1A-116

1A-116, a potent Rac1 inhibitor, is specific for W56 residues, can prevent EGF-induced Rac1 activation and block Rac1-P-Rex1 interaction. 1A-116 can induce apoptosis and inhibit cell proliferation, migration and cycle progression in a concentration-dependent manner. 1A-116 also demonstrates a high antimetastatic activity in vivo^[1][2][3]. IC50 & Target: IC50: 4 µM (F3II); 21 µM (MDA-MB-231)^[1].
Rac1^[1]
Apoptosis^[2] In Vitro: 1A-116 (48 h) inhibits F3II and MDA-MB-231 cells proliferation in a concentration-dependent manner with IC₅₀s of 4 µM and 21 µM, respectively^[1].
1A-116 (1, 10 µM; 12 h) dramatically impaires Rac1 activation, and reduces Rac1-GTP intracellular levels in a concentration-dependent manner in F3II cells^[1].
1A-116 (50, 100 µM; 12 h) blocks Rac1-P-Rex1 interaction^[1].
1A-116 (20 µM; 5 h intervals over 25 h) inhibits LN229 cells proliferation in a circadian manner^[2].
1A-116 (10 µM; 16 h) significantly reduces cell migration at 10 HPS which exhibits temporal dependence. (HPS: After the serum shock, the elapsed time (in hours) is recorded as the hours post-synchronization (HPS))^[2].
1A-116 (20, 50 µM; 6 h) induces cells apoptosis and in a circadian-dependent manner^[2].
1A-116 (100 nM) decreases the thickness of the epidermal layers of Vav2 and Rac1-mediated hyperplasia, but not the PAK1-mediated one, which exhibits the activity of inhibiting Rac1 at the GEF-Rac1 level^[3]. In Vivo: 1A-116 (3 mg/kg; i.v.; once a day for 21 days) demonstrates a high antimetastatic activity with about 60% formation reduction of total metastatic lung colonies in vivo and shows no apparent toxicity^[1].
1A-116 (20 mg/kg; i.p.; once a day, 73 days for ZT12, 68 days for ZT3) increases survival time when treated at ZT12 compare to ZT3 in tumor-bearing mice. (ZT: Zeitgeber time 12 (ZT12) defined as the time of lights off (local time 7 p.m.) and ZT0 defined as lights on (local time 7 a.m.))^[2].
1A-116 shows good oral availability^[3].