Natural Product: NPC246757

Natural Product IDNPC246757
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cathinone
IUPAC Name (2S)-2-amino-1-phenylpropan-1-one
Synonyms Cathinone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2104047
PubChem CID 62258
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003670] Aryl ketones
              • [CHEMONTID:0004296] Phenylketones
                • [CHEMONTID:0004298] Alkyl-phenylketones

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 PUAQLLVFLMYYJJ-ZETCQYMHSA-N
Standard InCHI InChI=1S/C9H11NO/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7H,10H2,1H3/t7-/m0/s1
SMILES C[C@@H](C(=O)c1ccccc1)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   149.08 Volume:   164.905
?
Van der Waals volume.
Dense:   0.904 LogP:   1.106
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.012
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.557
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   7.0
TPSA:   43.09
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.642 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.083 Fsp3:   0.222
MCE-18:   12.0
?
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:   0.257 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.052
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.008
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.599 Promiscuous compounds:   0.556

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.054 MDCK Permeability:   -4.28
Pgp-inhibitor:   0.042 Pgp-substrate:   0.42
PAMPA:   0.162
?
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):   0.0
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.011

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.113 MRP1:   0.927
Plasma Protein Binding (PPB):   26.653% Volume Distribution (VD):   0.326
Fu: 67.347%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.609
OATP1B3 inhibitor:   0.931 BCRP inhibitor:   0.006
BSEP inhibitor:   0.89

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.057
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.082
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.303
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.926
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.94
HLM stability:   0.968
?
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):  7.063 Half-life (T1/2):  2.484

ADMET: Toxicity

hERG Blockers:  0.29 hERG Blockers (10um):  0.554
Human Hepatotoxicity (H-HT):  0.916 Drug-induced Liver Injury (DILI):  0.463
AMES Toxicity:  0.733 Rat Oral Acute Toxicity:  0.256
Maximum Recommended Daily Dose:  0.292 Skin Sensitization:  0.819
Carcinogencity:  0.496 Eye Corrosion:  0.593
Eye Irritation:  0.901 Respiratory Toxicity:  0.641
Drug-induced Neurotoxicity:  0.962 Ototoxicity:  0.711
Hematotoxicity:  0.715 Drug-induced Nephrotoxicity:  0.753
Genotoxicity:  0.982 RPMI-8226 Immunitoxicity:  0.035
A549 Cytotoxicity:  0.013 Hek293 Cytotoxicity:  0.038
BCF:   0.393
?
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:   2.859
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.8
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.29
?
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
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. root n.a. PMID[18975262]
NPO28125 Ephedra equisetina Species Ephedraceae Eukaryota n.a. n.a. n.a. PMID[21465337]
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. n.a. n.a. PMID[24333010]
NPO28125 Ephedra equisetina Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21507 Ephedra intermedia Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28125 Ephedra equisetina Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21507 Ephedra intermedia Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28125 Ephedra equisetina Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21507 Ephedra intermedia Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28125 Ephedra equisetina Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28125 Ephedra equisetina Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21507 Ephedra intermedia Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18176 Ephedra sinica Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28125 Ephedra equisetina Species Ephedraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21507 Ephedra intermedia Species Ephedraceae 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
NPT100 Individual protein Glutaminase kidney isoform, mitochondrial Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT1530 Protein family Serotonin (5-HT) receptor Rattus norvegicus Kd = 3019.95 nM PMID[7365744]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20913 Tissue Whole blood Homo sapiens Retention_time = 2.09 min DOI[10.1007/s00044-012-9977-1]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus ED50 = 0.34 mg.kg-1 PMID[28244748]
NPT29 Organism Rattus norvegicus Rattus norvegicus ED50 = 0.17 mg.kg-1 PMID[28244748]
NPT29 Organism Rattus norvegicus Rattus norvegicus ED50 = 0.22 mg.kg-1 PMID[28244748]
NPT29 Organism Rattus norvegicus Rattus norvegicus ED50 = 0.32 mg.kg-1 PMID[28244748]





 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 = 400.0 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 NPC246757 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 NPC291070
0.5652 Remote Similarity NPC2785
0.5417 Remote Similarity NPC418074
0.5385 Remote Similarity NPC285470
0.5385 Remote Similarity NPC190567
0.5385 Remote Similarity NPC300205

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC246757 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
NPD

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