Natural Product: NPC224023

Natural Product IDNPC224023
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 TYZKUSBTFHNPMV-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10085866
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

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 TYZKUSBTFHNPMV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H17NO3/c1-20-16-12-6-7-19-13-8-10-4-2-3-5-11(10)15(14(12)13)17-18(16)22-9-21-17/h2-5,13,19H,6-9H2,1H3
SMILES COc1c2CCNC3Cc4ccccc4-c(c23)c2c1OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   295.12 Volume:   298.651
?
Van der Waals volume.
Dense:   0.988 LogP:   2.514
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.693
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.111
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   39.72
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.878 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.258 Fsp3:   0.333
MCE-18:   82.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.732 Fluc inhibitor:   0.141
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.546
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.404
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.265

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.979 MDCK Permeability:   -4.762
Pgp-inhibitor:   0.32 Pgp-substrate:   0.35
PAMPA:   0.083
?
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):   0.001
20% Bioavailability (F20%):   0.024 30% Bioavailability (F30%):   0.084
50% Bioavailability (F50%):   0.719

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.993 MRP1:   0.975
Plasma Protein Binding (PPB):   69.235% Volume Distribution (VD):   0.608
Fu: 32.799%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.212
OATP1B3 inhibitor:   0.509 BCRP inhibitor:   0.043
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.373
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.008
CYP2C9-inhibitor:   0.906 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.71
CYP3A4-inhibitor:   0.994 CYP3A4-substrate:   0.455
CYP2B6-substrate:   0.997 CYP2C8-inhibitor:   0.0
HLM stability:   0.478
?
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):  4.599 Half-life (T1/2):  1.095

ADMET: Toxicity

hERG Blockers:  0.59 hERG Blockers (10um):  0.694
Human Hepatotoxicity (H-HT):  0.724 Drug-induced Liver Injury (DILI):  0.36
AMES Toxicity:  0.801 Rat Oral Acute Toxicity:  0.745
Maximum Recommended Daily Dose:  0.887 Skin Sensitization:  0.949
Carcinogencity:  0.519 Eye Corrosion:  0.002
Eye Irritation:  0.118 Respiratory Toxicity:  0.979
Drug-induced Neurotoxicity:  0.898 Ototoxicity:  0.703
Hematotoxicity:  0.157 Drug-induced Nephrotoxicity:  0.699
Genotoxicity:  0.816 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.121 Hek293 Cytotoxicity:  0.239
BCF:   1.944
?
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:   4.056
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.773
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.879
?
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
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[11575948]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18920 Hexalobus crispiflorus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1106 Artabotrys maingayi Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21320 Artabotrys venustus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1106 Artabotrys maingayi Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18920 Hexalobus crispiflorus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21320 Artabotrys venustus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21320 Artabotrys venustus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28711 Artabotrys hexapetalus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10210 Artabotrys uncinatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18920 Hexalobus crispiflorus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1106 Artabotrys maingayi Species Annonaceae 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 NPC224023 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 NPC112575
0.7377 Intermediate Similarity NPC474506
0.6984 Remote Similarity NPC23219
0.6935 Remote Similarity NPC32413
0.6923 Remote Similarity NPC610325
0.6769 Remote Similarity NPC186546
0.6667 Remote Similarity NPC117717
0.6562 Remote Similarity NPC258695
0.6508 Remote Similarity NPC189470
0.6508 Remote Similarity NPC191213
0.6286 Remote Similarity NPC46990
0.6176 Remote Similarity NPC602079
0.6129 Remote Similarity NPC203784
0.6129 Remote Similarity NPC170503
0.6129 Remote Similarity NPC126519
0.5846 Remote Similarity NPC173416
0.5846 Remote Similarity NPC148709
0.5714 Remote Similarity NPC204947
0.5373 Remote Similarity NPC81247
0.5373 Remote Similarity NPC35627
0.5373 Remote Similarity NPC299687
0.5373 Remote Similarity NPC476573

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC224023 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