Natural Product: NPC605233

Natural Product IDNPC605233
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PAJPWUMXBYXFCZ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL265325
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 PAJPWUMXBYXFCZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C4H7NO2/c5-4(1-2-4)3(6)7/h1-2,5H2,(H,6,7)
SMILES NC1(C(=O)O)CC1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   101.05 Volume:   95.125
?
Van der Waals volume.
Dense:   1.062 LogP:   -2.873
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.889
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   0.814
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   4.0
TPSA:   63.32
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.47 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.614 Fsp3:   0.75
MCE-18:   13.0
?
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:   0.056 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.026
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.028
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.867 Promiscuous compounds:   0.647

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.108 MDCK Permeability:   -3.97
Pgp-inhibitor:   0.0 Pgp-substrate:   0.038
PAMPA:   0.996
?
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):   0.01
20% Bioavailability (F20%):   0.007 30% Bioavailability (F30%):   0.005
50% Bioavailability (F50%):   0.341

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.683
Plasma Protein Binding (PPB):   9.037% Volume Distribution (VD):   -0.466
Fu: 87.475%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.0
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.018
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.279 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.009
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.079
HLM stability:   0.102
?
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):  0.983 Half-life (T1/2):  2.537

ADMET: Toxicity

hERG Blockers:  0.038 hERG Blockers (10um):  0.167
Human Hepatotoxicity (H-HT):  0.483 Drug-induced Liver Injury (DILI):  0.072
AMES Toxicity:  0.441 Rat Oral Acute Toxicity:  0.385
Maximum Recommended Daily Dose:  0.223 Skin Sensitization:  0.408
Carcinogencity:  0.424 Eye Corrosion:  0.83
Eye Irritation:  0.967 Respiratory Toxicity:  0.758
Drug-induced Neurotoxicity:  0.395 Ototoxicity:  0.282
Hematotoxicity:  0.344 Drug-induced Nephrotoxicity:  0.348
Genotoxicity:  0.231 RPMI-8226 Immunitoxicity:  0.035
A549 Cytotoxicity:  0.018 Hek293 Cytotoxicity:  0.051
BCF:   0.264
?
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:   2.676
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.528
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.093
?
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
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0014-5793(03)00033-4]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/ac991142i]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1034/j.1399-3054.2003.00030.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1046/j.1365-3040.2001.00686.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.274.1.397]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M302362200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M314195200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M411109200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1104/pp.103.022368]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[11005203]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12637544]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12805618]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[14745019]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15280363]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15820655]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15834012]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota aerial parts n.a. n.a. PMID[15844959]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[1684022]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[17611796]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18057039]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18235971]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18318836]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[19521717]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21193570]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21194489]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21395888]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21800258]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23370715]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23950498]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[24163311]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24285094]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[25457500]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[27363486]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[27432888]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[8278506]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46980 Streptomyces sp. NEAU-S7GS2 Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. Database[MetaboLights]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8970 Citrullus lanatus Species Cucurbitaceae 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
NPT210 Individual protein Thyroid stimulating hormone receptor Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 5011.9 nM PubChem BioAssay data set
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 99.32 % PMID[23571415]
NPT95 Individual protein Muscarinic acetylcholine receptor M1 Rattus norvegicus Potency = 28183.8 nM PubChem BioAssay data set
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 125.86 % PMID[23571415]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 1.28 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT21123 Single protein Amino acid transporter Rattus norvegicus Inhibition >= 25.0 % US-8741955-B2
NPT20556 Single protein Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = -4.23 % Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = -14.45 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT29389 Protein complex group Glutamate NMDA receptor Rattus norvegicus Ki = 158.49 nM PMID[19642674]
NPT29389 Protein complex group Glutamate NMDA receptor Rattus norvegicus EC50 = 140.0 nM PMID[7990104]
NPT29389 Protein complex group Glutamate NMDA receptor Rattus norvegicus IC50 = 40.0 nM PMID[7990104]
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 56234.1 nM PubChem BioAssay data set
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 50118.7 nM PubChem BioAssay data set
NPT62 Individual protein 6-phospho-1-fructokinase Trypanosoma brucei Potency n.a. 60119.8 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 7079.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 4.95 % Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 0.08 % Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Potency = 25929.0 nM PubChem BioAssay data set

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus ED50 = 234.0 mg.kg-1 PMID[7990104]





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference
Homo sapiens n.a. CL = 1.5 mL.min-1.kg-1 PMID[15920768]
Canis lupus familiaris n.a. CL = 0.4 mL.min-1.kg-1 PMID[15920768]
Canis lupus familiaris n.a. Vdss = 0.7 L.kg-1 PMID[15920768]
Macaca n.a. CL = 3.1 mL.min-1.kg-1 PMID[15920768]
Rattus norvegicus n.a. CL = 3.2 mL.min-1.kg-1 PMID[15920768]
Rattus norvegicus n.a. Vdss = 0.64 mL/min/kg PMID[15920768]
Macaca n.a. Vdss = 0.72 L.kg-1 PMID[15920768]
Homo sapiens n.a. Vdss = 0.73 L.kg-1 PMID[15920768]





 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 NPC605233 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
0.8235 Intermediate Similarity NPC603299
0.625 Remote Similarity NPC9294
0.5789 Remote Similarity NPC107645
0.5625 Remote Similarity NPC126681
0.5294 Remote Similarity NPC116709
0.5294 Remote Similarity NPC21290
0.5294 Remote Similarity NPC272614
0.5263 Remote Similarity NPC63621
0.5263 Remote Similarity NPC326992
0.5263 Remote Similarity NPC121517
0.5263 Remote Similarity NPC168375
0.5263 Remote Similarity NPC600066
0.52 Remote Similarity NPC608248

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605233 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
0.65 Remote Similarity NPD8850 Approved
0.619 Remote Similarity NPD8946 Approved
0.619 Remote Similarity NPD8947 Approved
0.5625 Remote Similarity NPD7371 Phase 4
0.5294 Remote Similarity NPD8210 Phase 3
0.5294 Remote Similarity NPD8211 Approved
0.52 Remote Similarity NPD8979 Approved
0.52 Remote Similarity NPD8980 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