Bimoclomol acts as a heat shock protein (HSP) co-inducer by targeting heat shock factor-1 (HSF-1), prolonging its activation (no IC50/Ki/EC50 values specified) [2]
Bimoclomol induces heat shock protein 70 (HSP70) expression in cells, with its target linked to HSF-1-mediated HSP transcriptional regulation (no IC50/Ki/EC50 values specified) [3]

Bimoclomol (40 μM) considerably increases coronary flow (CF) during normoxic perfusion (pre-ischemia). Bimoclomol significantly raised LVDP and CO but lowered LVEDP in ischemia circumstances. Bimoclomol displays a biphasic effect on relaxation rate. Bimoclomol (>10 μM) produces concentration-dependent vasodilation with an EC50 value of 214 μM. Bimoclomol (100 μM) similarly causes vasodilation in response to 20 mM KCl. However, bimoclomol is unable to relax agents precontracted with serotonin, PGF2, or angiotensin II [1]. Bimoclomol does not change the stability of Hsp70 or its mRNA. Bimoclomol promotes Hsp expression via delaying the activation of heat shock transcription factor (HSF-1). The effects of bimoclomol were reduced in cells from mice missing HSF-1. In addition, bimoclomol can bind to HSF-1 and cause extended interaction of HSF-1 with homologous DNA sites [2]. Bimoclomol (0.1, 1, and 10 μM) increased cell survival in rat neonatal cardiomyocytes compared with vehicle-treated cells. Bimoclomol (0.01 to 10 μM) significantly elevated HSP70 levels depending on exposure time. Pretreatment with Bimoclomol for 24 hours can considerably boost the survival rate of cells [3].

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In isolated rat aortic rings (with intact endothelium), bimoclomol (10⁻⁷ to 10⁻⁴ M) had no significant effect on basal tension. However, at concentrations ≥10⁻⁵ M, it slightly inhibited phenylephrine-induced (10⁻⁶ M) contraction: at 10⁻⁴ M, the maximum contraction amplitude was reduced by ~15% [1]
In HeLa cells and human foreskin fibroblasts, bimoclomol (10 μM) prolonged HSF-1 activation. Unlike heat shock (42°C for 15 minutes, HSF-1 activation returned to baseline within 2 hours), bimoclomol maintained HSF-1 in an activated state for >8 hours. This led to increased HSP expression: HSP70 levels were ~3.5-fold higher and HSP90 levels ~2.0-fold higher at 6 hours post-treatment (detected by Western blot) [2]
In primary rat neonatal cardiomyocytes, bimoclomol (1, 5, 10 μM) dose-dependently elevated HSP70: at 10 μM, HSP70 protein levels increased by ~4.2-fold (Western blot). Pretreatment with bimoclomol (10 μM, 24 hours) reduced H₂O₂-induced (200 μM) cell death: cell survival rate increased from 45% (H₂O₂ alone) to 78% (bimoclomol + H₂O₂, MTT assay) [3]

In dogs under anesthesia, bimoclomol (1 and 5 mg/kg) can attenuate ST-segment elevation by 56% and 80%, respectively, due to coronary artery blockage [1].

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In anesthetized male Wistar rats (urethane, 1.2 g/kg ip), intravenous bimoclomol caused dose-dependent mean arterial blood pressure (MABP) decreases: - 0.1 mg/kg: ~5% MABP reduction (not significant); - 1 mg/kg: ~12% MABP reduction (P<0.05) at 10 minutes, recovered to baseline by 30 minutes; - 10 mg/kg: ~25% MABP reduction (P<0.01) at 5 minutes, recovered to 80% of baseline by 60 minutes. Heart rate (HR) and ECG parameters (PR interval, QT interval, QRS duration) remained unchanged at all doses [1]

To assess HSF-1 activation: Cells were treated with bimoclomol (10 μM) or heat shock (42°C, 15 minutes). At 0.5–8 hours post-treatment, nuclear proteins were extracted. Electrophoretic Mobility Shift Assay (EMSA) was performed using a biotin-labeled heat shock element (HSE) probe (specific for activated HSF-1). The HSF-1-HSE complex was separated by non-denaturing PAGE, transferred to a membrane, and visualized by chemiluminescence. Band intensity was quantified to measure HSF-1 activity [2]
To detect HSP70 levels: Rat neonatal cardiomyocytes were treated with bimoclomol (1, 5, 10 μM) for 24 hours. Total proteins were extracted and quantified. Equal amounts (30 μg) were separated by SDS-PAGE, transferred to a nitrocellulose membrane, and incubated with anti-HSP70 primary antibody and HRP-conjugated secondary antibody. Immunoreactive bands were detected by ECL, with β-actin as the internal reference. Band intensity was quantified via image analysis [3]

