Natural Product: NPC606250

Natural Product IDNPC606250
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JZKSIYFJGCTTET-WBUQUAQWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL5177009
PubChem CID n.a.
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 JZKSIYFJGCTTET-WBUQUAQWSA-N
Standard InCHI InChI=1S/C20H24N2O3/c1-3-13-10-22-9-8-16(13)20(12-23,19(24)25-2)18-15(11-22)14-6-4-5-7-17(14)21-18/h3-7,16,21,23H,8-12H2,1-2H3/b13-3-/t16-,20-/m0/s1
SMILES C/C=C1/CN2CC[C@@H]1[C@](CO)(C(=O)OC)c1[nH]c3ccccc3c1C2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.18 Volume:   352.796
?
Van der Waals volume.
Dense:   0.964 LogP:   2.248
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.424
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.067
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   65.56
?
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:   0.651 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.703 Fsp3:   0.45
MCE-18:   78.517
?
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:   0.035 Fluc inhibitor:   0.012
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.533
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.207
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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:   0.495

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.241 MDCK Permeability:   -4.91
Pgp-inhibitor:   0.006 Pgp-substrate:   0.221
PAMPA:   0.234
?
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%):   0.019 30% Bioavailability (F30%):   0.258
50% Bioavailability (F50%):   0.894

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.287 MRP1:   0.978
Plasma Protein Binding (PPB):   83.424% Volume Distribution (VD):   0.464
Fu: 16.178%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.051
BSEP inhibitor:   0.974

ADMET: Metabolism

CYP1A2-inhibitor:   0.906 CYP1A2-substrate:   0.062
CYP2C19-inhibitor:   0.393 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.215 CYP2C9-substrate:   0.841
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.076
CYP3A4-inhibitor:   0.884 CYP3A4-substrate:   0.025
CYP2B6-substrate:   0.064 CYP2C8-inhibitor:   0.798
HLM stability:   0.67
?
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):  10.092 Half-life (T1/2):  1.006

ADMET: Toxicity

hERG Blockers:  0.438 hERG Blockers (10um):  0.277
Human Hepatotoxicity (H-HT):  0.67 Drug-induced Liver Injury (DILI):  0.617
AMES Toxicity:  0.621 Rat Oral Acute Toxicity:  0.918
Maximum Recommended Daily Dose:  0.93 Skin Sensitization:  0.968
Carcinogencity:  0.707 Eye Corrosion:  0.0
Eye Irritation:  0.099 Respiratory Toxicity:  0.997
Drug-induced Neurotoxicity:  0.944 Ototoxicity:  0.593
Hematotoxicity:  0.742 Drug-induced Nephrotoxicity:  0.963
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.183
A549 Cytotoxicity:  0.574 Hek293 Cytotoxicity:  0.778
BCF:   0.824
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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:   3.608
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.105
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.441
?
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
NPO19269 Winchia calophylla n.a. n.a. n.a. n.a. n.a. n.a. PMID[16441061]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[21043460]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19269 Winchia calophylla n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO55331 Tabernaemontana coffeoides Boj. Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42456 Tabernaemontana dichotoma Roxb.ex Wall Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46437 Tabernaemontana citrifolia L. Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42470 Tabernaemontana amblyocarpa Urb. Genus Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19269 Winchia calophylla n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19269 Winchia calophylla n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO19269 Winchia calophylla n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18853 Alstonia scholaris Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC > 128.0 ug.mL-1 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 NPC606250 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 NPC19828
0.6923 Remote Similarity NPC187106
0.6923 Remote Similarity NPC1770
0.5526 Remote Similarity NPC59084
0.5233 Remote Similarity NPC317653

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC606250 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