Natural Product: NPC604272

Natural Product IDNPC604272
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DGYHPLMPMRKMPD-SCSAIBSYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL51369
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 DGYHPLMPMRKMPD-SCSAIBSYSA-N
Standard InCHI InChI=1S/C5H7NO2/c1-2-3-4(6)5(7)8/h1,4H,3,6H2,(H,7,8)/t4-/m1/s1
SMILES C#CC[C@@H](N)C(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   113.05 Volume:   115.704
?
Van der Waals volume.
Dense:   0.977 LogP:   -1.942
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.331
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.207
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   2.0
TPSA:   63.32
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   0.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.471 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.526 Fsp3:   0.4
MCE-18:   2.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.745 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.833 Promiscuous compounds:   0.315

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.424 MDCK Permeability:   -4.34
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.999
?
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%):   0.007 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.82

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.193 MRP1:   0.001
Plasma Protein Binding (PPB):   24.595% Volume Distribution (VD):   -0.171
Fu: 79.482%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.914
OATP1B3 inhibitor:   0.932 BCRP inhibitor:   0.001
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.009 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.094 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.764 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.009
HLM stability:   0.026
?
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):  9.181 Half-life (T1/2):  2.235

ADMET: Toxicity

hERG Blockers:  0.015 hERG Blockers (10um):  0.099
Human Hepatotoxicity (H-HT):  0.3 Drug-induced Liver Injury (DILI):  0.014
AMES Toxicity:  0.556 Rat Oral Acute Toxicity:  0.331
Maximum Recommended Daily Dose:  0.054 Skin Sensitization:  0.826
Carcinogencity:  0.38 Eye Corrosion:  0.317
Eye Irritation:  0.813 Respiratory Toxicity:  0.684
Drug-induced Neurotoxicity:  0.539 Ototoxicity:  0.275
Hematotoxicity:  0.076 Drug-induced Nephrotoxicity:  0.853
Genotoxicity:  0.09 RPMI-8226 Immunitoxicity:  0.111
A549 Cytotoxicity:  0.005 Hek293 Cytotoxicity:  0.03
BCF:   0.356
?
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:   2.517
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.537
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.116
?
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
NPO52746 Streptomyces sp. # 8-4 (HLR-599A) Genus 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT172 Organism Proteus mirabilis Proteus mirabilis MIC > 100.0 ug.mL-1 PMID[6417332]
NPT1122 Organism Haemophilus influenzae Haemophilus influenzae MIC > 100.0 ug.mL-1 PMID[6417332]
NPT2909 Organism Shigella flexneri Shigella flexneri MIC > 100.0 ug.mL-1 PMID[6417332]
NPT1033 Organism Enterobacter cloacae Enterobacter cloacae MIC > 100.0 ug.mL-1 PMID[6417332]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC > 100.0 ug.mL-1 PMID[6417332]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC > 100.0 ug.mL-1 PMID[6417332]
NPT2710 Organism Streptococcus agalactiae Streptococcus agalactiae MIC > 100.0 ug.mL-1 PMID[6417332]
NPT1228 Organism Streptococcus pyogenes Streptococcus pyogenes MIC > 100.0 ug.mL-1 PMID[6417332]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 50.0 ug.mL-1 PMID[6417332]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC > 100.0 ug.mL-1 PMID[6417332]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 100.0 ug.mL-1 PMID[6417332]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[6417332]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC > 100.0 ug.mL-1 PMID[6417332]
NPT3495 Organism Morganella morganii Morganella morganii MIC > 100.0 ug.mL-1 PMID[6417332]
NPT1248 Organism Serratia marcescens Serratia marcescens MIC > 100.0 ug.mL-1 PMID[6417332]
NPT29356 Organism Klebsiella aerogenes Klebsiella aerogenes MIC > 100.0 ug.mL-1 PMID[6417332]

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 NPC604272 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 NPC607953
0.6842 Remote Similarity NPC63621
0.6842 Remote Similarity NPC326992
0.6842 Remote Similarity NPC121517
0.6842 Remote Similarity NPC168375
0.6842 Remote Similarity NPC600066
0.619 Remote Similarity NPC329263
0.619 Remote Similarity NPC118459
0.619 Remote Similarity NPC309658
0.619 Remote Similarity NPC327698
0.619 Remote Similarity NPC53449
0.6111 Remote Similarity NPC116709
0.6111 Remote Similarity NPC21290
0.6111 Remote Similarity NPC272614
0.6087 Remote Similarity NPC137958
0.6087 Remote Similarity NPC273330
0.5909 Remote Similarity NPC245027
0.5909 Remote Similarity NPC162620
0.5909 Remote Similarity NPC62045
0.5909 Remote Similarity NPC601942
0.5714 Remote Similarity NPC208793
0.5714 Remote Similarity NPC285322
0.5714 Remote Similarity NPC118187
0.5652 Remote Similarity NPC49952
0.5652 Remote Similarity NPC153370
0.5652 Remote Similarity NPC34908
0.5652 Remote Similarity NPC136476
0.56 Remote Similarity NPC279661
0.56 Remote Similarity NPC183845
0.55 Remote Similarity NPC237525
0.55 Remote Similarity NPC326212
0.5417 Remote Similarity NPC167986
0.5417 Remote Similarity NPC140872
0.5417 Remote Similarity NPC93081
0.5417 Remote Similarity NPC291186
0.5417 Remote Similarity NPC600338
0.5238 Remote Similarity NPC132307
0.5238 Remote Similarity NPC126925
0.5217 Remote Similarity NPC84636
0.5217 Remote Similarity NPC226027
0.5217 Remote Similarity NPC174246
0.5217 Remote Similarity NPC43204
0.52 Remote Similarity NPC322532
0.52 Remote Similarity NPC50047
0.52 Remote Similarity NPC608987

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604272 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
0.6111 Remote Similarity NPD8210 Phase 3
0.6111 Remote Similarity NPD8211 Approved
0.6087 Remote Similarity NPD8872 Phase 3
0.5909 Remote Similarity NPD9018 Phase 3
0.5833 Remote Similarity NPD8871 Phase 4
0.5714 Remote Similarity NPD8610 Phase 3
0.5652 Remote Similarity NPD8614 Pre-clinical
0.5417 Remote Similarity NPD8804 Phase 4
0.5417 Remote Similarity NPD8805 Approved
0.5417 Remote Similarity NPD8809 Phase 3
0.5417 Remote Similarity NPD9016 Phase 1
0.5238 Remote Similarity NPD8798 Phase 2
0.5217 Remote Similarity NPD9017 Phase 2
0.52 Remote Similarity NPD9021 Pre-clinical

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