Isolated rat aortic ring assay: Thoracic aortas from Wistar rats (250–300 g) were cut into 3–4 mm rings, mounted in an organ bath (Krebs-Henseleit solution, 37°C, 95% O₂/5% CO₂), and connected to a force transducer. After 60-minute equilibration (1 g tension), rings were precontracted with phenylephrine (10⁻⁶ M). Bimoclomol was added cumulatively (10⁻⁷ to 10⁻⁴ M), and tension changes were recorded for 30 minutes per concentration [1]
HSF-1 activation and HSP expression assay: HeLa cells/foreskin fibroblasts were seeded (2×10⁵ cells/well, 6-well plate) and cultured to 80% confluence. Cells were treated with bimoclomol (1, 5, 10 μM) or medium (control), or heat-shocked (42°C, 15 minutes). At 0.5–8 hours, cells were harvested for nuclear/total protein extraction (for EMSA/Western blot). Trypan blue exclusion assay confirmed no cytotoxicity at tested concentrations [2]
Cardiomyocyte protection assay: Rat neonatal cardiomyocytes (1–2-day-old rats) were isolated via digestion, purified by differential adhesion, and cultured for 48 hours. Cells were pretreated with bimoclomol (1, 5, 10 μM) for 24 hours, then exposed to H₂O₂ (200 μM) for 6 hours. Cell viability was measured by MTT assay (absorbance at 570 nm). HSP70 levels were detected by Western blot as described in Enzyme Assay [3]

Male Wistar rats (220–280 g) were fasted for 12 hours (water ad libitum). Anesthesia was induced with urethane (1.2 g/kg ip), with supplements (0.1 g/kg ip) as needed. The right carotid artery was cannulated to a pressure transducer for MABP/HR recording. Subcutaneous needle electrodes recorded lead II ECG. After 30-minute stabilization, bimoclomol was administered via tail vein (iv) at 0.1, 1, or 10 mg/kg (6 rats/group). The drug was dissolved in 0.9% NaCl: 1 mg/mL (0.1/1 mg/kg, 0.1/1 mL/kg volume) or 10 mg/mL (10 mg/kg, 1 mL/kg volume). MABP, HR, and ECG were recorded at baseline and 5, 15, 30, 45, 60 minutes post-administration. Rats were euthanized with excess urethane post-experiment [1]

No obvious cytotoxicity (in vitro) or acute adverse reactions (e.g., animal death, abnormal behavior) were observed at tested doses [1][2][3]

[1]. In vivo and in vitro acute cardiovascular effects of bimoclomol. Gen Pharmacol. 2000 May;34(5):363-9.

[2]. Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1. Biochem Biophys Res Commun. 2003 Aug 1;307(3):689-95.

[3]. Bimoclomol elevates heat shock protein 70 and cytoprotects rat neonatal cardiomyocytes. Eur J Pharmacol. 2002 Jan 18;435(1):73-7.

Bimoclomol is a synthetic heat shock protein (HSP) co-inducer that modulates the heat shock response pathway [2][3]
Bimoclomol does not induce HSF-1 synthesis but prolongs its activation, thereby promoting sustained HSP (HSP70, HSP90) expression [2]
The cytoprotective effect of bimoclomol on rat neonatal cardiomyocytes is associated with elevated HSP70, which enhances resistance to H₂O₂-induced oxidative stress [3]
In anesthetized rats, bimoclomol exerts mild, dose-dependent vasodilation (reduced MABP) without altering HR or ECG, suggesting no obvious cardiotoxicity at tested doses [1]

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Bimoclomol is an investigational drug that induces stress proteins and has cytoprotective effects.

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Drug Indication
Investigated for use/treatment in neuropathy (diabetic) and wounds.

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Mechanism of Action
Bimoclomol binds to HSF-1 and induces a prolonged binding of HSF-1 to the respective DNA elements. Since HSF-1 does not bind to DNA in the absence of stress, the bimoclomol-induced extension of HSF-1/DNA interaction may contribute to the chaperone co-induction of bimoclomol observed previously. These findings indicate that bimoclomol may be of value in targeting HSF-1 so as to induce up-regulation of protective Hsp-s in a non-stressful manner and for therapeutic benefit.

C14H20N3O2CL

297.7805

297.124

C, 56.47; H, 6.77; Cl, 11.90; N, 14.11; O, 10.75

130493-03-7

9576891

Light yellow to brown ointment

1.27g/cm3

454ºC at 760mmHg

228.4ºC

0mmHg at 25°C

1.588

1.783

1

5

6

20

309

0

Cl/C(C1=CC=CN=C1)=N\OCC(O)CN2CCCCC2

NMOVJBAGBXIKCG-VKAVYKQESA-N

InChI=1S/C14H20ClN3O2/c15-14(12-5-4-6-16-9-12)17-20-11-13(19)10-18-7-2-1-3-8-18/h4-6,9,13,19H,1-3,7-8,10-11H2/b17-14-

(3Z)-N-(2-hydroxy-3-piperidin-1-ylpropoxy)pyridine-3-carboximidoyl chloride

Bimoclomol; 130493-03-7; BRLP-42; ABT-822; 9IYF14814M; bimoclomolum; (Z)-N-(2-hydroxy-3-(piperidin-1-yl)propoxy)pyridine-3-carbonimidoyl chloride; RefChem:119826;

2934.99.9001

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 (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~335.82 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.40 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 25.0 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.40 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 25.0 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.

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 (Please use freshly prepared in vivo formulations for optimal results.)