Natural Product: NPC489880

Natural Product IDNPC489880
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 S-Methyl-L-methionine chloride
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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:0004143] Methionine 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 MYGVPKMVGSXPCQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C6H13NO2S.ClH/c1-10(2)4-3-5(7)6(8)9;/h5H,3-4,7H2,1-2H3;1H
SMILES [Cl-].C[S+](C)CCC(N)C(O)=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   164.07 Volume:   158.1
?
Van der Waals volume.
Dense:   1.038 LogP:   -2.176
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.85
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.642
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   1.0
TPSA:   63.32
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.559 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.671 Fsp3:   0.833
MCE-18:   3.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.188 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.536 Promiscuous compounds:   0.327

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.722 MDCK Permeability:   -4.34
Pgp-inhibitor:   0.0 Pgp-substrate:   0.992
PAMPA:   0.993
?
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):   0.833
20% Bioavailability (F20%):   0.717 30% Bioavailability (F30%):   0.935
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.64
Plasma Protein Binding (PPB):   10.978% Volume Distribution (VD):   -0.423
Fu: 92.67%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.24
OATP1B3 inhibitor:   0.503 BCRP inhibitor:   0.002
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.962 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.806 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.001
?
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):  8.26 Half-life (T1/2):  2.0

ADMET: Toxicity

hERG Blockers:  0.005 hERG Blockers (10um):  0.077
Human Hepatotoxicity (H-HT):  0.024 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.101 Rat Oral Acute Toxicity:  0.464
Maximum Recommended Daily Dose:  0.674 Skin Sensitization:  1.0
Carcinogencity:  0.44 Eye Corrosion:  0.72
Eye Irritation:  0.823 Respiratory Toxicity:  0.91
Drug-induced Neurotoxicity:  0.055 Ototoxicity:  0.01
Hematotoxicity:  0.007 Drug-induced Nephrotoxicity:  0.112
Genotoxicity:  0.024 RPMI-8226 Immunitoxicity:  0.01
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.036
BCF:   0.151
?
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:   2.785
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.01
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.25
?
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
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24014097]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24128451]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7576 Brassica oleracea Species Brassicaceae 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
NPO7576 Brassica oleracea Raw Leaf 1.35 0.2 2.5 mg/100g Database [DUKE]

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

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 NPC489880 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
0.6667 Remote Similarity NPC245027
0.6667 Remote Similarity NPC162620
0.6667 Remote Similarity NPC62045
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
0.5714 Remote Similarity NPC102815
0.5556 Remote Similarity NPC140872
0.5556 Remote Similarity NPC93081
0.5556 Remote Similarity NPC600338
0.5455 Remote Similarity NPC116709
0.5455 Remote Similarity NPC21290
0.5455 Remote Similarity NPC272614
0.5417 Remote Similarity NPC132307
0.5417 Remote Similarity NPC126925
0.5385 Remote Similarity NPC84636
0.5385 Remote Similarity NPC226027
0.5385 Remote Similarity NPC174246
0.5385 Remote Similarity NPC43204
0.5357 Remote Similarity NPC608987
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 NPC489880 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
0.9545 High Similarity NPD9021 Pre-clinical
0.6667 Remote Similarity NPD9018 Phase 3
0.6154 Remote Similarity NPD8804 Phase 4
0.6154 Remote Similarity NPD8805 Approved
0.6154 Remote Similarity NPD9016 Phase 1
0.5556 Remote Similarity NPD8809 Phase 3
0.5455 Remote Similarity NPD8210 Phase 3
0.5455 Remote Similarity NPD8211 Approved
0.5417 Remote Similarity NPD8798 Phase 2
0.5385 Remote Similarity NPD9017 Phase 2
0.5357 Remote Similarity NPD9020 Approved
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