alk-2-in-2

ALK2-IN-2 is a potent and selective inhibitor of activin receptor-like kinase 2 (ALK2) with an IC50 of 9 nM, demonstrating 700-fold higher inhibition of ALK2 compared to ALK3.

ALK2-IN-4 succinate is a potent and effective inhibitor of ALK2 (ActRI), providing significant promise for therapeutic uses [ActR-1].

TGFβRI-IN-2 is a selective, potent and orally active inhibitor of (Activin-Like Kinase 5) ALK 5(pIC50 and pEC50 values of 7.6 and 6.63, respectively).

PROTACALK degrader-1 (compound B1) is a PROTACs-based ALK degrader with a DC50 of 26 nM in H3122 EML4-ALK. It is utilized in creating PROTACALK degrader-2, which boasts excellent bioavailability.

PROTACALK degrader-2 (B1-PEG) is a PROTAC-based ALK degrader with a DC50 of 45 nM in H3122 EML4-ALK DC50 (GSH+). Through PEGylation, PROTACALK degrader-2 can self-assemble into micelles in water, releasing its active form in tumor-specific high-GSH environments.

PROTACEML4-ALK Degrader-2 (Pro-BA) is a selective and orally active EML4-ALK PROTAC degrader without a linker, demonstrating a DC50 of 74 nM and a T1/2 of 8 hours in H1322 cells. It relies on the GID4 and proteasome pathways to facilitate the ubiquitination of target proteins, leading to apoptosis. PROTACEML4-ALK Degrader-2 is applicable in cancer research.

ALK degrader 2 is an orally active ALK degrader that reduces EML4-ALK protein levels (DC50= 8 nM) and nucleophosmin (NPM)-ALK protein levels (DC50= 102 nM). It facilitates ALK degradation through the Hsp70 chaperone system and the ubiquitin-proteasome pathway. In H3122 cells, ALK degrader 2 causes significant cell cycle arrest at the S phase and induces apoptosis. Additionally, it demonstrates antitumor activity in mice with H3122 xenograft tumors. ALK degrader 2 is a useful compound in researching non-small cell lung cancer (NSCLC).

ALK5-IN-25 (compound EX-02) is a potent ALK-5 inhibitor (IC50<10 nM) that also inhibits ALK-2 and can be used in cancer research.

ALK5-IN-27 (Compound EX-04) is a potent inhibitor of ALK-5 (IC50 ≤ 10 nM) and also inhibits ALK-2.

ALK/EGFR-IN-2 is a potent dual inhibitor targeting ALK and EGFR, promoting apoptosis and G0/G1 cell cycle arrest in cancer cells. It effectively suppresses proliferation in H1975, PC9, and Baf3-EML4-ALK cancer cell lines, with IC50s of 0.0034, 0.0065, and 0.0018 μM, respectively [1].

Zilurgisertib fumarate (INB-000928 fumarate, NBU-928 fumarate), a selective ALK-2 inhibitor, is in development for the treatment of ectopic ossification and progressive fibrodysplasia ossificans.