Slaframine
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Basic Info
| Common Name | Slaframine(F05015) |
| 2D Structure | |
| Description | Slaframine is a mycotoxin produced by the fungus Rizoctonia leguminicola. It is a parasympathomimetic compound and causes increased exocrine function, especially salivation. Along with swainsonine, the other biologially active compound of R. leguminicola, it is known to cause a condition called "slobbers syndrome" in livestock that has ingested contaminated feed. (A3091, A3092) |
| FRCD ID | F05015 |
| CAS Number | 20084-93-9 |
| PubChem CID | 88363 |
| Formula | C10H18N2O2 |
| IUPAC Name | [(1S,6S,8aS)-6-amino-1,2,3,5,6,7,8,8a-octahydroindolizin-1-yl] acetate |
| InChI Key | YYIUHLPAZILPSG-GUBZILKMSA-N |
| InChI | InChI=1S/C10H18N2O2/c1-7(13)14-10-4-5-12-6-8(11)2-3-9(10)12/h8-10H,2-6,11H2,1H3/t8-,9-,10-/m0/s1 |
| Canonical SMILES | CC(=O)OC1CCN2C1CCC(C2)N |
| Isomeric SMILES | CC(=O)O[C@H]1CCN2[C@H]1CC[C@@H](C2)N |
| Synonyms |
Slaframine
UNII-51H2386GWI
(1S,6S,8aS)-1-Acetoxy-6-aminooctahydroindolizine
51H2386GWI
20084-93-9
[(1S,6S,8aS)-6-amino-1,2,3,5,6,7,8,8a-octahydroindolizin-1-yl] acetate
AC1L3FKI
AC1Q5X5J
SCHEMBL1097317
ZINC22595743
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Indolizidines |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Indolizidines |
| Alternative Parents | |
| Molecular Framework | Aliphatic heteropolycyclic compounds |
| Substituents | Indolizidine - 3-aminopiperidine - Piperidine - N-alkylpyrrolidine - Pyrrolidine - Amino acid or derivatives - Carboxylic acid ester - Tertiary amine - Tertiary aliphatic amine - Monocarboxylic acid or derivatives - Carboxylic acid derivative - Azacycle - Organic oxide - Primary amine - Organopnictogen compound - Organooxygen compound - Organonitrogen compound - Primary aliphatic amine - Organic oxygen compound - Amine - Carbonyl group - Organic nitrogen compound - Hydrocarbon derivative - Aliphatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as indolizidines. These are polycyclic compounds containing an indolizidine, which is a bicyclic heterocycle containing a saturated six-member ring fused to a saturated five-member ring, one of the bridging atoms being nitrogen. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 198.266 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Complexity | 232 |
| Monoisotopic Mass | 198.137 |
| Exact Mass | 198.137 |
| XLogP | 0 |
| Formal Charge | 0 |
| Heavy Atom Count | 14 |
| Defined Atom Stereocenter Count | 3 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9451 |
| Human Intestinal Absorption | HIA+ | 0.9880 |
| Caco-2 Permeability | Caco2+ | 0.5312 |
| P-glycoprotein Substrate | Substrate | 0.7182 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.6207 |
| Non-inhibitor | 0.8967 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.5548 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.8320 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8830 |
| CYP450 2D6 Substrate | Non-substrate | 0.5757 |
| CYP450 3A4 Substrate | Substrate | 0.5341 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8356 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9093 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.6822 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8863 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9821 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9441 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.6605 |
| Non-inhibitor | 0.8352 | |
| AMES Toxicity | Non AMES toxic | 0.6618 |
| Carcinogens | Non-carcinogens | 0.9566 |
| Fish Toxicity | Low FHMT | 0.7594 |
| Tetrahymena Pyriformis Toxicity | Low TPT | 0.7964 |
| Honey Bee Toxicity | Low HBT | 0.6650 |
| Biodegradation | Not ready biodegradable | 0.9733 |
| Acute Oral Toxicity | III | 0.5924 |
| Carcinogenicity (Three-class) | Non-required | 0.6054 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.4845 | LogS |
| Caco-2 Permeability | 0.8380 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.5526 | LD50, mol/kg |
