RW-93

RW-93
Clinical data
Drug class	Sirtuin 2 (SIRT2) inhibitor
Chemical and physical data
Formula	C23H22BrN7O3S2
Molar mass	588.50 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(Nc1ccc(cc1Br)OCc1cnc(s1)NC(=O)CSc1nc(C)cc(C)n1)c1cnn(C)c1;
	InChI InChI=InChI=1S/C23H22BrN7O3S2/c1-13-6-14(2)28-23(27-13)35-12-20(32)30-22-25-9-17(36-22)11-34-16-4-5-19(18(24)7-16)29-21(33)15-8-26-31(3)10-15/h4-10H,11-12H2,1-3H3,(H,29,33)(H,25,30,32); Key:LTSQUIAHBBIGDD-UHFFFAOYSA-N;

RW-93 is a drug which acts as a potent and selective sirtuin 2 (SIRT2) inhibitor. It inhibits SIRT2 with an IC₅₀ of 15.5 nM, and is highly selective over SIRT1, SIRT3 and SIRT5, however its activity has not been reported at SIRT4, SIRT6 or SIRT7. It represents a further development of FM358, which resulted from a lead-structure-based hybridization concept derived from SirReal2 and 24a. It was developed to assist with research into the role of SIRT2 in degenerative diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis.^[1]^[2]

References

^ Wirawan R, Frei M, Heider A, Papenkordt N, Friedrich F, Wein T, et al. (November 2025). "Tailored SirReal-type inhibitors enhance SIRT2 inhibition through ligand stabilization and disruption of NAD⁺ co-factor binding". RSC Medicinal Chemistry. 16 (11): 5419–5440. doi:10.1039/d5md00144g. PMC 12412615. PMID 40919320.
^ Frei M, Wirawan R, Wein T, Bracher F (October 2025). "Lead Structure-Based Hybridization Strategy Reveals Major Potency Enhancement of SirReal-Type Sirt2 Inhibitors". International Journal of Molecular Sciences. 26 (20): 9855. doi:10.3390/ijms26209855. PMC 12563821. PMID 41155149.

[1] Wirawan R, Frei M, Heider A, Papenkordt N, Friedrich F, Wein T, et al. (November 2025). "Tailored SirReal-type inhibitors enhance SIRT2 inhibition through ligand stabilization and disruption of NAD⁺ co-factor binding". RSC Medicinal Chemistry. 16 (11): 5419–5440. doi:10.1039/d5md00144g. PMC 12412615. PMID 40919320.

[2] Frei M, Wirawan R, Wein T, Bracher F (October 2025). "Lead Structure-Based Hybridization Strategy Reveals Major Potency Enhancement of SirReal-Type Sirt2 Inhibitors". International Journal of Molecular Sciences. 26 (20): 9855. doi:10.3390/ijms26209855. PMC 12563821. PMID 41155149.

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