Natural Product: NPC167724

Natural Product IDNPC167724
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Alstolucine F
IUPAC Name n.a.
Synonyms Alstolucine F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1651104
PubChem CID 10246517
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002749] Strychnos 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 DHAOEWPYRANXCZ-MAOAEMCLSA-N
Standard InCHI InChI=1S/C20H22N2O3/c1-11(23)13-10-22-8-7-20-14-5-3-4-6-15(14)21-18(20)17(19(24)25-2)12(13)9-16(20)22/h3-6,12-13,16,21H,7-10H2,1-2H3/t12-,13+,16-,20+/m0/s1
SMILES CC(=O)[C@H]1CN2CC[C@@]34c5ccccc5NC4=C([C@H]1C[C@H]23)C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.16 Volume:   344.239
?
Van der Waals volume.
Dense:   0.982 LogP:   1.379
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.625
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.456
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   58.64
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.837 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.185 Fsp3:   0.5
MCE-18:   126.933
?
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:   0.092 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.687
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.467
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.08

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.109 MDCK Permeability:   -4.724
Pgp-inhibitor:   0.285 Pgp-substrate:   1.0
PAMPA:   0.0
?
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%):   0.043 30% Bioavailability (F30%):   0.875
50% Bioavailability (F50%):   0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   1.0 MRP1:   0.986
Plasma Protein Binding (PPB):   80.514% Volume Distribution (VD):   0.323
Fu: 19.412%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.0
OATP1B3 inhibitor:   0.0 BCRP inhibitor:   0.009
BSEP inhibitor:   0.766

ADMET: Metabolism

CYP1A2-inhibitor:   0.952 CYP1A2-substrate:   0.304
CYP2C19-inhibitor:   0.995 CYP2C19-substrate:   0.044
CYP2C9-inhibitor:   0.028 CYP2C9-substrate:   0.149
CYP2D6-inhibitor:   0.289 CYP2D6-substrate:   0.43
CYP3A4-inhibitor:   0.95 CYP3A4-substrate:   0.615
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.006
HLM stability:   0.954
?
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):  10.981 Half-life (T1/2):  1.462

ADMET: Toxicity

hERG Blockers:  0.179 hERG Blockers (10um):  0.322
Human Hepatotoxicity (H-HT):  0.813 Drug-induced Liver Injury (DILI):  0.623
AMES Toxicity:  0.375 Rat Oral Acute Toxicity:  0.659
Maximum Recommended Daily Dose:  0.8 Skin Sensitization:  0.897
Carcinogencity:  0.688 Eye Corrosion:  0.001
Eye Irritation:  0.123 Respiratory Toxicity:  0.936
Drug-induced Neurotoxicity:  0.58 Ototoxicity:  0.581
Hematotoxicity:  0.715 Drug-induced Nephrotoxicity:  0.931
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.03
A549 Cytotoxicity:  0.149 Hek293 Cytotoxicity:  0.455
BCF:   0.635
?
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:   3.367
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.754
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.2
?
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
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[21043460]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[21043460]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. stem n.a. PMID[21043460]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. leaf n.a. PMID[21043460]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18853 Alstonia scholaris Species Apocynaceae 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
NPT957 Individual protein Multidrug resistance-associated protein 7 Homo sapiens Inhibition = 40.0 % PMID[25419978]
NPT957 Individual protein Multidrug resistance-associated protein 7 Homo sapiens Inhibition = 50.0 % PMID[25419978]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 25.0 ug.mL-1 PMID[21043460]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 2.61 ug.mL-1 PMID[21043460]

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 NPC167724 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 NPC224970
1.0 High Similarity NPC223595
0.7971 Intermediate Similarity NPC99043
0.7971 Intermediate Similarity NPC218594
0.7361 Intermediate Similarity NPC600936
0.7333 Intermediate Similarity NPC6974
0.726 Intermediate Similarity NPC138615
0.726 Intermediate Similarity NPC218733
0.726 Intermediate Similarity NPC265642
0.726 Intermediate Similarity NPC132874
0.6944 Remote Similarity NPC193410
0.6901 Remote Similarity NPC248117
0.6901 Remote Similarity NPC238013
0.64 Remote Similarity NPC203202
0.64 Remote Similarity NPC264482
0.6216 Remote Similarity NPC25401
0.5875 Remote Similarity NPC246140
0.5875 Remote Similarity NPC1464
0.5875 Remote Similarity NPC195787
0.5375 Remote Similarity NPC61013
0.5366 Remote Similarity NPC482064
0.5244 Remote Similarity NPC123241
0.5119 Remote Similarity NPC159963

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC167724 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