SET and AL amyloidosis: Several small-molecule NSD2 inhibitors havebeen discovered totarget either the SET domain (1, 2, 3) or PWWP1 domain (4, 5) of NSD2(Figure 1).11−15 However, these inhibitors suffer from low activity or inferior selectivity.16−18 While compound KTX-1001, a novel NSD2-SET inhibitor developed byK36 Therapeutics, Inc., was advanced into phase I clinical trialsto treat patients with relapsed and refractory multiple myeloma in2022 (ClinicalTrials.gov identifier: NCT05651932), its structure andpreclinical data have not been disclosed.