Natural Product: NPC483027

Natural Product IDNPC483027
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AZZMGZXNTDTSME-JUZDKLSSSA-M
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10695961
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000160] Lactams
        • [CHEMONTID:0000162] Beta lactams
          • [CHEMONTID:0000168] Cephems
            • [CHEMONTID:0000173] Cephalosporins
              • [CHEMONTID:0004411] Cephalosporin 3'-esters

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 AZZMGZXNTDTSME-JUZDKLSSSA-M
Standard InCHI InChI=1S/C16H17N5O7S2.Na/c1-6(22)28-3-7-4-29-14-10(13(24)21(14)11(7)15(25)26)19-12(23)9(20-27-2)8-5-30-16(17)18-8;/h5,10,14H,3-4H2,1-2H3,(H2,17,18)(H,19,23)(H,25,26);/q;+1/p-1/b20-9-;/t10-,14-;/m1./s1
SMILES CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@H]([C@H]2SC1)N=C(/C(=NOC)/c1csc(=N)[nH]1)[O-].[Na+]

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   454.05 Volume:   390.746
?
Van der Waals volume.
Dense:   1.162 LogP:   -0.52
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.019
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.691
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   20.0
TPSA:   180.56
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   14.0

MedChem Properties

QED Drug-Likeness Score:   0.152 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.736 Fsp3:   0.375
MCE-18:   68.727
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.259 Fluc inhibitor:   0.022
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.015
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.078
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.068 Promiscuous compounds:   0.293

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.157 MDCK Permeability:   -5.372
Pgp-inhibitor:   0.972 Pgp-substrate:   0.656
PAMPA:   0.711
?
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):   0.981
20% Bioavailability (F20%):   0.997 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.751
Plasma Protein Binding (PPB):   38.192% Volume Distribution (VD):   -0.69
Fu: 62.611%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.854
OATP1B3 inhibitor:   0.933 BCRP inhibitor:   0.007
BSEP inhibitor:   0.805

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.024 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.044
HLM stability:   0.587
?
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):  1.912 Half-life (T1/2):  1.311

