Repositioning Candidate Details
| Candidate ID: | R0972 |
| Source ID: | DB06283 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Ziconotide |
| Synonyms: | Ziconotide |
| Molecular Formula: | C102H172N36O32S7 |
| SMILES: | [H][C@]12CSSC[C@]3([H])NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CSSC[C@]([H])(NC(=O)[C@]([H])(CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC1=O)C(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC3=O)C(=O)N[C@@]([H])([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N2 |
| Structure: |
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| DrugBank Description: | Ziconotide (also known as SNX-111) is a neurotoxic peptide derived from the cone snail _Conus magus_ comprising 25 amino acids with three disulphide bonds. Other such peptides, collectively termed conotoxins, exist, and some have shown efficacy in binding specific subsets of calcium channels; ziconotide is used in part because it can be synthesized without loss of proper bond formation or structural elements. Ziconotide is used to manage severe chronic pain refractory to other methods, through its ability to inhibit N-type calcium channels involved in nociceptive signalling. Ziconotide was granted FDA approval on December 28, 2004 for marketing by TerSera therapeutics LLC. under the name Prialt. To date, ziconotide is the only calcium channel blocking peptide approved for use by the FDA. |
| CAS Number: | 107452-89-1 |
| Molecular Weight: | 2639.14 |
| DrugBank Indication: | Ziconotide is indicated for the management of severe chronic pain in patients refractory to other treatments, and for whom intrathecal therapy is warranted. |
| DrugBank Pharmacology: | Ziconotide inhibits N-type calcium channels involved in nociceptive signalling, primarily in the dorsal horn of the spinal cord. Although binding is reversible, careful dosing is required to ensure therapeutic effects while minimizing adverse effects, and ziconotide has been described as possessing a narrow therapeutic window. Patients taking ziconontide may experience cognitive and neuropsychiatric symptoms, reduced levels of consciousness, and elevated serum creatine kinase levels. In addition, ziconotide may increase the risk of infection, including serious cases of meningitis. Patients who withdraw from opiates for ziconotide initiation are advised to taper off the dose. |
| DrugBank MoA: | Nociceptive pain signalling is a complex processing pathway involving peripheral nociceptors, primary afferent nerve fibres, and downstream CNS neurons located in the spinal cord. Voltage-gated calcium channels (VGCCs) are important regulatory components of neural signalling and include the N-type (Cav2.2) heteromultimeric high-voltage type calcium channels. Chronic pain conditions, including inflammatory and neuropathic pain, often involve the aberrant upregulation of VGCC activity through various cellular mechanisms, which can lead to allodynia and hyperalgesia. Specifically, N-type channel activation in lightly myelinated Aδ- and C-fibres is known to mediate the release of neurotransmitters substance P (SP), calcitonin gene-related peptide (CGRP), and glutamate, which influence downstream neural activation and pain perception. In addition, SP and CGRP induce inflammation, potentially exacerbating pre-existing inflammatory chronic pain. Ziconotide belongs to the ω-conotoxin class of neurotoxic peptides derived from the cone snail _Conus magus_ which are capable of inhibiting N-type VGCCs. Although the exact mechanism is yet to be elucidated, it is thought that ω-conotoxins function through direct occlusion of the ion pore to prevent calcium translocation across the membrane. Additional studies involving expression of chimeric subunits and molecular modelling suggest that insertion of the ziconotide Met<sup>12</sup> residue into a hydrophobic pocket formed by Ile<sup>300</sup>, Phe<sup>302</sup>, and Leu<sup>305</sup> of Cav2.2 increases binding and may be associated with toxic adverse effects. |
| Targets: | Voltage-dependent N-type calcium channel subunit alpha-1B inhibitor; Voltage-dependent P/Q-type calcium channel subunit alpha-1A inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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