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Antibody-drug Conjugates & Bioconjugates


scientistData generated from SMARTag-designed ADCs to date demonstrate conjugate stability – even with cleavable linkers – to deliver efficacy with improved tolerability and a wider therapeutic window.


RED-106, a proprietary noncleavable linker with a maytansine payload, is used in a Phase 1 clinical trial (TRPH-222) offering:

  • Stable payload attachment to mAb
  • No bystander effect, reducing off-target toxicities
  • Maintains potency in cells with upregulated P-glycoprotein
  • Can induce immunogenic cell death in target cells
  • Improved tolerability and efficacy as compared to conventional maytansine linkers (e.g., Kadcyla®)
Depiction the chemical structure of RED-106 comprising maytansine payload attached to hydrazino-indol HIPS moiety through a hydrophilic spacer. The latter consists of 4-aminopiperidine with a PEG sidechain attached to the amino group.


Traditional cleavable linkers require one “key” for payload release and can lead to release during circulation, while SMARTag® tandem-cleavage linkers require two “keys” for payload release where tumor cells have both keys. This offers superior stability and reduced toxicity in vivo.

Depiction of a schematic diagram of antibody-drug conjugate consisting of a drawing of an antibody connected to a payload, which is represented by a grey-colored sphere, through a chemical linker. The linker is represented by its chemical structure which consists of indole moiety attached to the antibody, a hydrophilic chemical spacer that is attached to valine-alanine dipeptide, followed by para-aminobenzyl unit which is connected to the payload via carbamate group. The para-aminobenzyl moiety includes glucuronide attached to the benzene ring via a glycoside bond at the ortho-position relative to the dipeptide attachment. All together these elements constitute the tandem-cleavage linker, which requires two enzymatic cleavage events to release the payload. The order of these enzymatic events is shown in the picture by the assigned numerical values - 1 and 2, where the first step is assigned to the cleavage of the glucuronide moiety by the act of glucuronidase enzyme, while the dipeptide is cleaved in the second step by cathepsins. The picture also shows schematically the proposed hindrance effect of the glucuronide unit which prevents the cleavage of the dipeptide group prior to the complete removal of glucuronide in the first step of the process.