Succinimidyl 4- (N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) is a heterobifunctional amine-to-sulfhydryl crosslinker, which contains two reactive groups at opposite ends: N-hydroxysuccinimide-ester and maleimide, reactive with amines and thiols respectively. SMCC is often used in bioconjugation to link proteins with other functional entities (fluorescent dyes, tracers, nanoparticles, cytotoxic agents). For example, a targeted anticancer agent – trastuzumab emtansine (antibody-drug conjugate containing an antibody trastuzumab chemically linked to a highly potent drug DM-1) – is prepared using SMCC reagent. In a pharmacokinetics study, the CX-DM1-containing ADCs exhibited stability comparable to that of SMCC-DM1-containing ADCs. SMCC is a classic noncleavable linker that has been employed in Kadcyla. However, SMCC-based conjugates are still limited due to their instability in the circulatory system and hydrophobic properties.