CAS 66635-93-6 R-Ketorolac - Analytical Products / Alfa Chemistry

CAT	AP66635936
CAS	66635-93-6
MDL Number	MFCD00871492
Molecular Weight	255.27
InChI Key	OZWKMVRBQXNZKK-LLVKDONJSA-N

Description	≥95% (HPLC)
Solubility	DMSO: 25 mg/mL, clear
Assay	≥95% (HPLC)
Color	white to beige
Form	powder
Size	5MG, 25MG
Storage Conditions	−20°C

Dual Actions of Ketorolac in Metastatic Ovarian Cancer

Laurie G Hudson, Linda S Cook, Martha M Grimes, Carolyn Y Muller, Sarah F Adams, Angela Wandinger-Ness

Cancers (Basel). 2019 Jul 24;11(8):1049.

PMID: 31344967

Population Pharmacokinetics of Periarticular Ketorolac in Adult Patients Undergoing Total Hip or Total Knee Replacement Surgery

Usha Gurunathan, Suzanne L Parker, Richard Maguire, Dale Ramdath, Manu Bijoor, Steven C Wallis, Jason A Roberts

Anesth Analg. 2019 Sep;129(3):701-708.

PMID: 31425209

Preclinical Enantioselective Pharmacology of (R)- And (S)- Ketorolac

D A Handley, P Cervoni, J E McCray, J R McCullough

J Clin Pharmacol. 1998 Feb;38(2S):25S-35S.

PMID: 9549656

R-Ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis

Yuna Guo, S Ray Kenney, Carolyn Y Muller, Sarah Adams, Teresa Rutledge, Elsa Romero, Cristina Murray-Krezan, Rytis Prekeris, Larry A Sklar, Laurie G Hudson, Angela Wandinger-Ness

Mol Cancer Ther. 2015 Oct;14(10):2215-27.

PMID: 26206334

The R-Enantiomer of Ketorolac Delays Mammary Tumor Development in Mouse Mammary Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) Mice

Amanda S Peretti, Dayna Dominguez, Martha M Grimes, Helen J Hathaway, Eric R Prossnitz, Melanie R Rivera, Angela Wandinger-Ness, Donna F Kusewitt, Laurie G Hudson

Am J Pathol. 2018 Feb;188(2):515-524.

PMID: 29169987

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Case Study

R-Ketorolac Used for the Allosteric Inhibition of Cdc42 and Rac1 GTPase Nucleotide Binding

Guo, Yuna, et al. Molecular cancer therapeutics 14.10 (2015): 2215-2227.

R-ketorolac is used for the selective allosteric inhibition of GTP binding to small GTPases Cdc42 and Rac1-key regulators in cellular signaling pathways. In vitro studies employed a bead-based flow cytometry assay to evaluate the effect of R-ketorolac on fluorescent BODIPY-GTP binding activity. In equilibrium binding assays, R-ketorolac altered both the maximum fluorescence intensity (Bmax) and the apparent dissociation constant (Kd) for GTP binding to Cdc42 and Rac1, indicating a noncompetitive inhibition mechanism.
To assess enantiomeric specificity, dose-response experiments were performed with constant GTP concentrations (Kd ≈ 300 nM). Increasing R-ketorolac concentrations resulted in a dose-dependent decrease in GTP binding, with EC50 values of 18.87 μM for Cdc42 and 23.08 μM for Rac1. Maximal inhibition reached ~20% for both targets. In contrast, S-ketorolac showed negligible or no inhibitory effect under identical conditions.
These results demonstrate that R-ketorolac functions as a selective allosteric inhibitor, disrupting GTPase activity by targeting an allosteric site distinct from the nucleotide binding pocket. This enantiomer-specific action supports the utility of R-ketorolac as a molecular probe or potential therapeutic lead in GTPase-related pathways.
Thus, R-ketorolac is not only pharmacologically distinct from its S-enantiomer but also represents a novel tool for modulating Cdc42 and Rac1 activity through a noncompetitive mechanism.

R-Ketorolac Used for the Treatment of Cancer-Associated Cachexia and Enhances Survival in Tumor-Bearing Mice

Chrysostomou, S. E., Eder, S., Pototschnig, I., Mayer, A. L., Derler, M., Mussbacher, M., ... & Schweiger, M. (2024). Journal of Cachexia, Sarcopenia and Muscle, 15(2), 562-574.

R-ketorolac (RK), the R-enantiomer of a non-steroidal anti-inflammatory drug, is used for the treatment of cancer-associated cachexia (CAC)-a systemic wasting syndrome marked by involuntary loss of skeletal muscle and adipose tissue. In a murine model of CAC, induced via subcutaneous inoculation of C26 or CHX207 tumor cells, RK was administered orally at 2 mg/kg daily following onset of ≥5% body weight loss. Control groups received either phosphate-buffered saline (PBS) or the ghrelin receptor agonist anamorelin
RK-treated mice demonstrated significantly improved survival, with 100% survival at day 10 post-treatment versus 10% and 25% in PBS- and anamorelin-treated cohorts, respectively (P = 0.0009). Moreover, when RK was co-administered with the chemotherapeutic agent cyclophosphamide (Cy), it completely reversed Cy-induced lethality-100% of RK+Cy-treated animals survived 14 days versus only 10% survival in the Cy-only group (P = 0.0001).
Further mechanistic analyses involved muscle histology, qPCR, western blotting, flow cytometry, and COX activity assays. RK treatment attenuated muscle atrophy, reduced systemic inflammation, and showed compatibility with chemotherapy, positioning it as a promising candidate for supportive CAC therapy.
This study highlights the therapeutic potential of R-ketorolac in ameliorating cachexia symptoms and improving overall survival during anticancer treatment.