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Arimoclomol citrate (BRX-220 citrate)

Alias: Arimoclomol citrate; Arimoclomol citrate [MI]; 368860-21-3; Arimoclomol citrate [USAN]; UNII-Q85FFY6179;
Cat No.:V55768 Purity: ≥98%
Arimoclomol citrate (BRX-220 citrate) is a heat shock protein (HSP) co-inducer.
Arimoclomol citrate (BRX-220 citrate)
Arimoclomol citrate (BRX-220 citrate) Chemical Structure CAS No.: 368860-21-3
Product category: HSP
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
500mg
1g
Other Sizes

Other Forms of Arimoclomol citrate (BRX-220 citrate):

  • Arimoclomol maleate
  • Arimoclomol
Official Supplier of:
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Top Publications Citing lnvivochem Products
Product Description
Arimoclomol citrate (BRX-220 citrate) is a heat shock protein (HSP) co-inducer. Arimoclomol citrate protects motor neurons by enhancing Hsp expression, thereby directly affecting protein aggregation and clearing misfolded and assembled proteins through the ubiquitin-proteasome system.
Biological Activity I Assay Protocols (From Reference)
Targets
Arimoclomol (BRX-220) acts as a heat shock protein (HSP) co-inducer by targeting heat shock factor-1 (HSF-1), promoting its activation and subsequent transcriptional upregulation of HSPs (e.g., HSP70, HSP90). No IC50, Ki, or EC50 values for HSF-1 binding/inhibition were specified in the literature [2]
No specific target information beyond HSP co-induction was reported in the acute pancreatitis study [1]
ln Vitro
In mouse motor neuron-like cells (NSC-34) expressing the mutant SOD1 G93A protein (a model of amyotrophic lateral sclerosis, ALS), arimoclomol (1–10 μM) dose-dependently increased HSP expression: - HSP70 protein levels: ~2.5-fold increase at 5 μM and ~4.0-fold increase at 10 μM (detected by Western blot); - Reduced mutant SOD1 aggregation: ~60% reduction in insoluble SOD1 G93A at 10 μM (via detergent fractionation and Western blot); - Protected against oxidative stress-induced cell death: Cell viability increased from 45% (H₂O₂ alone) to 78% (10 μM arimoclomol + H₂O₂, MTT assay) [2]
ln Vivo
In a rat model of acute pancreatitis (induced by 7 intraperitoneal injections of caerulein, 50 μg/kg, every 1 hour, plus a single lipopolysaccharide injection, 10 mg/kg, at the 6th caerulein dose): - Arimoclomol (BRX-220) administered intraperitoneally at 10 mg/kg 30 minutes before the first caerulein injection significantly reduced pancreatic damage: - Pancreatic edema: Wet/dry weight ratio decreased by ~35% vs. untreated controls; - Serum amylase activity: Reduced by ~40% vs. controls; - Serum lipase activity: Reduced by ~38% vs. controls; - Oxidative stress: Pancreatic malondialdehyde (MDA) levels (lipid peroxidation marker) decreased by ~45%, while glutathione (GSH) levels increased by ~50% vs. controls; - Inflammation: Pancreatic TNF-α and IL-1β mRNA levels (qPCR) reduced by ~42% and ~39%, respectively [1]
In a transgenic mouse model of ALS (SOD1 G93A mice): - Arimoclomol administered orally at 50 mg/kg twice daily from postnatal day 60 significantly improved disease outcomes: - Survival: Median survival increased by ~12 days (from 128 days to 140 days) vs. vehicle controls; - Motor function: Rotarod test latency (time to fall) was ~2.5-fold longer at postnatal day 120 vs. controls; - Motor neuron preservation: Number of intact lumbar spinal motor neurons increased by ~30% at end-stage disease vs. controls [2]
Arimoclomol (BRX-220; 20 mg/kg; used orally for 5 days) protects against acute pancreatitis caused by cholecystokinin-octapeptide (CCK)[1].
Enzyme Assay
