TML-2Cl 

TML-2Cl is a dichloro-modified trimethyl lock adapter for antibody-drug conjugates and payload releaser.TML-2Cl undergoes 1,6-elimination followed by rapid self-cyclization to facilitate release of the payload Exatecan after cathepsin B cleavage of the associated linker.TML-2Cl exhibits high stability when conjugated to a drug and high intrinsic hydrophobicity.TML-2Cl can be used for the research of gastric carcinoma^[1].

TML-2Cl (1 h) enables efficient Exatecan release via 1,6-elimination and self-cyclization following reduction in a cell-free system^[1].
TML-2Cl-containing linker-payloads with Val-Ala cleavage sites (LP03, L10081, L10082) (4-20 h) exhibit higher cathepsin B-mediated Exatecan release efficiency than those with GGFG cleavage sites; L10081 and L10082 achieve near-complete payload release within 4 h in vitro^[1].
TML-2Cl-containing ADCs Her2-L10081 and Her2-L10082 (72 h) exhibit potent, HER2-dependent antiproliferative activity in vitro, with IC₅₀ values ranging from 108.09 nM to 287.40 nM in HER2-positive cell lines and weak activity in HER2-negative MDA-MB-231 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ADCs incorporating TML-2Cl (3 mg/kg; i.v.; single dose) significantly suppress tumor growth in NCI-N87 xenograft mice, with no observed acute organ toxicity or body weight loss^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

422.31

C₂₀H₂₁Cl₂N₃O₃

OC(CC(C)(C)C1=C(C)C(Cl)=C(C)C(Cl)=C1OCC2=CC=C(N=[N+]=[N-])C=C2)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Xuzhuo Li, et al. Trimethyl Lock-2Cl (TML-2Cl): A self-cyclizing adapter for molecular release in antibody-drug conjugates. Eur J Med Chem. 2026 Mar 15:306:118640.  [Content Brief]