Arimoclomol maleate | BRX-220 | CAS#289893-26-1

MedKoo Cat#: 326988 | Name: Arimoclomol maleate

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Arimoclomol, also known as BRX-220, is a heat shock protein amplifier, and is potentially useful for the treatment of Niemann-Pick disease type C (NP-C). Arimoclomol is believed to function by stimulating a normal cellular protein repair pathway through the activation of molecular chaperones. Arimoclomol could treat a broad range of diseases. Arimoclomol activates the heat shock response. It is believed to act at Hsp70.

Chemical Structure

Arimoclomol maleate

CAS#289893-26-1 (maleate)

Theoretical Analysis

MedKoo Cat#: 326988

Name: Arimoclomol maleate

CAS#: 289893-26-1 (maleate)

Chemical Formula: C18H24ClN3O7

Exact Mass: 429.1303

Molecular Weight: 429.85

Elemental Analysis: C, 50.30; H, 5.63; Cl, 8.25; N, 9.78; O, 26.05

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 195.00	Ready to ship
50mg	USD 320.00	Ready to ship
100mg	USD 550.00	Ready to ship
200mg	USD 950.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 3,250.00	Ready to ship

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Related CAS #

289893-25-0 (free base) 289893-26-1 (maleate) 368860-21-3 (citrate)

Synonym

Arimoclomol maleate; BRX-220; BRX 220; BRX220; BRX-345; BRX 345; BRX345.

IUPAC/Chemical Name

(R,Z)-3-(chloro((2-hydroxy-3-(piperidin-1-yl)propoxy)imino)methyl)pyridine 1-oxide maleate

InChi Key

OHUSJUJCPWMZKR-GARNONDBSA-N

InChi Code

InChI=1S/C14H20ClN3O3.C4H4O4/c15-14(12-5-4-8-18(20)9-12)16-21-11-13(19)10-17-6-2-1-3-7-17;5-3(6)1-2-4(7)8/h4-5,8-9,13,19H,1-3,6-7,10-11H2;1-2H,(H,5,6)(H,7,8)/b16-14-;2-1-/t13-;/m1./s1

SMILES Code

Cl/C(C1=C[N+]([O-])=CC=C1)=N\OC[C@H](O)CN2CCCCC2.O=C(O)/C=C\C(O)=O

Appearance

Solid powder

Purity

>99% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# 289893-25-0 (Arimoclomol) 289893-26-1 (Arimoclomol maleate)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S8S09C04

QC Data

View QC data: current batch, Lot#S8S09C04

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Arimoclomol maleate (BRX-220) is a co-inducer of heat shock proteins (HSP).

In vitro activity:

Arimoclomol is a co-inducer of the heat shock response, which includes the amplification of HSP70 chaperones. Whether arimoclomol amplifies and prolongs the expression of HSP70 encoded by HSPA1A was tested in primary L444P/L444P GD (Gaucher Disease) cells. Doses of arimoclomol of 100–400 μM increased the expression of HSPA1A suggesting a relatively high stress-threshold in the fibroblasts under standard cell culture conditions (Supplementary Fig. 1a). In addition, a time-dependent increase of HSPA1A and HSPA5 was seen by treatment with 400 μM arimoclomol (Supplementary Fig. 1a–b). The folding and ER-to-golgi transition of mutant GCase variants with or without arimoclomol treatment was also investigated. Arimoclomol dose-dependently increased the amount of GCase in primary GD fibroblasts across all tested genotypes, including neuronopathic and non-neuronopathic associated mutations (Fig. 1d–e). Reference: EBioMedicine. 2018 Dec;38:142-153. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306395/

In vivo activity:

The effect of BRX-220, a co-inducer of heat shock proteins, in injury-induced peripheral neuropathy was examined. Following sciatic nerve injury in adult rats and treatment with BRX-220, the following features of the sensory system were studied: (a) expression of calcitonin gene-related peptide (CGRP); (b) binding of isolectin B4 (IB4) in dorsal root ganglia (DRG) and spinal cord; (c) stimulation-evoked release of substance P (SP) in an in vitro spinal cord preparation and (d) nociceptive responses of partially denervated rats. BRX-220 partially reversed axotomy-induced changes in the sensory system. In vehicle-treated rats there was a decrease in IB4 binding and CGRP expression in injured neurones, while in BRX-220-treated rats these markers were better preserved. Thus, 7.0 +/- 0.6% of injured DRG neurones bound IB4 in vehicle-treated rats compared to 14.4 +/- 0.9% in BRX-220-treated animals. Similarly, 4.5 +/- 0.5% of DRG neurones expressed CGRP in the vehicle-treated group, whereas 9.0 +/- 0.3% were positive in the BRX-220-treated group. BRX-220 also partially restored SP release from spinal cord sections to electrical stimulation of primary sensory neurones. Reference: Exp Neurol. 2003 Dec;184(2):636-47. https://www.sciencedirect.com/science/article/abs/pii/S0014488603003431?via%3Dihub

	Solvent	mg/mL	mM
Solubility
	DMSO	250.0	581.60
	Water	100.0	232.64

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 429.85 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Fog CK, Zago P, Malini E, Solanko LM, Peruzzo P, Bornaes C, Magnoni R, Mehmedbasic A, Petersen NHT, Bembi B, Aerts JFMG, Dardis A, Kirkegaard T. The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase. EBioMedicine. 2018 Dec;38:142-153. doi: 10.1016/j.ebiom.2018.11.037. Epub 2018 Nov 27. PMID: 30497978; PMCID: PMC6306395. 2. 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. doi: 10.1016/S0014-4886(03)00343-1. PMID: 14769355. 3. Kürthy M, Mogyorósi T, Nagy K, Kukorelli T, Jednákovits A, Tálosi L, Bíró 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. doi: 10.1111/j.1749-6632.2002.tb04306.x. PMID: 12079878.

