Arimoclomol: Difference between revisions
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== Mechanism of action == |
== Mechanism of action == |
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Arimoclomol is believed to function by stimulating a normal cellular protein repair pathway through the activation of [[chaperone (protein)|molecular chaperone]]s. Since damaged proteins, called aggregates, are thought to play a role in many diseases, CytRx believes that arimoclomol could treat a broad range of diseases. |
Arimoclomol is believed to function by stimulating a normal cellular protein repair pathway through the activation of [[chaperone (protein)|molecular chaperone]]s. Since damaged proteins, called aggregates, are thought to play a role in many diseases, CytRx believes that arimoclomol could treat a broad range of diseases. |
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Arimoclomol activates the [[heat shock protein|heat shock]] response.<ref name="pmid19183864">{{cite journal |author=Kalmar B, Greensmith L |title=Activation of the heat shock response in a primary cellular model of motoneuron neurodegeneration-evidence for neuroprotective and neurotoxic effects |journal=Cell. Mol. Biol. Lett. |volume=14 |issue=2 |pages=319–35 |year=2009 |pmid=19183864 |doi=10.2478/s11658-009-0002-8 |url=http://dx.doi.org/10.2478/s11658-009-0002-8}}</ref> |
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== History == |
== History == |
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Revision as of 23:16, 17 May 2009
{{Drugbox | IUPAC_name = N-{[(2R)-2-hydroxy-3-piperidin-1-ylpropyl]oxy}pyridine-3-carboximidoyl chloride 1-oxide | image = Arimoclomol.svg | CAS_number = 289893-25-0 | ATC_prefix = none | ATC_suffix = | PubChem = 208924 | DrugBank = | C=14|H=20|Cl=1|N=3|O=3 | molecular_weight = 313.78 g/mol | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | pregnancy_AU = | pregnancy_US = | pregnancy_category= | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = Investigational | routes_of_administration = Oral }} Arimoclomol (INN, originally codenamed BRX-220) is an experimental drug developed by CytRx Corporation, a biopharmaceutical company based in Los Angeles, California. The orally administered drug is intended to treat amyotrophic lateral sclerosis (ALS).[1]
Mechanism of action
Arimoclomol is believed to function by stimulating a normal cellular protein repair pathway through the activation of molecular chaperones. Since damaged proteins, called aggregates, are thought to play a role in many diseases, CytRx believes that arimoclomol could treat a broad range of diseases.
Arimoclomol activates the heat shock response.[2]
History
Arimoclomol has been shown to extend life in ALS-affected mice and was well tolerated in healthy human volunteers in a Phase I study. CytRx is currently conducting a Phase II clinical trial at ten centers across the U.S.
Arimoclomol was discovered by Hungarian researchers, as a drug candidate to treat insulin resistance and diabetic complications such as retinopathy, neuropathy and nephropathy. Later, the compound, along with other small molecules, was screened for further development by Hungarian firm Biorex, which was was sold to CytRx Corporation, who developed it toward a different direction from 2003.
References
- ^ Cudkowicz ME, Shefner JM, Simpson E; et al. (2008). "Arimoclomol at dosages up to 300 mg/day is well tolerated and safe in amyotrophic lateral sclerosis". Muscle Nerve. 38 (1): 837–44. doi:10.1002/mus.21059. PMID 18551622.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Kalmar B, Greensmith L (2009). "Activation of the heat shock response in a primary cellular model of motoneuron neurodegeneration-evidence for neuroprotective and neurotoxic effects". Cell. Mol. Biol. Lett. 14 (2): 319–35. doi:10.2478/s11658-009-0002-8. PMID 19183864.
Further reading
- Traynor BJ, Bruijn L, Conwit R, Beal F, O'Neill G, Fagan SC, Cudkowicz ME. Neuroprotective agents for clinical trials in ALS: a systematic assessment. Neurology. 2006 Jul 11;67(1):20-7. Review. PMID 16832072
- Benn SC, Brown RH Jr. Putting the heat on ALS. Nat Med. 2004 Apr;10(4):345-7. PMID 15057226
- Kieran D, Kalmar B, Dick JR, Riddoch-Contreras J, Burnstock G, Greensmith L. Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat Med. 2004 Apr;10(4):402-5. PMID 15034571
- Kalmar B, Greensmith L, Malcangio M, McMahon SB, Csermely P, Burnstock G. The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers of the rat following peripheral nerve injury. Exp Neurol. 2003 Dec;184(2):636-47. PMID 14769355
- Kalmar B, Burnstock G, Vrbova G, Urbanics R, Csermely P, Greensmith L. Upregulation of heat shock proteins rescues motoneurones from axotomy-induced cell death in neonatal rats. Exp Neurol. 2002 Jul;176(1):87-97. PMID 12093085
- Kurthy M, Mogyorosi T, Nagy K, Kukorelli T, Jednakovits A, Talosi L, Biro K. Effect of BRX-220 against peripheral neuropathy and insulin resistance in diabetic rat models. Ann N Y Acad Sci. 2002 Jun;967:482-9. PMID 12079878
- Sebokova E, Kurthy M, Mogyorosi T, Nagy K, Demcakova E, Ukropec J, Koranyi L, Klimes I. Comparison of the extrapancreatic action of BRX-220 and pioglitazone in the high-fat diet-induced insulin resistance. Ann N Y Acad Sci. 2002 Jun;967:424-30. PMID 12079870
- Rakonczay Z Jr, Ivanyi B, Varga I, Boros I, Jednakovits A, Nemeth I, Lonovics J, Takacs T. Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats. Free Radic Biol Med. 2002 Jun 15;32(12):1283-92. PMID 12057766