Natural Product: NPC600171

Natural Product IDNPC600171
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JHUGCRSKMUFKHR-UUOKFMHZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3250749
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 JHUGCRSKMUFKHR-UUOKFMHZSA-N
Standard InCHI InChI=1S/C10H13ClN6O6S/c11-10-15-7(12)4-8(16-10)17(2-14-4)9-6(19)5(18)3(23-9)1-22-24(13,20)21/h2-3,5-6,9,18-19H,1H2,(H2,12,15,16)(H2,13,20,21)/t3-,5-,6-,9-/m1/s1
SMILES Nc1nc(Cl)nc2c1ncn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   380.03 Volume:   297.743
?
Van der Waals volume.
Dense:   1.276 LogP:   -0.691
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.099
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.78
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   188.7
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   14.0

MedChem Properties

QED Drug-Likeness Score:   0.427 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.937 Fsp3:   0.5
MCE-18:   74.2
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.156 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.313
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.026
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.082 Promiscuous compounds:   0.132

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.922 MDCK Permeability:   -4.769
Pgp-inhibitor:   0.0 Pgp-substrate:   0.003
PAMPA:   0.902
?
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):   0.027
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.095
50% Bioavailability (F50%):   0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.224 MRP1:   0.23
Plasma Protein Binding (PPB):   45.473% Volume Distribution (VD):   0.331
Fu: 48.424%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.044 CYP3A4-substrate:   0.009
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.006
HLM stability:   0.013
?
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):  6.031 Half-life (T1/2):  2.011

ADMET: Toxicity

hERG Blockers:  0.057 hERG Blockers (10um):  0.181
Human Hepatotoxicity (H-HT):  0.985 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  0.953 Rat Oral Acute Toxicity:  0.207
Maximum Recommended Daily Dose:  0.741 Skin Sensitization:  0.281
Carcinogencity:  0.513 Eye Corrosion:  0.0
Eye Irritation:  0.042 Respiratory Toxicity:  0.086
Drug-induced Neurotoxicity:  0.702 Ototoxicity:  0.948
Hematotoxicity:  0.78 Drug-induced Nephrotoxicity:  0.483
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.248
A549 Cytotoxicity:  0.005 Hek293 Cytotoxicity:  0.387
BCF:   0.12
?
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:   2.609
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.171
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.135
?
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]
NPO47975 Streptomyces rishiriensis subsp. 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
NPT233 Individual protein Carbonic anhydrase II Homo sapiens Ki = 65.2 nM PMID[29685656]
NPT1062 Individual protein Carbonic anhydrase IV Homo sapiens Ki = 234.0 nM PMID[29685656]
NPT948 Individual protein Carbonic anhydrase IX Homo sapiens Ki = 143.0 nM PMID[29685656]
NPT947 Individual protein Carbonic anhydrase I Homo sapiens Ki = 167.0 nM PMID[29685656]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT71 Cell line HEK293 Homo sapiens CC50 < 150.0 nM PMID[29685656]
NPT28797 Organism Cryptococcus neoformans Cryptococcus neoformans Activity <= 50.0 % PMID[29685656]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition n.a. n.a. % PMID[671448]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae Activity <= 50.0 % PMID[29685656]
NPT20 Organism Candida albicans Candida albicans Activity <= 50.0 % PMID[29685656]
NPT19 Organism Escherichia coli Escherichia coli MIC = 5000.0 nM PMID[29685656]
NPT19 Organism Escherichia coli Escherichia coli Activity > 50.0 % PMID[29685656]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 20000.0 nM PMID[29685656]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus Activity <= 50.0 % PMID[29685656]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa Activity <= 50.0 % PMID[29685656]
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii Activity <= 50.0 % PMID[29685656]

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
- Mus musculus LD50 = 3.4 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 NPC600171 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 NPC472816
0.7857 Intermediate Similarity NPC611003
0.7258 Intermediate Similarity NPC269827
0.6056 Remote Similarity NPC185991
0.6056 Remote Similarity NPC321814
0.5882 Remote Similarity NPC599876
0.5797 Remote Similarity NPC136349
0.5797 Remote Similarity NPC219313
0.5733 Remote Similarity NPC324198
0.5733 Remote Similarity NPC326529
0.5733 Remote Similarity NPC319100
0.5658 Remote Similarity NPC130586
0.5513 Remote Similarity NPC174802
0.5443 Remote Similarity NPC606410
0.5375 Remote Similarity NPC316618
0.5375 Remote Similarity NPC323091
0.5333 Remote Similarity NPC328479

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC600171 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
0.8413 Intermediate Similarity NPD242 Phase 4
0.7258 Intermediate Similarity NPD195 Approved
0.6056 Remote Similarity NPD283 Phase 4
0.5882 Remote Similarity NPD185 Phase 4
0.5797 Remote Similarity NPD548 Clinical (unspecified phase)
0.5571 Remote Similarity NPD166 Phase 4
0.5513 Remote Similarity NPD339 Phase 2
0.5467 Remote Similarity NPD4171 Clinical (unspecified phase)
0.5325 Remote Similarity NPD338 Approved

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