In vitro protocol:

In vivo protocol:

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. doi: 10.1016/S0014-4886(03)00343-1. PMID: 14769355. 2. Kürthy M, Mogyorósi T, Nagy K, Kukorelli T, Jednákovits A, Tálosi L, Bíró 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. doi: 10.1111/j.1749-6632.2002.tb04306.x. PMID: 12079878.

1: Sitarska D, Tylki-Szymańska A, Ługowska A. Treatment trials in Niemann-Pick type C disease. Metab Brain Dis. 2021 Dec;36(8):2215-2221. doi: 10.1007/s11011-021-00842-0. Epub 2021 Oct 1. PMID: 34596813; PMCID: PMC8580890. 2: Kürthy M, Mogyorósi T, Nagy K, Kukorelli T, Jednákovits A, Tálosi L, Bíró 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. doi: 10.1111/j.1749-6632.2002.tb04306.x. PMID: 12079878. 3: 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. doi: 10.1016/S0014-4886(03)00343-1. PMID: 14769355. 4: Rakonczay Z Jr, Iványi B, Varga I, Boros I, Jednákovits A, Németh I, Lonovics J, Takács 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. doi: 10.1016/s0891-5849(02)00833-x. PMID: 12057766. 5: Seböková E, Kürthy M, Mogyorosi T, Nagy K, Demcáková 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. doi: 10.1111/j.1749-6632.2002.tb04298.x. PMID: 12079870. 6: Mengel E, Patterson MC, Da Riol RM, Del Toro M, Deodato F, Gautschi M, Grunewald S, Grønborg S, Harmatz P, Héron B, Maier EM, Roubertie A, Santra S, Tylki-Szymanska A, Day S, Andreasen AK, Geist MA, Havnsøe Torp Petersen N, Ingemann L, Hansen T, Blaettler T, Kirkegaard T, Í Dali C. Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomised, placebo-controlled, multinational phase 2/3 trial of a novel treatment. J Inherit Metab Dis. 2021 Nov;44(6):1463-1480. doi: 10.1002/jimd.12428. Epub 2021 Sep 7. PMID: 34418116; PMCID: PMC9293014. 7: McDermott CJ. Clinical trials in amyotrophic lateral sclerosis. Curr Opin Neurol. 2019 Oct;32(5):758-763. doi: 10.1097/WCO.0000000000000731. PMID: 31335338. 8: Dilzer K. Upcoming market catalysts in Q1 2021. Nat Rev Drug Discov. 2021 Jan;20(1):9. doi: 10.1038/d41573-020-00216-8. PMID: 33299128. 9: Kalmar B, Burnstock G, Vrbová 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. doi: 10.1006/exnr.2002.7945. PMID: 12093085. 10: Lilleker JB. Advances in the early diagnosis and therapy of inclusion body myositis. Curr Opin Rheumatol. 2018 Nov;30(6):644-649. doi: 10.1097/BOR.0000000000000537. PMID: 30074510. 11: Rose MR, Jones K, Leong K, Walter MC, Miller J, Dalakas MC, Brassington R, Griggs R. Treatment for inclusion body myositis. Cochrane Database Syst Rev. 2015 Jul 14;7(6):CD001555. doi: 10.1002/14651858.CD001555.pub5. PMID: 35658164; PMCID: PMC9645777. 12: Bremova-Ertl T, Schneider S. Current advancements in therapy for Niemann- Pick disease: progress and pitfalls. Expert Opin Pharmacother. 2023 May 21:1-19. doi: 10.1080/14656566.2023.2215386. Epub ahead of print. PMID: 37211769. 13: Guettsches AK, Meyer N, Zahedi RP, Evangelista T, Muentefering T, Ruck T, Lacene E, Heute C, Gonczarowska-Jorge H, Schoser B, Krause S, Hentschel A, Vorgerd M, Roos A. FYCO1 Increase and Effect of Arimoclomol-Treatment in Human VCP-Pathology. Biomedicines. 2022 Sep 30;10(10):2443. doi: 10.3390/biomedicines10102443. PMID: 36289705; PMCID: PMC9598455. 14: Blasco H, Patin F, Andres CR, Corcia P, Gordon PH. Amyotrophic Lateral Sclerosis, 2016: existing therapies and the ongoing search for neuroprotection. Expert Opin Pharmacother. 2016 Aug;17(12):1669-82. doi: 10.1080/14656566.2016.1202919. Epub 2016 Jul 4. PMID: 27356036. 15: Liščić RM. Molecular basis of ALS and FTD: implications for translational studies. 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