| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Arimoclomol, formerly 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 thought to work by inducing molecular chaperones to activate a regular cellular protein repair pathway. Many diseases could be treated with rimoclomol. It is arimoclomol that initiates the HPR. It is thought to function at Hsp70.
| Targets |
HSP; 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 Vivo |
Arimoclomolmaleate (BRX-220; side wall; 5d; 20 mg/kg) guards against acute pancreatitis brought on by cholecystokinin octapeptide (CCK) [1].
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] 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] |
| 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, body weight 240 to 270g [1]
Doses: 20 mg/kg Route of Administration: intragastric (po) (po)administration for 5 days Experimental Results: Protective effect on 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 | |
| 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] |
| Molecular Formula |
C18H24CLN3O7
|
|---|---|
| Molecular Weight |
429.85206
|
| Exact Mass |
429.13
|
| Elemental Analysis |
C, 50.30; H, 5.63; Cl, 8.25; N, 9.78; O, 26.05
|
| CAS # |
289893-26-1
|
| Related CAS # |
Arimoclomol;289893-25-0;Arimoclomol citrate;368860-21-3
|
| PubChem CID |
72941795
|
| Appearance |
White to off-white solid powder
|
| LogP |
1.528
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
29
|
| Complexity |
456
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
Cl/C(C(C=CC=1)=CN1=O)=N\OC[C@H](O)CN2CCCCC2.OC(/C=C\C(O)=O)=O
|
| 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
|
| Chemical Name |
Z)-but-2-enedioic acid;(3Z)-N-[(2R)-2-hydroxy-3-piperidin-1-ylpropoxy]-1-oxidopyridin-1-ium-3-carboximidoyl chloride
|
| Synonyms |
Arimoclomol maleate; BRX220; BRX-220; Arimoclomol maleate; UNII-18D1V854HG; 18D1V854HG; 3-Pyridinecarboximidoyl chloride, N-((2R)-2-hydroxy-3-(1-piperidinyl)propoxy)-, 1-oxide, (2Z)-2-butenedioate (1:1); BRX 220; BRX-345; BRX345; BRX 345
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~250 mg/mL (~581.6 mM)
H2O: ~100 mg/mL (~232.6 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.84 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.84 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (232.64 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3264 mL | 11.6320 mL | 23.2639 mL | |
| 5 mM | 0.4653 mL | 2.3264 mL | 4.6528 mL | |
| 10 mM | 0.2326 mL | 1.1632 mL | 2.3264 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.
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA