Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development

Bryan Oronsky; Xiaoning Guo; Xiaohui Wang; Pedro Cabrales; David Sher; Lou Cannizzo; Bob Wardle; Nacer Abrouk; Michelle Lybeck; Scott Caroen; Arnold Oronsky; Tony R. Reid

doi:10.1021/acs.jmedchem.1c00599

Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development

Bryan Oronsky, Xiaoning Guo, Xiaohui Wang, Pedro Cabrales, David Sher, Lou Cannizzo, Bob Wardle, Nacer Abrouk, Michelle Lybeck, Scott Caroen, Arnold Oronsky, Tony R. Reid

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

After extensive screening of aerospace compounds in an effort to source a novel anticancer agent, RRx-001, a first-in-class dinitroazetidine small molecule, was selected for advancement into preclinical and clinical development. RRx-001 is a minimally toxic small molecule with a distinct chemical structure and mechanism of action. The paradox of RRx-001 is that it mediates both antitumor cytotoxicity and normal tissue protection. The question of exactly how RRx-001 does this, and by means of what mechanism(s), depending on the route of delivery, intravenous or intratumoral, are explored. RRx-001 is currently in phase 2 and 3 clinical trials for the treatment of multiple solid tumor malignancies and as a supportive care drug.

Original language	English (US)
Pages (from-to)	7261-7271
Number of pages	11
Journal	Journal of Medicinal Chemistry
Volume	64
Issue number	11
DOIs	https://doi.org/10.1021/acs.jmedchem.1c00599
State	Published - Jun 10 2021

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/acs.jmedchem.1c00599

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Oronsky, B., Guo, X., Wang, X., Cabrales, P., Sher, D., Cannizzo, L., Wardle, B., Abrouk, N., Lybeck, M., Caroen, S., Oronsky, A., & Reid, T. R. (2021). Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development. Journal of Medicinal Chemistry, 64(11), 7261-7271. https://doi.org/10.1021/acs.jmedchem.1c00599

Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development. / Oronsky, Bryan; Guo, Xiaoning; Wang, Xiaohui et al.
In: Journal of Medicinal Chemistry, Vol. 64, No. 11, 10.06.2021, p. 7261-7271.

Research output: Contribution to journal › Article › peer-review

Oronsky, B, Guo, X, Wang, X, Cabrales, P, Sher, D, Cannizzo, L, Wardle, B, Abrouk, N, Lybeck, M, Caroen, S, Oronsky, A & Reid, TR 2021, 'Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development', Journal of Medicinal Chemistry, vol. 64, no. 11, pp. 7261-7271. https://doi.org/10.1021/acs.jmedchem.1c00599

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abstract = "After extensive screening of aerospace compounds in an effort to source a novel anticancer agent, RRx-001, a first-in-class dinitroazetidine small molecule, was selected for advancement into preclinical and clinical development. RRx-001 is a minimally toxic small molecule with a distinct chemical structure and mechanism of action. The paradox of RRx-001 is that it mediates both antitumor cytotoxicity and normal tissue protection. The question of exactly how RRx-001 does this, and by means of what mechanism(s), depending on the route of delivery, intravenous or intratumoral, are explored. RRx-001 is currently in phase 2 and 3 clinical trials for the treatment of multiple solid tumor malignancies and as a supportive care drug.",

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AU - Cabrales, Pedro

AU - Sher, David

AU - Cannizzo, Lou

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AU - Abrouk, Nacer

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Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development

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