Natural Product: NPC474325

Natural Product IDNPC474325
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UEHWEXPUCDLSTI-NOENWEJRSA-N
IUPAC Name n.a.
Synonyms 1-O-Propanoyllycorine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465296
PubChem CID 44570339
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001775] Amaryllidaceae alkaloids
        • [CHEMONTID:0004120] Lycorine-type amaryllidaceae alkaloids

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 UEHWEXPUCDLSTI-NOENWEJRSA-N
Standard InCHI InChI=1S/C19H21NO5/c1-2-16(22)25-19-13(21)5-10-3-4-20-8-11-6-14-15(24-9-23-14)7-12(11)17(19)18(10)20/h5-7,13,17-19,21H,2-4,8-9H2,1H3/t13-,17-,18+,19+/m0/s1
SMILES CCC(=O)OC1C(C=C2CCN3C2C1C4=CC5=C(C=C4C3)OCO5)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   343.14 Volume:   336.163
?
Van der Waals volume.
Dense:   1.021 LogP:   1.576
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.812
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.758
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   68.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.651 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.248 Fsp3:   0.526
MCE-18:   92.345
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.15 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.499
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.129
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.001

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.801 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.001 Pgp-substrate:   0.693
PAMPA:   0.57
?
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):   0.003
20% Bioavailability (F20%):   0.06 30% Bioavailability (F30%):   0.014
50% Bioavailability (F50%):   0.642

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.97 MRP1:   0.981
Plasma Protein Binding (PPB):   54.574% Volume Distribution (VD):   0.025
Fu: 47.243%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.021
OATP1B3 inhibitor:   0.212 BCRP inhibitor:   0.004
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.581 CYP1A2-substrate:   0.021
CYP2C19-inhibitor:   0.964 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.597
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.656
CYP2B6-substrate:   0.904 CYP2C8-inhibitor:   0.01
HLM stability:   0.795
?
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):  8.816 Half-life (T1/2):  1.438

ADMET: Toxicity

hERG Blockers:  0.119 hERG Blockers (10um):  0.494
Human Hepatotoxicity (H-HT):  0.416 Drug-induced Liver Injury (DILI):  0.339
AMES Toxicity:  0.725 Rat Oral Acute Toxicity:  0.587
Maximum Recommended Daily Dose:  0.743 Skin Sensitization:  0.293
Carcinogencity:  0.805 Eye Corrosion:  0.0
Eye Irritation:  0.045 Respiratory Toxicity:  0.701
Drug-induced Neurotoxicity:  0.783 Ototoxicity:  0.85
Hematotoxicity:  0.224 Drug-induced Nephrotoxicity:  0.365
Genotoxicity:  0.981 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.052 Hek293 Cytotoxicity:  0.296
BCF:   0.799
?
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:   3.486
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.292
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.425
?
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
NPO25024 Lycoris traubii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[19013823]
NPO25024 Lycoris traubii Species Amaryllidaceae 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
NPT171 Cell line MRC5 Homo sapiens IC50 = 4.99 ug.mL-1 PMID[20729083]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 0.3 ug.mL-1 PMID[22222032]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 = 1.34 ug.mL-1 PMID[12542345]
NPT2 Others Unspecified n.a. Ratio IC50 = 3.7 n.a. PMID[16124779]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 0.37 ug.mL-1 PMID[24460410]
NPT2 Others Unspecified n.a. Ratio IC50 = 13.5 n.a. PMID[8350092]
NPT2 Others Unspecified n.a. Ratio IC50 = 16.6 n.a. PMID[20307077]

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 NPC474325 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
0.9194 High Similarity NPC237044
0.9062 High Similarity NPC475981
0.9062 High Similarity NPC474745
0.8529 High Similarity NPC230098
0.8529 High Similarity NPC479864
0.8056 Intermediate Similarity NPC479866
0.7945 Intermediate Similarity NPC479865
0.7465 Intermediate Similarity NPC479860
0.7222 Intermediate Similarity NPC479867
0.7206 Intermediate Similarity NPC475845
0.6812 Remote Similarity NPC474324
0.6528 Remote Similarity NPC474708
0.6316 Remote Similarity NPC479857
0.6232 Remote Similarity NPC190332
0.6232 Remote Similarity NPC181653
0.6184 Remote Similarity NPC479863
0.6027 Remote Similarity NPC607721
0.5972 Remote Similarity NPC479856
0.5921 Remote Similarity NPC479869
0.5915 Remote Similarity NPC320104
0.5844 Remote Similarity NPC479858
0.5811 Remote Similarity NPC33256
0.5811 Remote Similarity NPC479870
0.5663 Remote Similarity NPC479862
0.557 Remote Similarity NPC479859
0.5488 Remote Similarity NPC479861
0.525 Remote Similarity NPC80472
0.5067 Remote Similarity NPC246597

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474325 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