| Fish Toxicity | 2.1502 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.3525 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Mycotoxicoses of ruminants and horses. | J Vet Diagn Invest | 2013 Nov | 24091682 |
| Mycotoxins. | Vet Clin North Am Equine Pract | 2001 Dec | 11780286 |
| New, sensitive high-performance liquid chromatography method for the determination of slaframine in plasma and milk. | J Chromatogr A | 1998 Jul 31 | 9718714 |
| Tropical pasture hay utilization with slaframine and cottonseed meal: ruminal characteristics and digesta passage in wethers. | J Anim Sci | 1993 Jun | 8392051 |
| The indolizidine alkaloids, slaframine and swainsonine: contaminants in animal forages. | Annu Rev Nutr | 1985 | 3927948 |
| Slaframine (Rhizoctonia leguminicola) intoxication in horses. | J Am Vet Med Assoc | 1982 Sep 15 | 7141956 |
| Salivary syndrome in horses: identification of slaframine in red clover hay. | Appl Environ Microbiol | 1981 Dec | 7316513 |
Targets
- General Function:
- Phosphatidylinositol phospholipase c activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM1
- Uniprot ID:
- P11229
- Molecular Weight:
- 51420.375 Da
- Mechanism of Action:
- Slaframine is a parasympathomimetic compound and causes increased secretion by salivary glands, pancreas, and other exocrine and endocrine glands. This is due to its activity as a cholingergic agonist. Slaframine has a high affinity for muscarinic receptors, especially in the gastrointestinal tract, and it stimulates these to produce its parasympathomimetic effects.
References
- Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
- General Function:
- G-protein coupled acetylcholine receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
- Gene Name:
- CHRM2
- Uniprot ID:
- P08172
- Molecular Weight:
- 51714.605 Da
- Mechanism of Action:
- Slaframine is a parasympathomimetic compound and causes increased secretion by salivary glands, pancreas, and other exocrine and endocrine glands. This is due to its activity as a cholingergic agonist. Slaframine has a high affinity for muscarinic receptors, especially in the gastrointestinal tract, and it stimulates these to produce its parasympathomimetic effects.
References
- Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
- General Function:
- Phosphatidylinositol phospholipase c activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM5
- Uniprot ID:
- P08912
- Molecular Weight:
- 60073.205 Da
- Mechanism of Action:
- Slaframine is a parasympathomimetic compound and causes increased secretion by salivary glands, pancreas, and other exocrine and endocrine glands. This is due to its activity as a cholingergic agonist. Slaframine has a high affinity for muscarinic receptors, especially in the gastrointestinal tract, and it stimulates these to produce its parasympathomimetic effects.
References
- Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
- General Function:
- Receptor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
- Gene Name:
- CHRM3
- Uniprot ID:
- P20309
- Molecular Weight:
- 66127.445 Da
- Mechanism of Action:
- Slaframine is a parasympathomimetic compound and causes increased secretion by salivary glands, pancreas, and other exocrine and endocrine glands. This is due to its activity as a cholingergic agonist. Slaframine has a high affinity for muscarinic receptors, especially in the gastrointestinal tract, and it stimulates these to produce its parasympathomimetic effects.
References
- Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
- General Function:
- Guanyl-nucleotide exchange factor activity
- Specific Function:
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
- Gene Name:
- CHRM4
- Uniprot ID:
- P08173
- Molecular Weight:
- 53048.65 Da
- Mechanism of Action:
- Slaframine is a parasympathomimetic compound and causes increased secretion by salivary glands, pancreas, and other exocrine and endocrine glands. This is due to its activity as a cholingergic agonist. Slaframine has a high affinity for muscarinic receptors, especially in the gastrointestinal tract, and it stimulates these to produce its parasympathomimetic effects.
References
- Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]