Arimoclomol is an experimental drug compound developed by CytRx Corporation, a biopharmaceutical company based in
Los Angeles, California. The orally administered drug is intended to treat amyotrophic lateral sclerosis(ALS).
Mechanism of Action
The small molecule drug candidate 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.
Arimolclomol has been shown to extend life in ALS-affected mice and was well tolerated in healthy human volunteers in a recently completed 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 with other small molecules were synthetised and screened for further development, by Biorex (a firm seatled in Hungary) was sold to CytRx Corporation, who developed it toward a different, but very promising direction, from 2003.
Hungarian institutional code of Arimoclomol was: BRX-220.
Publication date of the patent: 2001-12-03Publication number: SK11582001Inventor: KURTHY MARIA (HU); BIRO KATALIN (HU); NAGY KAROLY (HU); UROGDI LASZLO (HU); CSAKAI ZITA (HU); SZILBEREKY JENO (HU); MOGYOROSI TAMAS (HU); TOROK MAGDOLNA (HU); KOMAROMI ANDRAS (HU); MARVANYOS EDE (HU); BARABAS MIHALY (HU); KARDOS MIHALYNE (HU); NAGY ZOLTAN (HU); KORANYI LASZLO (HU); NAGY MELINDA (HU)Applicant: BIOREX KUTATO FEJLESZTOE KFT (HU)Classification: - international: A61P3/10; C07D213/89; A61P3/00; C07D213/00; (IPC1-7): C07D213/89; A61K31/44; A61P3/10- European: C07D213/89BApplication number: SK20010001158 20000224Priority number(s): HU19990000475 19990226; WO2000HU00015 20000224Abstract of corresponding document: WO0050403The invention relates to N- [2-hydroxy-3-(1-piperidinyl)-propoxy] -pyridine-1-oxide-3-carboximidoyl chloride, its stereoisomers and the acid addition salts thereof, pharmaceutical compositions containing the same, the use of these compounds in the treatment of pathological insulin resistance, and for the treatment of pathological conditions associated therewith, by simultaneous treatment and prevention of diabetes-induced chronic complications, especially retinopathy, neuropathy and nephropathy and/or with simultaneous increasing pathologically decreased peripheral neuroregeneration caused by diabetes and methods of treatment.
List of publications:Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed"K"ey word: Arimoclomol in PubMe"d:"1: 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 [PubMed - indexed for MEDLINE]
2: Benn SC, Brown RH Jr. Putting the heat on ALS. Nat Med. 2004 Apr;10(4):345-7. No abstract available. MID: 15057226 [PubMed - indexed for MEDLINE]
3: 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. Epub 2004 Mar 21. PMID 15034571 [PubMed - indexed for MEDLINE]
"Key word: BRX-220 in PubMed:"1: 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 [PubMed - indexed for MEDLINE]
2: Kalmar B, Burnstock G, Vrbova G, Urbanics R, Csermely P, Greensmith L. R 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 [PubMed - indexed for MEDLINE]
3: 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 [PubMed - indexed for MEDLINE]
4: 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 [PubMed - indexed for MEDLINE]
5: 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 [PubMed - indexed for MEDLINE]
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