Natural Product: NPC208021

Natural Product IDNPC208021
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Propylformate
IUPAC Name propyl formate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2270393
PubChem CID 8073
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0001093] Carboxylic acid derivatives
          • [CHEMONTID:0001238] Carboxylic acid esters

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 KFNNIILCVOLYIR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C4H8O2/c1-2-3-6-4-5/h4H,2-3H2,1H3
SMILES CCCOC=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   88.05 Volume:   92.684
?
Van der Waals volume.
Dense:   0.95 LogP:   1.029
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.063
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.482
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   1.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.372 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.706 Fsp3:   0.75
MCE-18:   0.0
?
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:   0.008 Fluc inhibitor:   0.161
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
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:   1.0 Promiscuous compounds:   0.087

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.431 MDCK Permeability:   -4.469
Pgp-inhibitor:   0.309 Pgp-substrate:   0.271
PAMPA:   0.271
?
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):   0.194
20% Bioavailability (F20%):   0.477 30% Bioavailability (F30%):   0.458
50% Bioavailability (F50%):   0.352

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.669 MRP1:   0.653
Plasma Protein Binding (PPB):   14.693% Volume Distribution (VD):   -0.114
Fu: 84.204%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.494
OATP1B3 inhibitor:   0.602 BCRP inhibitor:   0.087
BSEP inhibitor:   0.826

ADMET: Metabolism

CYP1A2-inhibitor:   0.032 CYP1A2-substrate:   0.357
CYP2C19-inhibitor:   0.174 CYP2C19-substrate:   0.137
CYP2C9-inhibitor:   0.852 CYP2C9-substrate:   0.042
CYP2D6-inhibitor:   0.368 CYP2D6-substrate:   0.499
CYP3A4-inhibitor:   0.136 CYP3A4-substrate:   0.013
CYP2B6-substrate:   0.059 CYP2C8-inhibitor:   0.226
HLM stability:   0.499
?
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):  9.224 Half-life (T1/2):  0.758

ADMET: Toxicity

hERG Blockers:  0.137 hERG Blockers (10um):  0.639
Human Hepatotoxicity (H-HT):  0.022 Drug-induced Liver Injury (DILI):  0.213
AMES Toxicity:  0.078 Rat Oral Acute Toxicity:  0.042
Maximum Recommended Daily Dose:  0.026 Skin Sensitization:  0.374
Carcinogencity:  0.577 Eye Corrosion:  0.988
Eye Irritation:  0.999 Respiratory Toxicity:  0.087
Drug-induced Neurotoxicity:  0.024 Ototoxicity:  0.1
Hematotoxicity:  0.035 Drug-induced Nephrotoxicity:  0.041
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.026
A549 Cytotoxicity:  0.008 Hek293 Cytotoxicity:  0.02
BCF:   0.163
?
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:   1.908
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.03
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.577
?
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
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota Flowers Tantempango, Hidalgo, Mexico 2019-May DOI[10.1007/s11130-020-00822-2]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. PMID[16297615]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. whole plant n.a. PMID[18543151]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. PMID[24358188]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. PMID[8778246]
NPO2837 Aloe spicata Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14763 Aloe ferox Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2997 Aloe africana Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14763 Aloe ferox Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14763 Aloe ferox Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14763 Aloe ferox Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2997 Aloe africana Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2837 Aloe spicata Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14763 Aloe ferox Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11578 Aloe vera Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2997 Aloe africana Species Xanthorrhoeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14763 Aloe ferox Species Asphodelaceae 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
NPT2 Others Unspecified n.a. Inhibition < 8.0 % PMID[19278021]

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
- Rattus norvegicus LD50 = 3980.0 mg/kg ToxVal
- Mus musculus LD50 = 3400.0 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 NPC208021 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
0.7059 Intermediate Similarity NPC8368
0.6 Remote Similarity NPC159398
0.5714 Remote Similarity NPC147054
0.5294 Remote Similarity NPC110107

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC208021 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