Natural Product: NPC602310

Natural Product IDNPC602310
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FCEVNJIUIMLVML-DVZMFYIRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1396368
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives

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 FCEVNJIUIMLVML-DVZMFYIRSA-N
Standard InCHI InChI=1S/C18H23NO5/c1-4-12-9-11(2)18(3,22)17(21)23-10-13-5-7-19-8-6-14(15(13)19)24-16(12)20/h4-5,14-15,22H,2,6-10H2,1,3H3/b12-4+/t14-,15-,18+/m1/s1
SMILES C=C1C/C(=CC)C(=O)O[C@@H]2CCN3CC=C(COC(=O)[C@@]1(C)O)[C@H]23

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   333.16 Volume:   335.98
?
Van der Waals volume.
Dense:   0.992 LogP:   0.586
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.973
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.461
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   23.0
TPSA:   76.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.407 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.131 Fsp3:   0.556
MCE-18:   51.429
?
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:   0.041 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.071
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.106
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.009 Promiscuous compounds:   0.488

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.072 MDCK Permeability:   -4.816
Pgp-inhibitor:   0.0 Pgp-substrate:   0.372
PAMPA:   0.848
?
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%):   0.377 30% Bioavailability (F30%):   0.599
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.976
Plasma Protein Binding (PPB):   73.444% Volume Distribution (VD):   0.321
Fu: 25.782%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.816
OATP1B3 inhibitor:   0.949 BCRP inhibitor:   0.027
BSEP inhibitor:   0.776

ADMET: Metabolism

CYP1A2-inhibitor:   0.925 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.019
CYP3A4-inhibitor:   0.765 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.108
HLM stability:   0.266
?
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):  7.584 Half-life (T1/2):  2.304

ADMET: Toxicity

hERG Blockers:  0.085 hERG Blockers (10um):  0.111
Human Hepatotoxicity (H-HT):  0.807 Drug-induced Liver Injury (DILI):  0.593
AMES Toxicity:  0.766 Rat Oral Acute Toxicity:  0.637
Maximum Recommended Daily Dose:  0.984 Skin Sensitization:  1.0
Carcinogencity:  0.976 Eye Corrosion:  0.0
Eye Irritation:  0.011 Respiratory Toxicity:  0.253
Drug-induced Neurotoxicity:  0.671 Ototoxicity:  0.428
Hematotoxicity:  0.628 Drug-induced Nephrotoxicity:  0.989
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.501
A549 Cytotoxicity:  0.296 Hek293 Cytotoxicity:  0.816
BCF:   0.71
?
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:   4.925
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.323
?
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
NPO18591 Senecio vulgaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52875 Adenostyles alliariae (Gouan.) A. Kerner Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52019 Adenostyles glabra (Mill.) DC. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54089 Adenostyles leucophylla (Willd.) Rchb. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO59088 Senecio pterophorus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO55784 Senecio vernalis Waldst. & Kit. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO62529 Senecio vulgaris L. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18591 Senecio vulgaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18591 Senecio vulgaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18591 Senecio vulgaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18591 Senecio vulgaris Species Asteraceae 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
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens Potency = 2511.9 nM PubChem BioAssay data set
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens AC50 = 12589.25 nM PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 17782.8 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 11220.2 nM PubChem BioAssay data set

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 NPC602310 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 NPC47857
1.0 High Similarity NPC181510
1.0 High Similarity NPC168758
0.7931 Intermediate Similarity NPC130124
0.7931 Intermediate Similarity NPC193471
0.7258 Intermediate Similarity NPC201889
0.7258 Intermediate Similarity NPC106791
0.7258 Intermediate Similarity NPC607716
0.7049 Intermediate Similarity NPC608663
0.6935 Remote Similarity NPC608751
0.6825 Remote Similarity NPC609037
0.6462 Remote Similarity NPC23963
0.6462 Remote Similarity NPC608959
0.6349 Remote Similarity NPC30911
0.6349 Remote Similarity NPC608092
0.6176 Remote Similarity NPC600980
0.597 Remote Similarity NPC316984
0.5072 Remote Similarity NPC610562

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602310 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
0.6349 Remote Similarity NPD2204 Approved

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