AqT®-SN38

SN38 is an inhibitor of topoisomerase I that blocks DNA replication and transcription. On April 7, 2021, the FDA approved sacituzumab govitecan (Trodelvy, Immunomedics, Inc.)—an ADC that consists of SN-38 linked with a humanized anti-TROP-2 IgG antibody—for patients with metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies. TROP-2, a cell-surface glycoprotein, is expressed in over 90% of TNBCs. Unlike highly toxic payloads such as DM1 or MMAE, ADCs using chemotherapeutic agents often require higher drug loading to achieve efficacy. However, SN38 is a highly hydrophobic, and traditional linkers can cuase aggregation and precipitation. The super-hydrophilic, water-soluble, and charge neutral AqT® linker greatly enhances SN38's solubility by forming extensive hydrogen bonds with water, preventing SN38 stacking and protecting the antibody from enzymatic degradation. This result in a high loaded, stable ADC with minimal aggregation. Preliminary in vitro data shows that SN38 with AqT linker often shows much toxic effect on the target with similar loading.

The AqT-SN38 Acid drug asset is currently available for partner evaluation using surface amine labeling chemistry with a releasable ester bond. Click CM81301 for more information.

For other types of AqT-SN38 of labeling chemistries and release mechanisms, please contact us.

AqT®-MMAE

Among ADC payloads, monomethyl auristatin E (MMAE) with a valine-citruline p-aminobenzylcarbamate (VC-PAB) linker is by far the most widely used in the clinical applications. MMAE inhibits cell disvisiion by blocking the polymerization of tubulin. The VC-PAB linker remains stable in extracellular fluid but is cleaved by cathepsin B once inside the tumor cell, thereby activating the antimitotic mechanism. Although an excellent clinically approved linker, VC-PAB introduces significant hydrophobicity to the MMAE molecules, make it impossible to achieve high drug-to-antibody ratios (DARs). 

The Mc-AqT-VC-PAB-MMAE drug asset is currently available for partner evaluation using reduced-thiol chemistry with a releasable VC-PAB linker. Click CM81303 for more information. This drug asset enables the efficient loading of up to eight drug molecules per antibody.

For other types of AqT-MMAE of labeling chemistries and release mechanisms, please contact us.

AqT®-MMAF

MMAF (monomethyl auristatin F) is a new antimitotic auristatin derivative with a charged C-terminal phenylalanine residue. 

The Mc-AqT-VC-PAB-MMAF drug asset is currently available for customer evaluation using reduced-thiol chemistry with a releasable VC-PAB linker. Click CM81306 for more information. This drug asset enables the efficient loading of up to eight drug molecules per antibody.

For other types of AqT-MMAF of labeling chemistries and release mechanisms, please contact us.

AqT®-Calicheamicin

Calicheamicin is one of the most hydrophobic drugs that one can work with. 

The Mc-AqT-Calicheamicin drug asset is currently available for partner evaluation using reduced-thiol chemistry with a releasable linker. Click CM81307 for more information. This drug asset enables the efficient loading of up to four to six drug molecules per antibody easily without significant precipitations.

AqT®-Exatecan

The Mc-AqT-VC-PAB-Exatecan drug asset is currently available for partner evaluation using reduced-thiol chemistry with a releasable VC-PAB linker. Click CM81314 for more information. This drug asset enables the efficient loading of up to eight drug molecules per antibody easily without significant precipitations.

AqT®-Venetoclax

The Mc-AqT-Venetoclax drug asset is currently available for partner evaluation using reduced-thiol chemistry with stable linker. Click CM81309 for more information. This drug asset enables the efficient loading of up to six to eight drug molecules per antibody easily without significant precipitations.

AqT®-UM171

The Mc-AqT-VC-PAB-UM171 drug asset is currently available for partner evaluation using reduced-thiol chemistry with a releasable VC-PAB linker. Click CM81310 for more information. This drug asset enables the efficient loading of up to four to six drug molecules per antibody easily without significant precipitations.