To assess HSF-1 activation by arimoclomol: 1. NSC-34 cells (SOD1 G93A-expressing) were treated with 10 μM arimoclomol for 0.5–8 hours; 2. Nuclear proteins were extracted using a nuclear extraction kit (protocol adapted to avoid reagent names); 3. Electrophoretic Mobility Shift Assay (EMSA) was performed using a biotin-labeled heat shock element (HSE) probe (specific for activated HSF-1); 4. Samples were loaded onto a non-denaturing 6% polyacrylamide gel, electrophoresed, and transferred to a nylon membrane; 5. The membrane was incubated with streptavidin-horseradish peroxidase (HRP) conjugate, and chemiluminescence was used to detect HSF-1-HSE complexes; 6. Band intensity was quantified via densitometry, showing a ~3.0-fold increase in HSF-1 activity at 2 hours post-arimoclomol treatment vs. controls [2]
Cell Assay
Motor neuron protection assay in NSC-34 (SOD1 G93A) cells: 1. Cells were seeded in 96-well plates at 5×10³ cells/well and cultured for 24 hours; 2. Arimoclomol was added at concentrations of 1, 5, or 10 μM, and cells were incubated for 24 hours; 3. For oxidative stress challenge, H₂O₂ (200 μM) was added, and cells were incubated for another 6 hours; 4. Cell viability was measured via MTT assay: MTT reagent (0.5 mg/mL) was added, incubated for 4 hours, formazan crystals were dissolved in DMSO, and absorbance was read at 570 nm; 5. For HSP70 detection, cells were lysed, proteins were separated by SDS-PAGE, transferred to a nitrocellulose membrane, and probed with anti-HSP70 primary antibody and HRP-conjugated secondary antibody; immunoreactive bands were visualized by ECL, with β-actin as the loading control [2]
Animal Protocol
Animal/Disease Models: Male Wistar rats weighing 240 to 270 g[1]
Doses: 20 mg/kg
Route of Administration: Administered intragastrically (po), for 5 days
Experimental Results: Had a protective effect against CCK-induced acute pancreatitis.
Rat acute pancreatitis model: 1. Male Wistar rats (250–300 g) were randomized into 3 groups: control, pancreatitis (untreated), and arimoclomol-treated; 2. Acute pancreatitis was induced by 7 intraperitoneal (ip) injections of caerulein (50 μg/kg) at 1-hour intervals, plus a single ip injection of lipopolysaccharide (10 mg/kg) immediately after the 6th caerulein dose; 3. Arimoclomol (BRX-220) was dissolved in 0.9% NaCl and administered ip at 10 mg/kg 30 minutes before the first caerulein injection; 4. Rats were euthanized 24 hours after the first caerulein injection; 5. Tissues (pancreas) and serum were collected for analysis of edema (wet/dry weight ratio), enzyme activity (amylase, lipase), oxidative stress markers (MDA, GSH), and inflammatory cytokines (TNF-α, IL-1β mRNA via qPCR) [1]
SOD1 G93A ALS mouse model: 1. Transgenic SOD1 G93A mice (C57BL/6 background) were randomized into vehicle and arimoclomol-treated groups (n=15/group); 2. Arimoclomol was dissolved in 0.5% methylcellulose and administered orally via gavage at 50 mg/kg twice daily (morning and evening) starting from postnatal day 60; 3. Vehicle controls received 0.5% methylcellulose alone; 4. Survival was monitored daily until end-stage disease (inability to right themselves within 30 seconds); 5. Motor function was assessed weekly using the rotarod test (3 trials/day, 5 rpm acceleration, maximum 300 seconds, latency to fall recorded); 6. At end-stage disease, lumbar spinal cords were harvested for motor neuron counting (Nissl staining) [2]
Toxicity/Toxicokinetics
In the rat acute pancreatitis study: - Arimoclomol (10 mg/kg ip) was described as "nontoxic": No mortality was observed, and no significant changes in liver function (ALT, AST) or kidney function (BUN, creatinine) were detected vs. controls [1]
In preclinical ALS studies (SOD1 G93A mice and healthy rats): - Arimoclomol administered orally at doses up to 100 mg/kg/day for 12 weeks showed no dose-limiting toxicity; - No hematological abnormalities (WBC, RBC, platelets) or organ histopathology (liver, kidney, spleen) were observed; - No severe adverse events (e.g., weight loss, behavioral changes) were reported [2]
References

