaceae Eukaryota n.a. n.a. n.a. PMID[28099011]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[32319765]
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18007 Agrimonia pilosa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8500 Acanthopanax gracilistylus Species Araliaceae 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
NPT270 Individual protein Nitric oxide synthase, inducible Mus musculus IC50 = 2600.0 nM PMID[7518001]
NPT3517 Individual protein Nitric oxide synthase, inducible Homo sapiens IC50 = 14000.0 nM PMID[11327580]
NPT269 Individual protein Nitric-oxide synthase, brain Rattus norvegicus IC50 = 150.0 nM PMID[11327580]
NPT3517 Individual protein Nitric oxide synthase, inducible Homo sapiens IC50 = 300000000.0 nM PMID[11327580]
NPT3517 Individual protein Nitric oxide synthase, inducible Homo sapiens IC50 = 8000.0 nM PMID[12781178]
NPT3517 Individual protein Nitric oxide synthase, inducible Homo sapiens IC50 = 14000.0 nM PMID[12620067]
NPT3517 Individual protein Nitric oxide synthase, inducible Homo sapiens IC50 = 8000.0 nM PMID[12182860]
NPT270 Individual protein Nitric oxide synthase, inducible Mus musculus IC50 = 25800.0 nM PMID[18926710]
NPT270 Individual protein Nitric oxide synthase, inducible Mus musculus IC50 = 25800.0 nM PMID[21115251]
NPT270 Individual protein Nitric oxide synthase, inducible Mus musculus IC50 = 13350.0 nM PMID[22115618]
NPT270 Individual protein Nitric oxide synthase, inducible Mus musculus Inhibition > 70.0 % PMID[22560043]
NPT1778 Individual protein Serotonin 2a (5-HT2a) receptor Rattus norvegicus Activity n.a. n.a. n.a. PMID[36075145]
NPT3517 Individual protein Nitric oxide synthase, inducible Homo sapiens Ki = 70000.0 nM PMID[36063653]
NPT3517 Individual protein Nitric oxide synthase, inducible Homo sapiens IC50 = 13500.0 nM PMID[36641860]
NPT269 Individual protein Nitric-oxide synthase, brain Rattus norvegicus IC50 = 70000.0 nM PMID[36063653]
NPT4415 Individual protein Nitric-oxide synthase, endothelial Bos taurus IC50 = 100000.0 nM PMID[7518001]
NPT29579 Single protein Urokinase plasminogen activator surface receptor Homo sapiens RU = 0.0 n.a. PMID[36854648]
NPT30000 Single protein Nitric oxide synthase, endothelial Rattus norvegicus Inhibition n.a. n.a. % PMID[34218000]
NPT3569 Individual protein Nitric-oxide synthase, brain Homo sapiens IC50 = 1600.0 nM PMID[12781178]
NPT3569 Individual protein Nitric-oxide synthase, brain Homo sapiens IC50 = 150.0 nM PMID[12620067]
NPT3569 Individual protein Nitric-oxide synthase, brain Homo sapiens IC50 = 1600.0 nM PMID[12182860]
NPT3974 Individual protein Nitric-oxide synthase, endothelial Homo sapiens IC50 = 2700.0 nM PMID[11327580]
NPT3974 Individual protein Nitric-oxide synthase, endothelial Homo sapiens IC50 = 1500.0 nM PMID[12781178]
NPT3974 Individual protein Nitric-oxide synthase, endothelial Homo sapiens IC50 = 2700.0 nM PMID[12620067]
NPT3974 Individual protein Nitric-oxide synthase, endothelial Homo sapiens IC50 = 1500.0 nM PMID[12182860]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT579 Cell line DLD-1 Homo sapiens IC50 > 300000.0 nM PMID[12620067]
NPT1182 Cell line J774.A1 Mus musculus Inhibition = 69.49 % PMID[15664809]
NPT1182 Cell line J774.A1 Mus musculus Inhibition = 20.37 % PMID[15664809]
NPT1182 Cell line J774.A1 Mus musculus Inhibition = 12.8 % PMID[15664809]
NPT34 Cell line BV-2 Mus musculus IC50 = 36000.0 nM PMID[17046255]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 198300.0 nM PMID[11000020]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 116200.0 nM PMID[11000020]
NPT848 Cell line N9 Homo sapiens Inhibition = 44.2 % PMID[11087610]
NPT848 Cell line N9 Homo sapiens Inhibition = 32.2 % PMID[11087610]
NPT848 Cell line N9 Homo sapiens Inhibition = 15.7 % PMID[11087610]
NPT848 Cell line N9 Homo sapiens IC50 = 630000.0 nM PMID[11087610]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 27130.0 nM PMID[19359068]
NPT1182 Cell line J774.A1 Mus musculus Inhibition = 46.56 % PMID[19634889]
NPT34 Cell line BV-2 Mus musculus IC50 = 25800.0 nM PMID[21028898]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 48500.0 nM PMID[21435874]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 26210.0 nM DOI[10.1007/s00044-010-9521-0]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 23210.0 nM DOI[10.1007/s00044-011-9706-1]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 170040.0 nM PMID[23566521]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 69210.0 nM PMID[25113933]
NPT1182 Cell line J774.A1 Mus musculus IC50 = 73180.0 nM PMID[25113933]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 69210.0 nM PMID[24909081]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 53600.0 nM PMID[25412141]
NPT1182 Cell line J774.A1 Mus musculus IC50 = 73180.0 nM PMID[25824662]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 69210.0 nM PMID[25824662]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 53.0 % PMID[27040659]
NPT34 Cell line BV-2 Mus musculus IC50 = 24700.0 nM PMID[27588326]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 30600.0 nM PMID[28099011]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 58400.0 nM PMID[32319765]
NPT34 Cell line BV-2 Mus musculus Inhibition = 70.5 % PMID[33422907]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM DOI[10.6019/CHEMBL4651402]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM DOI[10.6019/CHEMBL4651402]
NPT22974 Selectivity group Nitric oxide sythases; iNOS & nNOS Homo sapiens Ratio = 5.0 n.a. PMID[12182860]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 6.6 % PMID[11087610]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 15.6 % PMID[11087610]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 16.8 % PMID[11087610]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 510000.0 nM PMID[11087610]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 73180.0 nM PMID[24909081]
NPT16957 Selectivity group Nitric-oxide synthase (endothelial and brain) Homo sapiens Ratio = 1.0 n.a. PMID[12182860]
NPT2 Others Unspecified n.a. IC50 = 20100.0 nM PMID[18161942]
NPT2 Others Unspecified n.a. IC50 = 18900.0 nM PMID[21377368]

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 = 42.7 mm PMID[26009162]
NPT32 Organism Mus musculus Mus musculus Activity = 35.7 mm PMID[27810240]
NPT29 Organism Rattus norvegicus Rattus norvegicus ID50 > 300.0 umol.kg-1 PMID[12620067]





 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
- Rattus norvegicus NOEL = 80.0 mg/L 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 NPC136091 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
0.9744 High Similarity NPC601306
0.5435 Remote Similarity NPC601871
0.5306 Remote Similarity NPC331434
0.5098 Remote Similarity NPC609170

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC136091 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
1.0 High Similarity NPD9224 Phase 2

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