Natural Product: NPC279833

Natural Product IDNPC279833
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Lycopsamine
IUPAC Name [(7R,8R)-7-hydroxy-5,6,7,8-tetrahydro-3H-pyrrolizin-1-yl]methyl (2R)-2-hydroxy-2-[(1R)-1-hydroxyethyl]-3-methylbutanoate
Synonyms Lycopsamine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL450265
PubChem CID 44584035
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 SFVVQRJOGUKCEG-BPGGGUHBSA-N
Standard InCHI InChI=1S/C15H25NO5/c1-9(2)15(20,10(3)17)14(19)21-8-11-4-6-16-7-5-12(18)13(11)16/h4,9-10,12-13,17-18,20H,5-8H2,1-3H3/t10-,12-,13-,15-/m1/s1
SMILES CC(C)[C@@]([C@@H](C)O)(C(=O)OCC1=CCN2CC[C@H]([C@@H]12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   299.17 Volume:   300.558
?
Van der Waals volume.
Dense:   0.995 LogP:   0.601
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.75
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.977
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   10.0
TPSA:   90.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.476 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.347 Fsp3:   0.8
MCE-18:   37.926
?
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:   0.245 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.045
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.009
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.01 Promiscuous compounds:   0.169

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.432 MDCK Permeability:   -4.988
Pgp-inhibitor:   0.069 Pgp-substrate:   0.246
PAMPA:   0.509
?
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):   0.008
20% Bioavailability (F20%):   0.467 30% Bioavailability (F30%):   0.736
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.976
Plasma Protein Binding (PPB):   50.899% Volume Distribution (VD):   0.152
Fu: 44.033%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.027
BSEP inhibitor:   0.946

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.011
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   0.043 CYP3A4-substrate:   0.626
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.454
HLM stability:   0.183
?
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):  6.305 Half-life (T1/2):  3.19

ADMET: Toxicity

hERG Blockers:  0.047 hERG Blockers (10um):  0.211
Human Hepatotoxicity (H-HT):  0.906 Drug-induced Liver Injury (DILI):  0.119
AMES Toxicity:  0.401 Rat Oral Acute Toxicity:  0.315
Maximum Recommended Daily Dose:  0.622 Skin Sensitization:  0.967
Carcinogencity:  0.959 Eye Corrosion:  0.0
Eye Irritation:  0.276 Respiratory Toxicity:  0.32
Drug-induced Neurotoxicity:  0.111 Ototoxicity:  0.65
Hematotoxicity:  0.155 Drug-induced Nephrotoxicity:  0.365
Genotoxicity:  0.955 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.033 Hek293 Cytotoxicity:  0.308
BCF:   0.29
?
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:   2.992
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.499
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.581
?
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
NPO19080 Borago officinalis Species Boraginaceae Eukaryota n.a. n.a. n.a. PMID[38797382]
NPO26180 Heliotropium megalanthum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. PMID[9834169]
NPO26180 Heliotropium megalanthum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10937 Symphytum x uplandicum Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7288 Heliotropium steudneri Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19408 Eupatorium compositifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21824 Lycopus lucidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24601 Rumex dentatus Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Fruit Essent. Oil n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Seed Essent. Oil n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Seed Oil n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota n.a. n.a. Database[FooDB]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10937 Symphytum x uplandicum Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7288 Heliotropium steudneri Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21824 Lycopus lucidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19408 Eupatorium compositifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24601 Rumex dentatus Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7288 Heliotropium steudneri Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21824 Lycopus lucidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24601 Rumex dentatus Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19080 Borago officinalis Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10937 Symphytum x uplandicum Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19408 Eupatorium compositifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24601 Rumex dentatus Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21824 Lycopus lucidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21824 Lycopus lucidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21824 Lycopus lucidus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24601 Rumex dentatus Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19408 Eupatorium compositifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26180 Heliotropium megalanthum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19080 Borago officinalis Species Boraginaceae 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
NPT776 Organism Spodoptera littoralis Spodoptera littoralis Activity = 61.08 % PMID[9834169]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis EC50 = 31.62 microg/cm2 PMID[9834169]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis Activity = 21.19 mg PMID[9834169]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis Activity = 3.32 mg PMID[9834169]
NPT1275 Organism Leptinotarsa decemlineata Leptinotarsa decemlineata Activity = 27.53 % PMID[9834169]
NPT1275 Organism Leptinotarsa decemlineata Leptinotarsa decemlineata Activity = 68.4 % PMID[9834169]
NPT1275 Organism Leptinotarsa decemlineata Leptinotarsa decemlineata EC50 = 25.97 microg/cm2 PMID[9834169]
NPT1275 Organism Leptinotarsa decemlineata Leptinotarsa decemlineata Activity = 12.0 % PMID[9834169]

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 NPC279833 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 NPC173690
1.0 High Similarity NPC80439
0.7647 Intermediate Similarity NPC64168
0.7451 Intermediate Similarity NPC6271
0.6964 Remote Similarity NPC609380
0.5273 Remote Similarity NPC52533

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC279833 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