SA-8 (drug)

SA-8 (drug)
Clinical data
Drug class	SHP2 targeting AUTAC
Identifiers
ChemSpider	133321345;
Chemical and physical data
Formula	C46H51Br2Cl2IN10O7
Molar mass	1213.59 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C\1Nc2ccc(I)cc2/C/1=C/c1cc(Br)c(OCC(=O)NCCOCCOCCOCCOCCn2nnc(c2)CNC2(C)CCN(CC2)c2nc(N)c(nc2)c2cccc(Cl)c2Cl)c(Br)c1;
	InChI InChI=InChI=1S/C46H51Br2Cl2IN10O7/c1-46(7-10-60(11-8-46)39-26-54-42(44(52)57-39)32-3-2-4-37(49)41(32)50)55-25-31-27-61(59-58-31)12-14-65-16-18-67-20-19-66-17-15-64-13-9-53-40(62)28-68-43-35(47)22-29(23-36(43)48)21-34-33-24-30(51)5-6-38(33)56-45(34)63/h2-6,21-24,26-27,55H,7-20,25,28H2,1H3,(H2,52,57)(H,53,62)(H,56,63)/b34-21-; Key:LPVCESFXKLMSMS-ZXSNDDASSA-N;

SA-8 is a drug that acts as an AUTAC selective for the protein tyrosine phosphatase enzyme SHP-2 (PTPN11), acting to target this protein for destruction by cell maintenance enzymes. This is a similar approach to older PROTAC drugs which target unwanted proteins for destruction by proteasomes, but AUTACs instead target unwanted proteins for destruction by autophagosomes, which allows for targeting of proteins in cells and tissue types where PROTACs would not be effective.^[1] SA-8 was derived from an older drug SHP099 which acts as an SHP-2 inhibitor. It has been investigated for treatment of various forms of cancer, and while it is unlikely to be developed for clinical use in humans itself, SA-8 represents an important proof of concept of the AUTAC approach which is likely to lead to the development of related compounds for medical use.^[2]

References

^ Takahashi D, Moriyama J, Nakamura T, Miki E, Takahashi E, Sato A, et al. (December 2019). "AUTACs: Cargo-Specific Degraders Using Selective Autophagy". Molecular Cell. 76 (5): 797–810.e10. doi:10.1016/j.molcel.2019.09.009. PMID 31606272.
^ Song H, Zou X, Liang J, Huang H, Liu Y, Zhang Y, et al. (November 2025). "Discovery of SA-8 as a potent SHP2-AUTAC degrader in cancer therapy". European Journal of Medicinal Chemistry. 297 117918. doi:10.1016/j.ejmech.2025.117918. PMID 40609222.

[1] Takahashi D, Moriyama J, Nakamura T, Miki E, Takahashi E, Sato A, et al. (December 2019). "AUTACs: Cargo-Specific Degraders Using Selective Autophagy". Molecular Cell. 76 (5): 797–810.e10. doi:10.1016/j.molcel.2019.09.009. PMID 31606272.

[2] Song H, Zou X, Liang J, Huang H, Liu Y, Zhang Y, et al. (November 2025). "Discovery of SA-8 as a potent SHP2-AUTAC degrader in cancer therapy". European Journal of Medicinal Chemistry. 297 117918. doi:10.1016/j.ejmech.2025.117918. PMID 40609222.

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