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Cimlanod (Synonyms: BMS-986231; CXL-1427)

Catalog No.GC39360

Cimlanod (BMS-986231) is a second-generation Nitroxyl (HNO) donor for heart failure.

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Cimlanod Chemical Structure

Cas No.: 1620330-72-4

Size Price Stock Qty
10mg
$237.00
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50mg
$237.00
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100mg
$881.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Background

Cimlanod (BMS-986231) is a second-generation Nitroxyl (HNO) donor for heart failure. Cimlanod (BMS-986231) delivers HNO via pH-dependent chemical breakdown when exposed to the neutral pH environment of the bloodstream. Cimlanod (BMS-986231) possesses positive lusitropic and inotropic as well as vasodilatory effects[1][2].

[1]. Cowart D, et al. A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers. J Clin Pharmacol. 2019 May;59(5):717-730. [2]. Felker GM, et al. Rationale and design for the development of a novel nitroxyl donor in patients with acute heart failure. Eur J Heart Fail. 2019 Aug;21(8):1022-1031.

Chemical Properties

Cas No. 1620330-72-4 SDF
Synonyms BMS-986231; CXL-1427
Canonical SMILES O=S(C1=CC=C(O1)C)(NO)=O
Formula C5H7NO4S M.Wt 177.18
Solubility DMSO: 125 mg/mL (705.50 mM) Storage 4°C, protect from light, stored under nitrogen
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.
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Research Update

Haemodynamic effects of the nitroxyl donor Cimlanod (BMS-986231) in chronic heart failure: a randomized trial

Eur J Heart Fail 2021 Jul;23(7):1147-1155.PMID:33620131DOI:10.1002/ejhf.2138.

Aims: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor Cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF). Methods and results: In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of Cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with Cimlanod (29 ± 9 mL/m2 ; P = 0.03) and NTG (28 ± 8 mL/m2 ; P = 0.02). Transmitral E-wave Doppler velocity on Cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to Cimlanod on these measurements. Blood pressure reduction was similar with Cimlanod and NTG and greater than with placebo. Conclusion: In patients with chronic HFrEF, the haemodynamic effects of Cimlanod and NTG are similar. The effects of Cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of Cimlanod will further define its potential role in the treatment of heart failure.

Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study

JACC Heart Fail 2021 Feb;9(2):146-157.PMID:33248986DOI:10.1016/j.jchf.2020.10.012.

Objectives: The primary objective was to identify well-tolerated doses of Cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (Cimlanod) is an HNO donor being developed for acute heart failure (AHF). Methods: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with Cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of Cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of Cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic). Results: In part I (n = 100), clinically relevant hypotension was more common with Cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for Cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for Cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro-B-type natriuretic peptide and bilirubin decreased during infusion of Cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. Conclusions: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325).

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Average Rating: 5 ★★★★★ (Based on Reviews and 22 reference(s) in Google Scholar.)

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