Natural Product: NPC198301

Natural Product IDNPC198301
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 N-Methyl-L-Alanine
IUPAC Name (2S)-2-(methylazaniumyl)propanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1234201
PubChem CID 6971259
5288725
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:0004314] Alanine 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 GDFAOVXKHJXLEI-VKHMYHEASA-N
Standard InCHI InChI=1S/C4H9NO2/c1-3(5-2)4(6)7/h3,5H,1-2H3,(H,6,7)/t3-/m0/s1
SMILES C[C@@H](C(=O)O)NC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   103.06 Volume:   103.681
?
Van der Waals volume.
Dense:   0.994 LogP:   -1.029
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.05
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.351
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   1.0
TPSA:   49.33
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.503 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.667 Fsp3:   0.75
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:   0.001 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
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:   0.647 Promiscuous compounds:   0.808

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.827 MDCK Permeability:   -5.06
Pgp-inhibitor:   0.0 Pgp-substrate:   0.239
PAMPA:   0.972
?
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%):   0.002 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.05

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.209 MRP1:   0.91
Plasma Protein Binding (PPB):   15.974% Volume Distribution (VD):   0.047
Fu: 82.431%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.907
OATP1B3 inhibitor:   0.892 BCRP inhibitor:   0.001
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.099 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.113 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.015
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.034
?
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):  0.742 Half-life (T1/2):  2.615

ADMET: Toxicity

hERG Blockers:  0.065 hERG Blockers (10um):  0.166
Human Hepatotoxicity (H-HT):  0.768 Drug-induced Liver Injury (DILI):  0.081
AMES Toxicity:  0.11 Rat Oral Acute Toxicity:  0.168
Maximum Recommended Daily Dose:  0.437 Skin Sensitization:  0.676
Carcinogencity:  0.095 Eye Corrosion:  0.748
Eye Irritation:  0.968 Respiratory Toxicity:  0.347
Drug-induced Neurotoxicity:  0.33 Ototoxicity:  0.413
Hematotoxicity:  0.364 Drug-induced Nephrotoxicity:  0.8
Genotoxicity:  0.746 RPMI-8226 Immunitoxicity:  0.025
A549 Cytotoxicity:  0.008 Hek293 Cytotoxicity:  0.038
BCF:   0.409
?
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:   2.518
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.346
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.991
?
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
NPO8852 Croton jatrophoides Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[15730253]
NPO8852 Croton jatrophoides Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[16792423]
NPO20987 Penicillium janthinellum Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17555349]
NPO20987 Penicillium janthinellum Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31668073]
NPO20987 Penicillium janthinellum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5116 Fagara nitida n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO12706 Dichapetalum cymosum Species Dichapetalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6767 Bursa pastoris Species Bursidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8852 Croton jatrophoides Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8219 Kielmeyera speciosa Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20987 Penicillium janthinellum Species Aspergillaceae 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
NPT1006 Individual protein Proton-coupled amino acid transporter 1 Homo sapiens Ki = 2200000.0 nM PMID[21955456]
NPT1006 Individual protein Proton-coupled amino acid transporter 1 Homo sapiens pKi = -0.34 mM PMID[21955456]

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 NPC198301 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
0.6875 Remote Similarity NPC116709
0.6875 Remote Similarity NPC21290
0.6875 Remote Similarity NPC272614
0.6111 Remote Similarity NPC601351
0.5789 Remote Similarity NPC63621
0.5789 Remote Similarity NPC132307
0.5789 Remote Similarity NPC126925
0.5789 Remote Similarity NPC326992
0.5789 Remote Similarity NPC121517
0.5789 Remote Similarity NPC168375
0.5789 Remote Similarity NPC600066
0.5714 Remote Similarity NPC606939
0.55 Remote Similarity NPC208793
0.55 Remote Similarity NPC155156
0.55 Remote Similarity NPC285322
0.55 Remote Similarity NPC118187
0.55 Remote Similarity NPC602396
0.5263 Remote Similarity NPC237525
0.5263 Remote Similarity NPC134570
0.5263 Remote Similarity NPC326212
0.5238 Remote Similarity NPC270805
0.5238 Remote Similarity NPC118459
0.5238 Remote Similarity NPC327698
0.5238 Remote Similarity NPC93888
0.5238 Remote Similarity NPC53449

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC198301 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
0.6875 Remote Similarity NPD8210 Phase 3
0.6875 Remote Similarity NPD8211 Approved
0.5789 Remote Similarity NPD8798 Phase 2
0.55 Remote Similarity NPD8610 Phase 3
0.5238 Remote Similarity NPD8624 Phase 2
0.5238 Remote Similarity NPD8801 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