Natural Product: NPC112224

Natural Product IDNPC112224
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S,3S)-2-Amino-3-Hydroxybutanedioic Acid
IUPAC Name (2S,3S)-2-amino-3-hydroxybutanedioic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1231330
PubChem CID 443239
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:0004317] Aspartic acid 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 YYLQUHNPNCGKJQ-LWMBPPNESA-N
Standard InCHI InChI=1S/C4H7NO5/c5-1(3(7)8)2(6)4(9)10/h1-2,6H,5H2,(H,7,8)(H,9,10)/t1-,2-/m0/s1
SMILES [C@H]([C@@H](C(=O)O)O)(C(=O)O)N

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   149.03 Volume:   127.415
?
Van der Waals volume.
Dense:   1.17 LogP:   -2.821
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.834
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.436
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   2.0
TPSA:   120.85
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   0.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.363 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.194 Fsp3:   0.5
MCE-18:   4.0
?
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:   0.536 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
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:   0.608 Promiscuous compounds:   0.763

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.813 MDCK Permeability:   -3.807
Pgp-inhibitor:   0.0 Pgp-substrate:   0.018
PAMPA:   0.997
?
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):   0.005
20% Bioavailability (F20%):   0.058 30% Bioavailability (F30%):   0.05
50% Bioavailability (F50%):   0.356

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.88
Plasma Protein Binding (PPB):   10.931% Volume Distribution (VD):   -0.577
Fu: 92.966%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.013 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.003
HLM stability:   0.062
?
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):  2.982 Half-life (T1/2):  2.507

ADMET: Toxicity

hERG Blockers:  0.012 hERG Blockers (10um):  0.024
Human Hepatotoxicity (H-HT):  0.274 Drug-induced Liver Injury (DILI):  0.104
AMES Toxicity:  0.26 Rat Oral Acute Toxicity:  0.293
Maximum Recommended Daily Dose:  0.029 Skin Sensitization:  0.566
Carcinogencity:  0.212 Eye Corrosion:  0.588
Eye Irritation:  0.941 Respiratory Toxicity:  0.457
Drug-induced Neurotoxicity:  0.084 Ototoxicity:  0.305
Hematotoxicity:  0.229 Drug-induced Nephrotoxicity:  0.632
Genotoxicity:  0.264 RPMI-8226 Immunitoxicity:  0.02
A549 Cytotoxicity:  0.004 Hek293 Cytotoxicity:  0.008
BCF:   0.102
?
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:   2.553
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.755
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.439
?
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
NPO26394 Sarcodon leucopus Species Thelephoraceae Eukaryota Fruits n.a. n.a. PMID[10757716]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota roots n.a. n.a. PMID[20346658]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. PMID[23439553]
NPO26394 Sarcodon leucopus Species Thelephoraceae Eukaryota n.a. Tibet, China n.a. PMID[24645629]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. tuber n.a. Database[Article]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO26394 Sarcodon leucopus Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6078 Arthrinium phaeospermum Species Apiosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2156 Parkia bicolor Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9261 Ophiopogon japonicus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26394 Sarcodon leucopus Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1574 Penstemon cyathophorus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10357 Krameria sonorae Species Krameriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6078 Arthrinium phaeospermum Species Apiosporaceae 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
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 31.6 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens AC50 = 31.62 nM PubChem BioAssay data set
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens AC50 = 39810.72 nM PubChem BioAssay data set
NPT1519 Individual protein Excitatory amino acid transporter 2 Homo sapiens IC50 = 9600.0 nM PMID[30011368]
NPT1520 Individual protein Excitatory amino acid transporter 1 Homo sapiens IC50 = 3900.0 nM PMID[30011368]
NPT1518 Individual protein Excitatory amino acid transporter 3 Homo sapiens IC50 = 9600.0 nM PMID[30011368]
NPT1520 Individual protein Excitatory amino acid transporter 1 Homo sapiens IC50 = 3890.45 nM PMID[30011368]
NPT1519 Individual protein Excitatory amino acid transporter 2 Homo sapiens IC50 = 9549.93 nM PMID[30011368]
NPT1518 Individual protein Excitatory amino acid transporter 3 Homo sapiens IC50 = 9549.93 nM PMID[30011368]
NPT1520 Individual protein Excitatory amino acid transporter 1 Homo sapiens IC50 = 96000.0 nM PMID[36787643]
NPT1519 Individual protein Excitatory amino acid transporter 2 Homo sapiens IC50 = 31000.0 nM PMID[36787643]
NPT58 Individual protein Bloom syndrome protein Homo sapiens Potency = 28.2 nM PubChem BioAssay data set
NPT22676 Single protein Excitatory amino acid transporter 4 Rattus norvegicus IC50 = 2800.0 nM PMID[30011368]
NPT22676 Single protein Excitatory amino acid transporter 4 Rattus norvegicus IC50 = 2818.38 nM PMID[30011368]
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 3548.1 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 19011.5 nM PubChem BioAssay data set
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 3548.1 nM PubChem BioAssay data set
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 89125.1 nM PubChem BioAssay data set
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 26679.5 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 4107.8 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. Ratio IC50 = 3.1 n.a. PMID[36787643]
NPT30067 Tissue Cerebral cortex Rattus norvegicus IC50 = 3200.0 nM PMID[36787643]
NPT2 Others Unspecified n.a. Potency n.a. 3981.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 14125.4 nM PubChem BioAssay data set

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 NPC112224 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 NPC43169
1.0 High Similarity NPC327895
0.6522 Remote Similarity NPC13243
0.619 Remote Similarity NPC226265
0.619 Remote Similarity NPC219143
0.619 Remote Similarity NPC254482
0.619 Remote Similarity NPC110533
0.6 Remote Similarity NPC88898
0.6 Remote Similarity NPC106216
0.5909 Remote Similarity NPC270805
0.5909 Remote Similarity NPC317691
0.5909 Remote Similarity NPC93888
0.5789 Remote Similarity NPC307739
0.5789 Remote Similarity NPC116709
0.5789 Remote Similarity NPC76217
0.5789 Remote Similarity NPC21290
0.5789 Remote Similarity NPC272614
0.5789 Remote Similarity NPC178595
0.55 Remote Similarity NPC100742
0.55 Remote Similarity NPC97444
0.55 Remote Similarity NPC24751
0.5417 Remote Similarity NPC49952
0.5417 Remote Similarity NPC136476
0.5238 Remote Similarity NPC237525
0.5238 Remote Similarity NPC326212
0.52 Remote Similarity NPC190385

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC112224 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
0.619 Remote Similarity NPD8215 Phase 4
0.619 Remote Similarity NPD8216 Phase 3
0.619 Remote Similarity NPD8217 Phase 3
0.5909 Remote Similarity NPD8214 Approved
0.5909 Remote Similarity NPD8624 Phase 2
0.5909 Remote Similarity NPD8801 Phase 4
0.5789 Remote Similarity NPD8202 Phase 4
0.5789 Remote Similarity NPD8205 Phase 4
0.5789 Remote Similarity NPD8210 Phase 3
0.5789 Remote Similarity NPD8211 Approved
0.5652 Remote Similarity NPD8600 Approved
0.55 Remote Similarity NPD8597 Phase 4
0.55 Remote Similarity NPD8605 Phase 4
0.52 Remote Similarity NPD9023 Clinical (unspecified phase)

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