Arimoclomol (
INN; originally codenamed BRX-345, which is a citrate salt formulation of BRX-220) is an experimental drug developed by
CytRx Corporation, a biopharmaceutical company based in
Los Angeles, California. In 2011 the worldwide rights to arimoclomol were bought by Danish biotech company Orphazyme ApS.[1] The
European Medicines Agency (EMA) and
U.S. Food & Drug Administration (FDA) granted orphan drug designation to arimoclomol as a potential treatment for
Niemann-Pick type C in 2014 and 2015 respectively.[2][3]
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 has been shown to extend life in an animal model of ALS[11] and was well tolerated in healthy human volunteers in a
Phase I study. CytRx is currently conducting a Phase II clinical trial.[12]
Arimoclomol also has been shown to be an effective treatment in an animal model of Spinal Bulbar Muscular Atrophy (SBMA, also known as Kennedy's Disease).[13]
Arimoclomol was discovered by Hungarian researchers, as a drug candidate to treat
insulin resistance[14][15] 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 sold to CytRx Corporation, who developed it toward a different direction from 2003.
^Kieran D, Kalmar B, Dick JR, Riddoch-Contreras J, Burnstock G, Greensmith L (April 2004). "Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice". Nat. Med. 10 (4): 402–5.
doi:
10.1038/nm1021.
PMID15034571.
S2CID2311751.
^Kalmar B, Greensmith L, Malcangio M, McMahon SB, Csermely P, Burnstock G (December 2003). "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. 184 (2): 636–47.
doi:
10.1016/S0014-4886(03)00343-1.
PMID14769355.
S2CID5316222.
^Rakonczay Z, Iványi B, Varga I, et al. (June 2002). "Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats". Free Radic. Biol. Med. 32 (12): 1283–92.
doi:
10.1016/S0891-5849(02)00833-X.
PMID12057766.
^Kalmar B, Burnstock G, Vrbová G, Urbanics R, Csermely P, Greensmith L (July 2002). "Upregulation of heat shock proteins rescues motoneurones from axotomy-induced cell death in neonatal rats". Exp. Neurol. 176 (1): 87–97.
doi:
10.1006/exnr.2002.7945.
PMID12093085.
S2CID16071543.
^Kalmar B, Novoselov S, Gray A, Cheetham ME, Margulis B, Greensmith L (October 2008). "Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1 mouse model of ALS". J. Neurochem. 107 (2): 339–50.
doi:
10.1111/j.1471-4159.2008.05595.x.
PMID18673445.
S2CID30026592.