Natural Product: NPC59084

Natural Product IDNPC59084
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Apparicine
IUPAC Name n.a.
Synonyms Apparicine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL285671
PubChem CID 5281349
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0003431] Vallesaman 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 LCVACABZTLIWCE-CRAFIKPXSA-N
Standard InCHI InChI=1S/C18H20N2/c1-3-13-10-20-9-8-14(13)12(2)18-16(11-20)15-6-4-5-7-17(15)19-18/h3-7,14,19H,2,8-11H2,1H3/b13-3-/t14-/m1/s1
SMILES C/C=C1/CN2CC[C@@H]1C(=C)c1c(C2)c2ccccc2[nH]1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   264.16 Volume:   291.833
?
Van der Waals volume.
Dense:   0.905 LogP:   3.298
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.049
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.431
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   19.03
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.713 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.487 Fsp3:   0.333
MCE-18:   68.333
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.355 Fluc inhibitor:   0.066
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.732
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.429
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.444

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.856 MDCK Permeability:   -4.911
Pgp-inhibitor:   0.155 Pgp-substrate:   0.065
PAMPA:   0.008
?
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%):   0.001 30% Bioavailability (F30%):   0.04
50% Bioavailability (F50%):   0.765

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.078 MRP1:   0.867
Plasma Protein Binding (PPB):   92.261% Volume Distribution (VD):   0.504
Fu: 7.764%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.373
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.171
CYP2C19-inhibitor:   0.662 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.14 CYP2C9-substrate:   0.987
CYP2D6-inhibitor:   0.979 CYP2D6-substrate:   0.127
CYP3A4-inhibitor:   0.072 CYP3A4-substrate:   0.214
CYP2B6-substrate:   0.013 CYP2C8-inhibitor:   0.961
HLM stability:   0.885
?
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):  10.204 Half-life (T1/2):  1.639

ADMET: Toxicity

hERG Blockers:  0.607 hERG Blockers (10um):  0.627
Human Hepatotoxicity (H-HT):  0.76 Drug-induced Liver Injury (DILI):  0.745
AMES Toxicity:  0.628 Rat Oral Acute Toxicity:  0.978
Maximum Recommended Daily Dose:  0.901 Skin Sensitization:  0.942
Carcinogencity:  0.775 Eye Corrosion:  0.0
Eye Irritation:  0.092 Respiratory Toxicity:  0.996
Drug-induced Neurotoxicity:  0.954 Ototoxicity:  0.449
Hematotoxicity:  0.597 Drug-induced Nephrotoxicity:  0.9
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.256
A549 Cytotoxicity:  0.51 Hek293 Cytotoxicity:  0.77
BCF:   2.368
?
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:   4.404
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.698
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.24
?
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
NPO33625 Ochrosia moorei Species Apocynaceae Eukaryota stems and leaves Natural Arch National Park, McPherson Range, in South East Queensland 1995-MAR PMID[18412397]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[23944995]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[26231157]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[30169038]
NPO33625 Ochrosia moorei Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23978 Dorstenia zenkeri Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25727 Tabernaemontana divaricata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23773 Holacantha emoryi Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23978 Dorstenia zenkeri Species Moraceae 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
NPT249 Individual protein Glucocorticoid receptor Homo sapiens Activity = 54.0 % PMID[18412397]
NPT967 Individual protein Xanthine dehydrogenase Homo sapiens IC50 = 650.0 nM PMID[34923389]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT168 Cell line P388 Mus musculus ED50 = 3.8 ug ml-1 PMID[34923389]
NPT28438 Unchecked Unchecked n.a. Ki = 2650.0 nM PMID[34923389]

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 NPC59084 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
0.5526 Remote Similarity NPC19828
0.5526 Remote Similarity NPC606250
0.5326 Remote Similarity NPC485961
0.5319 Remote Similarity NPC485888
0.5213 Remote Similarity NPC485956
0.5063 Remote Similarity NPC241024

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59084 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