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.012
Human Hepatotoxicity (H-HT):  0.995 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  0.136 Rat Oral Acute Toxicity:  0.043
Maximum Recommended Daily Dose:  0.0 Skin Sensitization:  1.0
Carcinogencity:  0.18 Eye Corrosion:  0.0
Eye Irritation:  0.233 Respiratory Toxicity:  0.112
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.978
Hematotoxicity:  0.572 Drug-induced Nephrotoxicity:  0.997
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.004
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.006
BCF:   0.386
?
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:   3.144
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.731
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.075
?
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
NPO21963 Hypericum japonicum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[11914965]
NPO21963 Hypericum japonicum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[27116034]
NPO21963 Hypericum japonicum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[29667821]
NPO21963 Hypericum japonicum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21963 Hypericum japonicum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21963 Hypericum japonicum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21963 Hypericum japonicum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21963 Hypericum japonicum Species Hypericaceae 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
NPT1249 Individual protein Canalicular multispecific organic anion transporter 2 Homo sapiens IC50 > 133000.0 nM PMID[23956101]
NPT1028 Individual protein Multidrug resistance-associated protein 4 Homo sapiens IC50 = 24000.0 nM PMID[23956101]
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 119.18 % PMID[23571415]
NPT713 Individual protein Bile salt export pump Homo sapiens IC50 > 133000.0 nM PMID[23956101]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 104.13 % PMID[23571415]
NPT612 Individual protein Canalicular multispecific organic anion transporter 1 Homo sapiens IC50 > 133000.0 nM PMID[23956101]
NPT20556 Single protein Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = 5.064 % DOI[10.6019/CHEMBL4495564]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1122 Organism Haemophilus influenzae Haemophilus influenzae MIC < 0.03 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT172 Organism Proteus mirabilis Proteus mirabilis MIC < 0.03 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT1118 Organism Streptococcus pneumoniae Streptococcus pneumoniae MIC < 0.03 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT1118 Organism Streptococcus pneumoniae Streptococcus pneumoniae MIC = 2.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT331 Organism Ralstonia solanacearum Ralstonia solanacearum MIC = 2.0 ug.mL-1 PMID[30097370]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC = 3300.0 nM PMID[29667821]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 13.83 % DOI[10.21203/rs.3.rs-23951/v1]
NPT331 Organism Ralstonia solanacearum Ralstonia solanacearum MIC = 3125.0 nM PMID[30317023]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 0.02 % DOI[10.6019/CHEMBL4495565]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC = 0.06 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT2710 Organism Streptococcus agalactiae Streptococcus agalactiae MIC = 0.12 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT1228 Organism Streptococcus pyogenes Streptococcus pyogenes MIC < 0.03 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 2.0 ug.mL-1 PMID[30097370]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 3125.0 nM PMID[30317023]
NPT19 Organism Escherichia coli Escherichia coli MIC < 0.03 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT19 Organism Escherichia coli Escherichia coli MIC = 0.5 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT3495 Organism Morganella morganii Morganella morganii MIC = 2.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 16.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC > 64.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 2.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 4.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 1.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 1.0 ug.mL-1 PMID[30097370]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 16.0 ug.mL-1 PMID[30097370]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 3300.0 nM PMID[29667821]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC = 400.0 nM PMID[29667821]
NPT19 Organism Escherichia coli Escherichia coli MIC = 400.0 nM PMID[29667821]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 25000.0 nM PMID[30317023]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 1560.0 nM PMID[30317023]
NPT19 Organism Escherichia coli Escherichia coli MIC = 1560.0 nM PMID[30317023]
NPT1121 Organism Moraxella catarrhalis Moraxella catarrhalis MIC = 0.25 ug.mL-1 DOI[10.1016/S0960-894X(01)80928-8]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 16.0 ug.mL-1 PMID[30097370]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 25000.0 nM PMID[30317023]

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
- Rattus norvegicus LD50 > 20000.0 mg/kg ToxVal
- Mus musculus LD50 > 20000.0 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 NPC483027 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
0.75 Intermediate Similarity NPC478434
0.505 Remote Similarity NPC486882

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC483027 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 NPD2023 Approved
0.7531 Intermediate Similarity NPD1963 Approved
0.75 Intermediate Similarity NPD2025 Phase 4
0.7105 Intermediate Similarity NPD984 Approved
0.6778 Remote Similarity NPD3877 Approved
0.6667 Remote Similarity NPD1665 Phase 4
0.663 Remote Similarity NPD2857 Approved
0.6333 Remote Similarity NPD4961 Approved
0.6277 Remote Similarity NPD3491 Approved
0.6145 Remote Similarity NPD2065 Discontinued
0.5833 Remote Similarity NPD2024 Approved
0.5714 Remote Similarity NPD3291 Phase 2
0.5577 Remote Similarity NPD4337 Clinical (unspecified phase)
0.5464 Remote Similarity NPD3876 Phase 4
0.5426 Remote Similarity NPD2027 Phase 4
0.5368 Remote Similarity NPD20 Approved
0.5281 Remote Similarity NPD1959 Phase 4
0.5281 Remote Similarity NPD1985 Approved
0.5281 Remote Similarity NPD1987 Approved
0.5244 Remote Similarity NPD2891 Phase 4
0.5176 Remote Similarity NPD985 Phase 4
0.5119 Remote Similarity NPD1978 Approved
0.5102 Remote Similarity NPD3332 Phase 2
0.5102 Remote Similarity NPD3333 Approved
0.5057 Remote Similarity NPD1263 Phase 4
0.505 Remote Similarity NPD2858 Phase 4
0.505 Remote Similarity NPD3966 Clinical (unspecified phase)

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