Natural Product: NPC243635

Natural Product IDNPC243635
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sparteine
IUPAC Name n.a.
Synonyms Sparteine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL412873
PubChem CID 7014
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002719] Lupin alkaloids
        • [CHEMONTID:0001795] Sparteine, lupanine, and related 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 SLRCCWJSBJZJBV-TUVASFSCSA-N
Standard InCHI InChI=1S/C15H26N2/c1-3-7-16-11-13-9-12(14(16)5-1)10-17-8-4-2-6-15(13)17/h12-15H,1-11H2/t12-,13-,14-,15+/m1/s1
SMILES C1CCN2C[C@H]3C[C@H](CN4CCCC[C@@H]34)[C@H]2C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   234.21 Volume:   255.764
?
Van der Waals volume.
Dense:   0.916 LogP:   1.814
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.86
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.049
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   6.48
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.635 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.281 Fsp3:   1.0
MCE-18:   54.0
?
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:   0.076 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.103
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.022 Promiscuous compounds:   0.13

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.938 MDCK Permeability:   -4.878
Pgp-inhibitor:   0.016 Pgp-substrate:   0.148
PAMPA:   0.0
?
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%):   0.003
50% Bioavailability (F50%):   0.007

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.062 MRP1:   0.246
Plasma Protein Binding (PPB):   44.207% Volume Distribution (VD):   0.575
Fu: 49.203%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.731
BSEP inhibitor:   0.85

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.12
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.128
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.898
?
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):  5.744 Half-life (T1/2):  1.545

ADMET: Toxicity

hERG Blockers:  0.369 hERG Blockers (10um):  0.56
Human Hepatotoxicity (H-HT):  0.491 Drug-induced Liver Injury (DILI):  0.139
AMES Toxicity:  0.403 Rat Oral Acute Toxicity:  0.524
Maximum Recommended Daily Dose:  0.469 Skin Sensitization:  0.774
Carcinogencity:  0.357 Eye Corrosion:  0.731
Eye Irritation:  0.751 Respiratory Toxicity:  0.925
Drug-induced Neurotoxicity:  0.785 Ototoxicity:  0.344
Hematotoxicity:  0.347 Drug-induced Nephrotoxicity:  0.535
Genotoxicity:  0.119 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.054 Hek293 Cytotoxicity:  0.277
BCF:   1.814
?
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:   3.298
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.368
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.901
?
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
NPO6447 Kopsia teoi Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[9544563]
NPO15185 Yucca recurvifolia Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8762 Brickellia cylindracea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5289 Calocephalus citreus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11306 Crotalaria medicaginea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12053 Eria alba Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO621 Eria floribunda Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26187 Fritillaria stenanthera Species Liliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6052 Genista pichisermolliana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6447 Kopsia teoi Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12164 Monnieria trifolia n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO10089 Polyalthia barnesii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9852 Polyporus pargamenus Species Polyporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12374 Psychotria st Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7108 Rubus lambertianus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12280 Sidastrum burrerense Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9464 Stevia paniculata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10968 Striga lutea Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12374 Psychotria st Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26177 Macrophomina phaseoli Species Botryosphaeriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11306 Crotalaria medicaginea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2342 Cytisus scoparius Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10089 Polyalthia barnesii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12280 Sidastrum burrerense Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15185 Yucca recurvifolia Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6052 Genista pichisermolliana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO621 Eria floribunda Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8762 Brickellia cylindracea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12053 Eria alba Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9464 Stevia paniculata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5289 Calocephalus citreus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9852 Polyporus pargamenus Species Polyporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12164 Monnieria trifolia n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO25726 Streptomyces echinoruber Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO26187 Fritillaria stenanthera Species Liliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10968 Striga lutea Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7108 Rubus lambertianus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5390 Lupinus pusillus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26595 Cryptocarya amygdalina Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6447 Kopsia teoi 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
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens IC50 = 60000.0 nM PMID[16610785]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 = 331000.0 nM PMID[7798968]
NPT2 Others Unspecified n.a. IC50 = 21000.0 nM PMID[7798968]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition > 95.0 % PMID[6471064]





 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 NPC243635 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 NPC228980
1.0 High Similarity NPC151004

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC243635 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
1.0 High Similarity NPD1822 Approved
1.0 High Similarity NPD1823 Approved
0.8065 Intermediate Similarity NPD1821 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