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Blaugrund E, Gueta R, Zernov A, et al. Mode of Action of RZL-012, a New Fat-Reducing Molecule. Dermatol Surg. 2021;47(12):1601-1605doi: 10.1097/DSS.0000000000003245.
Blaugrund, E., Gueta, R., Zernov, A., & Bloomenfeld, A. (2021). Mode of Action of RZL-012, a New Fat-Reducing Molecule. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 47(12), 1601-1605. https://doi.org/10.1097/DSS.0000000000003245
Blaugrund, Eran, et al. "Mode of Action of RZL-012, a New Fat-Reducing Molecule." Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] vol. 47,12 (2021): 1601-1605. doi: https://doi.org/10.1097/DSS.0000000000003245
Blaugrund E, Gueta R, Zernov A, Bloomenfeld A. Mode of Action of RZL-012, a New Fat-Reducing Molecule. Dermatol Surg. 2021 Dec 01;47(12):1601-1605. doi: 10.1097/DSS.0000000000003245. PMID: 34537791; PMCID: PMC8612913.
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Dermatol Surg. 2021 Dec 01;47(12):1601-1605. doi: 10.1097/DSS.0000000000003245.

Mode of Action of RZL-012, a New Fat-Reducing Molecule.

Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]

Eran Blaugrund, Racheli Gueta, Anton Zernov, Alon Bloomenfeld

Affiliations

  1. Raziel Therapeutics Ltd., Rehovot, Israel.
  2. Faculty of Biotechnology & Food Engineering, Israel Institute of Technology, Technion, Haifa, Israel.

PMID: 34537791 PMCID: PMC8612913 DOI: 10.1097/DSS.0000000000003245

Abstract

BACKGROUND: RZL-012 (5-[3,6-dibromo-9H-carbazol-9-yl]-N,N,N-trimethylpentan-1-aminium chloride) is a novel investigational drug injected subcutaneously into fat tissues in patients with fat-related disorders (Dercum disease) or subjects seeking aesthetic changes.

OBJECTIVE: Preclinical studies were undertaken to understand RZL-012's mechanism of action.

MATERIALS AND METHODS: The effects of RZL-012 were tested in vitro by measuring adipocyte cell killing, membrane integrity, cytosolic calcium, and mitochondrial membrane potential (MMP). In vivo studies in pigs evaluated RZL-012's adipocyte killing effect and measured pig fat thickness in the injected areas.

RESULTS: RZL-012 triggered adipocyte cell killing with IC50 values ranging from 25 to 106 μM. RZL-012 demonstrated initial effects on membrane integrity and calcium levels with delayed alterations in MMP. Incubation of RZL-012 with nanoghosts increased membrane permeability, culminating in full membrane destruction. Analysis of injected areas in pigs revealed liponecrosis 24 hours after dosing followed by an inflammatory response and formation of fibrotic tissue. Three months after dosing, an 18% reduction in mean fat thickness was observed in RZL-012 treated pigs.

CONCLUSION: RZL-012 destroys adipocytes by directly disrupting cell membrane integrity. Replacement of dead fat tissue by fibrotic tissue enables healing and causes contraction of the injected area. These effects are translated into significant reduction in fat tissue volume.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society for Dermatologic Surgery, Inc.

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