Natural Product: NPC102815

Natural Product IDNPC102815
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methionine Sulfone
IUPAC Name (2S)-2-azaniumyl-4-methylsulfonylbutanoate
Synonyms L-Methionine Sulfone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL442720
PubChem CID 6994316
445282
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:0002404] Alpha amino acids
                • [CHEMONTID:0004146] L-alpha-amino acids

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 UCUNFLYVYCGDHP-BYPYZUCNSA-N
Standard InCHI InChI=1S/C5H11NO4S/c1-11(9,10)3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1
SMILES CS(=O)(=O)CC[C@@H](C(=O)O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   181.04 Volume:   157.067
?
Van der Waals volume.
Dense:   1.153 LogP:   -2.853
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.796
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.88
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   3.0
TPSA:   97.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   0.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.569 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.664 Fsp3:   0.8
MCE-18:   5.0
?
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:   0.254 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.042
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.02
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.611 Promiscuous compounds:   0.575

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.821 MDCK Permeability:   -4.783
Pgp-inhibitor:   0.0 Pgp-substrate:   0.062
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):   0.001
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.007

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.926
Plasma Protein Binding (PPB):   20.077% Volume Distribution (VD):   -0.602
Fu: 80.212%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.728
OATP1B3 inhibitor:   0.975 BCRP inhibitor:   0.0
BSEP inhibitor:   0.025

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.941 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   1.0 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):  3.207 Half-life (T1/2):  1.497

ADMET: Toxicity

hERG Blockers:  0.007 hERG Blockers (10um):  0.052
Human Hepatotoxicity (H-HT):  0.377 Drug-induced Liver Injury (DILI):  0.361
AMES Toxicity:  0.653 Rat Oral Acute Toxicity:  0.518
Maximum Recommended Daily Dose:  0.096 Skin Sensitization:  0.953
Carcinogencity:  0.142 Eye Corrosion:  0.083
Eye Irritation:  0.213 Respiratory Toxicity:  0.189
Drug-induced Neurotoxicity:  0.533 Ototoxicity:  0.329
Hematotoxicity:  0.278 Drug-induced Nephrotoxicity:  0.985
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.034
A549 Cytotoxicity:  0.003 Hek293 Cytotoxicity:  0.008
BCF:   0.169
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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:   2.281
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.744
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.802
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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
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. PMID[18071251]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. faeces n.a. PMID[18323202]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22874 Bombyx mori Species Bombycidae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Inhibition = 33.0 % PMID[18462943]
NPT2 Others Unspecified n.a. Inhibition = 67.0 % PMID[18462943]

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 NPC102815 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
0.625 Remote Similarity NPC118459
0.625 Remote Similarity NPC327698
0.625 Remote Similarity NPC53449
0.6154 Remote Similarity NPC167986
0.6154 Remote Similarity NPC291186
0.6087 Remote Similarity NPC63621
0.6087 Remote Similarity NPC326992
0.6087 Remote Similarity NPC121517
0.6087 Remote Similarity NPC168375
0.6087 Remote Similarity NPC600066
0.6 Remote Similarity NPC601942
0.5926 Remote Similarity NPC608987
0.56 Remote Similarity NPC309658
0.5556 Remote Similarity NPC140872
0.5556 Remote Similarity NPC93081
0.5455 Remote Similarity NPC116709
0.5455 Remote Similarity NPC21290
0.5455 Remote Similarity NPC272614
0.5385 Remote Similarity NPC245027
0.5385 Remote Similarity NPC162620
0.5385 Remote Similarity NPC62045
0.5172 Remote Similarity NPC279661
0.5172 Remote Similarity NPC183845
0.5172 Remote Similarity NPC324825
0.5172 Remote Similarity NPC112890
0.5172 Remote Similarity NPC316231

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC102815 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
0.6154 Remote Similarity NPD8804 Phase 4
0.6154 Remote Similarity NPD8805 Approved
0.6154 Remote Similarity NPD9016 Phase 1
0.5926 Remote Similarity NPD9021 Pre-clinical
0.5556 Remote Similarity NPD8809 Phase 3
0.5455 Remote Similarity NPD8210 Phase 3
0.5455 Remote Similarity NPD8211 Approved
0.5385 Remote Similarity NPD9018 Phase 3
0.5172 Remote Similarity NPD9044 Phase 4

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