Natural Product: NPC218594

Natural Product IDNPC218594
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DWLJVOJBWLYMJO-HSTADXMGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1651106
PubChem CID 10088615
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 DWLJVOJBWLYMJO-HSTADXMGSA-N
Standard InCHI InChI=1S/C20H24N2O3/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/h3-6,11-13,16,21,23H,7-10H2,1-2H3/t11-,12-,13+,16-,20+/m0/s1
SMILES COC(=O)C1=C2Nc3c([C@@]42[C@@H]2C[C@H]1[C@H](CN2CC4)[C@@H](O)C)cccc3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.18 Volume:   346.876
?
Van der Waals volume.
Dense:   0.981 LogP:   1.826
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.075
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.773
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   61.8
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.805 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.367 Fsp3:   0.55
MCE-18:   126.452
?
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:   0.27 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.644
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.303
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.001 Promiscuous compounds:   0.027

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.342 MDCK Permeability:   -4.897
Pgp-inhibitor:   0.019 Pgp-substrate:   1.0
PAMPA:   0.004
?
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%):   0.282 30% Bioavailability (F30%):   0.953
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.995 MRP1:   0.995
Plasma Protein Binding (PPB):   62.404% Volume Distribution (VD):   0.304
Fu: 37.432%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.019
OATP1B3 inhibitor:   0.001 BCRP inhibitor:   0.075
BSEP inhibitor:   0.501

ADMET: Metabolism

CYP1A2-inhibitor:   0.89 CYP1A2-substrate:   0.059
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.034
CYP2C9-inhibitor:   0.22 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.163 CYP2D6-substrate:   0.699
CYP3A4-inhibitor:   0.971 CYP3A4-substrate:   0.926
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.357
HLM stability:   0.991
?
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):  9.619 Half-life (T1/2):  1.894

ADMET: Toxicity

hERG Blockers:  0.145 hERG Blockers (10um):  0.276
Human Hepatotoxicity (H-HT):  0.846 Drug-induced Liver Injury (DILI):  0.348
AMES Toxicity:  0.568 Rat Oral Acute Toxicity:  0.603
Maximum Recommended Daily Dose:  0.814 Skin Sensitization:  0.979
Carcinogencity:  0.696 Eye Corrosion:  0.0
Eye Irritation:  0.075 Respiratory Toxicity:  0.915
Drug-induced Neurotoxicity:  0.591 Ototoxicity:  0.638
Hematotoxicity:  0.748 Drug-induced Nephrotoxicity:  0.934
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.375 Hek293 Cytotoxicity:  0.529
BCF:   0.625
?
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:   3.325
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.861
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.182
?
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
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]
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]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17493 Alstonia spatulata 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

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 = 8.35 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 NPC218594 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 NPC99043
0.7971 Intermediate Similarity NPC224970
0.7971 Intermediate Similarity NPC167724
0.7971 Intermediate Similarity NPC223595
0.7432 Intermediate Similarity NPC246140
0.7432 Intermediate Similarity NPC1464
0.7432 Intermediate Similarity NPC195787
0.7143 Intermediate Similarity NPC6974
0.6757 Remote Similarity NPC193410
0.6712 Remote Similarity NPC248117
0.6712 Remote Similarity NPC238013
0.6234 Remote Similarity NPC203202
0.6234 Remote Similarity NPC264482
0.6053 Remote Similarity NPC25401
0.6 Remote Similarity NPC138615
0.6 Remote Similarity NPC218733
0.6 Remote Similarity NPC265642
0.6 Remote Similarity NPC132874
0.5875 Remote Similarity NPC600936
0.561 Remote Similarity NPC482064
0.5244 Remote Similarity NPC61013
0.5119 Remote Similarity NPC123241
0.5056 Remote Similarity NPC97584

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC218594 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