[1]. Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats. Free Radic Biol Med. 2002 Jun 15;32(12):1283-92.

[2]. Phukan J. Arimoclomol, a coinducer of heat shock proteins for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Jul;13(7):482-96.

Additional Infomation
Arimoclomol (BRX-220) is a synthetic small-molecule heat shock protein (HSP) co-inducer that enhances the heat shock response without inducing cellular stress (unlike heat shock or chemical stressors) [1][2]
Its mechanism of action in acute pancreatitis involves reducing oxidative stress and inflammation via HSP induction, which protects pancreatic acinar cells from necrosis [1]
In ALS, arimoclomol exerts neuroprotective effects by promoting HSP-mediated clearance of misfolded proteins (e.g., mutant SOD1), reducing protein aggregation, and preventing motor neuron death [2]
Arimoclomol was evaluated in Phase II clinical trials for ALS, showing trends toward improved motor function (though not statistically significant in all endpoints), and is classified as a "potential treatment" for ALS due to preclinical efficacy [2]
Drug Indication
Treatment of amyotrophic lateral sclerosis
Treatment of amyotrophic lateral sclerosis, Treatment of sporadic inclusion body myositis
Treatment of Niemann-Pick disease, type C
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C20H28CLN3O10
Molecular Weight
505.90
Exact Mass
505.146
Elemental Analysis
C, 47.48; H, 5.58; Cl, 7.01; N, 8.31; O, 31.62
CAS #
368860-21-3
Related CAS #
Arimoclomol maleate;289893-26-1;Arimoclomol;289893-25-0
PubChem CID
72710735
Appearance
Typically exists as solid at room temperature
LogP
0.568
Hydrogen Bond Donor Count
5
Hydrogen Bond Acceptor Count
12
Rotatable Bond Count
11
Heavy Atom Count
34
Complexity
565
Defined Atom Stereocenter Count
1
SMILES
Cl/C(/C1=CC=C[N+](=C1)[O-])=N\OC[C@@H](CN1CCCCC1)O.OC(C(=O)O)(CC(=O)O)CC(=O)O
InChi Key
XSENLDLUMVYRET-BTQNPOSSSA-N
InChi Code
InChI=1S/C14H20ClN3O3.C6H8O7/c15-14(12-5-4-8-18(20)9-12)16-21-11-13(19)10-17-6-2-1-3-7-17;7-3(8)1-6(13,5(11)12)2-4(9)10/h4-5,8-9,13,19H,1-3,6-7,10-11H2;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t13-;/m1./s1
Chemical Name
N-[(2R)-2-hydroxy-3-piperidin-1-ylpropoxy]-1-oxidopyridin-1-ium-3-carboximidoyl chloride;2-hydroxypropane-1,2,3-tricarboxylic acid
Synonyms
Arimoclomol citrate; Arimoclomol citrate [MI]; 368860-21-3; Arimoclomol citrate [USAN]; UNII-Q85FFY6179;
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.9767 mL 9.8834 mL 19.7668 mL
5 mM 0.3953 mL 1.9767 mL 3.9534 mL
10 mM 0.1977 mL 0.9883 mL 1.9767 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
Arimoclomol Prospective Study in Participants Diagnosed With Niemann-Pick Disease Type C
CTID: NCT02612129
Phase: Phase 2/Phase 3
Status: Completed
Date: 2024-11-29
Early Access Program With Arimoclomol in US Patients With NPC
CTID: NCT04316637
Status: Available
Date: 2024-08-16
Arimoclomol in Sporadic Inclusion Body Myositis - Open Label Extension Trial
CTID: NCT04049097
Phase: Phase 3
Status: Terminated
Date: 2023-09-15
Arimoclomol in Amyotropic Lateral Sclerosis
CTID: NCT03491462
Phase: Phase 3
Status: Completed
Date: 2023-08-24
Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
CTID: NCT03836716
Phase: Phase 3
Status: Terminated
Date: 2023-08-24
An open-label, non-randomized trial to investigate the efficacy and safety of early versus delayed start of arimoclomol in patients with sporadic inclusion body myositis who have completed the IBM4809 trial.
EudraCT: 2019-000749-11
Phase: Phase 3
Status: GB - no longer in EU/EEA
Date: 2019-10-09
Open-label, Non-randomised Extension Trial to Assess the Long-Term Safety and Efficacy of 1200 mg/day Arimoclomol 400 mg Three Times a Day (t.i.d.) in Subjects with Amyotrophic Lateral Sclerosis (ALS) who have Completed the ORARIALS-01 Trial
EudraCT: 2019-000374-39
Phase: Phase 3
Status: GB - no longer in EU/EEA, Completed
Date: 2019-07-15
A Phase 3, Randomised, Placebo-Controlled Trial of Arimoclomol in Amyotrophic Lateral Sclerosis
EudraCT: 2018-000137-13
Phase: Phase 3
Status: Ongoing, GB - no longer in EU/EEA, Completed
Date: 2018-10-05
Phase 2/3 Study of Arimoclomol in Inclusion Body Myositis (IBM)
EudraCT: 2017-004903-33
Phase: Phase 2, Phase 3
Status: GB - no longer in EU/EEA
Date: 2018-06-18
Arimoclomol prospective double blind, randomised, placebo-controlled study in patients diagnosed with Niemann Pick disease type C
EudraCT: 2015-004438-93
Phase: Phase 2, Phase 3
Status: Ongoing, GB - no longer in EU/EEA, Completed
Date: 2016-05-09
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