Natural Product: NPC295652

Natural Product IDNPC295652
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ONTAOGAXMOTXQW-DZSWIPIPSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 440894
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:0002404] Alpha amino acids
                • [CHEMONTID:0004146] L-alpha-amino acids

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 ONTAOGAXMOTXQW-DZSWIPIPSA-N
Standard InCHI InChI=1S/C6H11NO5/c1-6(12,5(10)11)2-3(7)4(8)9/h3,12H,2,7H2,1H3,(H,8,9)(H,10,11)/t3-,6-/m0/s1
SMILES C[C@](C[C@@H](C(=O)O)N)(C(=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   177.06 Volume:   162.007
?
Van der Waals volume.
Dense:   1.093 LogP:   -2.731
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.739
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.998
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 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:   0.42 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.43 Fsp3:   0.667
MCE-18:   6.0
?
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:   0.555 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.034
?
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:   0.425 Promiscuous compounds:   0.16

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.041 MDCK Permeability:   -4.649
Pgp-inhibitor:   0.0 Pgp-substrate:   0.077
PAMPA:   1.0
?
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%):   0.002 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.332

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.96
Plasma Protein Binding (PPB):   13.753% Volume Distribution (VD):   -0.535
Fu: 87.206%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.82
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.0
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.185 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.005
HLM stability:   0.002
?
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):  1.797 Half-life (T1/2):  2.639

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.012
Human Hepatotoxicity (H-HT):  0.623 Drug-induced Liver Injury (DILI):  0.167
AMES Toxicity:  0.403 Rat Oral Acute Toxicity:  0.262
Maximum Recommended Daily Dose:  0.241 Skin Sensitization:  0.842
Carcinogencity:  0.507 Eye Corrosion:  0.2
Eye Irritation:  0.599 Respiratory Toxicity:  0.572
Drug-induced Neurotoxicity:  0.24 Ototoxicity:  0.587
Hematotoxicity:  0.119 Drug-induced Nephrotoxicity:  0.942
Genotoxicity:  0.322 RPMI-8226 Immunitoxicity:  0.074
A549 Cytotoxicity:  0.032 Hek293 Cytotoxicity:  0.018
BCF:   0.193
?
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:   2.635
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.793
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.298
?
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
NPO22673 Turraea wakefieldii Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22790 Haplophyllum acutifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22737 Caylusea abyssinica Species Resedaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23087 Thryptomene saxicola Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22790 Haplophyllum acutifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22790 Haplophyllum acutifolium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22673 Turraea wakefieldii Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19603 Heracleum dissectum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23087 Thryptomene saxicola Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22737 Caylusea abyssinica Species Resedaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18942 Artemisia borealis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13347 Fagara tingoassuiba n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO22673 Turraea wakefieldii Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22790 Haplophyllum acutifolium Species Rutaceae 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

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 NPC295652 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
0.5833 Remote Similarity NPC63621
0.5833 Remote Similarity NPC326992
0.5833 Remote Similarity NPC121517
0.5833 Remote Similarity NPC168375
0.5833 Remote Similarity NPC600066
0.5556 Remote Similarity NPC49952
0.5556 Remote Similarity NPC136476
0.5517 Remote Similarity NPC88898
0.5517 Remote Similarity NPC106216
0.5385 Remote Similarity NPC270805
0.5385 Remote Similarity NPC118459
0.5385 Remote Similarity NPC327698
0.5385 Remote Similarity NPC93888
0.5385 Remote Similarity NPC53449
0.5217 Remote Similarity NPC116709
0.5217 Remote Similarity NPC212144
0.5217 Remote Similarity NPC21290
0.5217 Remote Similarity NPC272614
0.5185 Remote Similarity NPC245027
0.5185 Remote Similarity NPC43169
0.5185 Remote Similarity NPC162620
0.5185 Remote Similarity NPC327895
0.5185 Remote Similarity NPC62045
0.5185 Remote Similarity NPC112224

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC295652 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
0.5385 Remote Similarity NPD8624 Phase 2
0.5385 Remote Similarity NPD8801 Phase 4
0.5217 Remote Similarity NPD8210 Phase 3
0.5217 Remote Similarity NPD8211 Approved
0.5185 Remote Similarity NPD9018 Phase 3

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