ATTECs

LC3-mHTT-IN-AN2 (5,7-Dihydroxy-4-phenylcoumarin) is found in the plant Passiflora serratodigitata with the antibacterial activity.

LC3-mHTT-IN-AN1 is a mHTT-LC3 linker compound that interacts with both mutant huntingtin protein (mHTT) and LC3B. LC3-mHTT-IN-AN1 targeted mHTT to autophagosomes reduces the levels of mHTT in an allele-selective manner in cultured Huntington disease (HD) mouse neurons.

LC3B recruiter 2 (34R) is an LC3B recruiting agent incorporated into the autophagy-lysosome pathway degradation system (ATTEC, Autophagy-Tethering Compounds), with a direct binding affinity for LC3B. It connects via a linker to the CDK9 inhibitor SNS-032, creating an ATTEC capable of targeting and degrading the CDK9 and Cyclin T1 complex, while also inhibiting them. Consequently, LC3B recruiter 2 exerts its function through an LC3B-dependent autophagy-lysosome pathway, interfering with the cancer cell cycle progression, thereby demonstrating antitumor activity.

PDEδ autophagic degrader 1 (compound 12c) is an autophagosome-tethering compound (ATTEC) and a potent autophagic degrader of PDEδ. This compound effectively reduces PDEδ protein levels through lysosome-mediated autophagy without affecting PDEδ mRNA expression. Additionally, PDEδ autophagic degrader 1 inhibits the growth of KRAS mutant pancreatic cancer cells.

LLC355 is a discoidin domain receptor 1 (DDR1) ATTEC degrader. It efficiently degrades DDR1 protein, with a DC50 value of 150.8 nM in non-small cell lung cancer NCI-H23 cells. LLC355 induces DDR1 degradation via lysosome-mediated autophagy and effectively inhibits the tumorigenicity, migration, and invasion of cancer cells.

MRL828 is a compound that combines a Tau pathology-binding ligand with a guanine group modified by ATTEC technology, allowing it to selectively target aggregated tau proteins for clearance via the autophagy-lysosome pathway (ALP). MRL828 reduces intracellular Tau aggregates and facilitates the secretion of Tau.

PCSK9 autophagic degrader 2 (W6) is an autophagosome-targeting agent for PCSK9, with a DC50 value of 20.6 nM. It exhibits effects comparable to anti-atherosclerotic treatments and has a binding constant (KD) with LC3B of 2.5 μM.

MC-ND-18 is an ATTEC degrader that facilitates the degradation of NLRP3 via autophagy, exhibiting a DC50 of 125.5 nM in THP-1 cells. It is composed of an NLRP3 ligand, a linker, and an LC3 ligand.