RAP-103 is a potent and selective antagonist of the CCL2/CCR2 signaling axis, which plays a central role in monocyte/macrophage recruitment and inflammatory pain pathways. Preclinical studies have shown that RAP-103 inhibits CCR2-mediated chemotaxis with an IC₅₀ in the low nanomolar range (reported values vary, e.g., around 6–10 nM). In animal models, RAP-103 demonstrates significant efficacy in reducing neuropathic pain and inflammatory hyperalgesia, with dose-dependent antinociceptive effects observed in models such as spinal nerve ligation and bone cancer pain. Moreover, RAP-103 has been investigated as a non-opioid alternative or adjunct to morphine, showing synergy in enhancing morphine’s analgesic effect while potentially lowering opioid requirements and tolerance development. RAP-103 is an orally acting version of DAPTA
MedKoo Cat#: 556400
Name: RAP-103
CAS#: 1337998-99-8
Chemical Formula: C25H38N6O11
Exact Mass: 598.2599
Molecular Weight: 598.61
Elemental Analysis: C, 50.16; H, 6.40; N, 14.04; O, 29.40
The following data is based on the product molecular weight 598.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
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2: Pawlik K, Mika J. Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain. Molecules. 2023 Jul 30;28(15):5766. doi: 10.3390/molecules28155766. PMID: 37570736; PMCID: PMC10421203.
3: Bongiovanni AR, Zhao P, Inan S, Wiah S, Shekarabi A, Farkas DJ, Watson MN, Wimmer ME, Ruff MR, Rawls SM. Multi-chemokine receptor antagonist RAP-103 inhibits opioid-derived respiratory depression, reduces opioid reinforcement and physical dependence, and normalizes opioid-induced dysregulation of mesolimbic chemokine receptors in rats. Drug Alcohol Depend. 2022 Sep 1;238:109556. doi: 10.1016/j.drugalcdep.2022.
4: Ruff MR, Inan S, Shi XQ, Meissler JJ, Adler MW, Eisenstein TK, Zhang J. Potentiation of morphine antinociception and inhibition of diabetic neuropathic pain by the multi-chemokine receptor antagonist peptide RAP-103. Life Sci. 2022 Oct 1;306:120788. doi: 10.1016/j.lfs.2022.120788. Epub 2022 Jul 9. PMID: 35817166; PMCID: PMC9398950.
5: Noda M, Tomonaga D, Kitazono K, Yoshioka Y, Liu J, Rousseau JP, Kinkead R, Ruff MR, Pert CB. Neuropathic pain inhibitor, RAP-103, is a potent inhibitor of microglial CCL1/CCR8. Neurochem Int. 2018 Oct;119:184-189. doi: 10.1016/j.neuint.2017.12.005. Epub 2017 Dec 14. PMID: 29248693.
6: Padi SSV, Shi XQ, Zhao YQ, Ruff MR, Baichoo N, Pert CB, Zhang J. Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation. Pain. 2012 Jan;153(1):95-106. doi: 10.1016/j.pain.2011.09.022. Epub 2011 Oct 26. PMID: 22033364.
