1A-116

Research use only, not for human use.

1A-116 is a specific Rac1 inhibitor.

1A-116 is a specific Rac1 inhibitor.(In Vitro):The presence of 1A-116 reverts the PAK1 phosphorylation induced by 4-hydroxytamoxifen (Tam) and also effectively reverts Rac1-PAK1-mediated estrogen receptor (ER) phosphorylation at Ser305. 1A-116 shows lesser effect on MCF7::pcDNA.3 cells than on MCF7::C1199 cells, and it also shows a significant increase in antiproliferative activity on F3II cells, reveal an IC50 value of 4 μM. 1A-116 treatment decreases phospho-PAK1 levels in a time-dependent manner. Which also dramatically impairs Rac1 activation at low micromolar range (1 μM). (In Vivo):A significant antitumor activity is obtained for macronodules (more than 1 mm in diameter) by treatment with 1A-116 in this highly aggressive breast cancer model.Daily treatment of mice with compound 1A-116 at 3mg/kg body weight/day reduces about 60% the formation of total metastatic lung colonies. The treatment with 1A-116 reduces the total lung weight compare to the control group, leading to a total weight similar to the average pulmonary weight of Balb/c mice.

Cell Proliferation Assay Cell Line:MDA-MB-231, F3II, LN229 cells Concentration:20 μM Incubation Time:48 h; 5 h intervals over 25 h.Result:Inhibited cell proliferation in a concentration-dependent and circadian manner.Cell Viability AssayCell Line:Ker-CT human keratinocytes cells with oncogenic Vav2/Rac1 F28L/PAK1 Tyrosine 423 Concentration:100 nM Incubation Time:Result:Inhibited Rac1 activity at the GEF-Rac1 level.Cell Migration Assay Cell Line:LN229 cells Concentration:10 μM Incubation Time:16 h Result:Reduced cell migration at 10 HPS which exhibited temporal dependence.Apoptosis Analysis Cell Line:LN229 cells Concentration:20, 50 μM Incubation Time:6 h Result:Induced cells apoptosis and in a circadian-dependent manner.Western Blot Analysis Cell Line:F3II cells Concentration:1, 10 μM Incubation Time:12 h Result:Blocked Rac1-P-Rex1 interaction.Reduced Rac1-GTP intracellular levels in a concentration-dependent manner.

Animal Model:Female BALB/c inbred mice (8 to 10-week-old; average 20 g)Dosage:3 mg/kg Administration:Intravenous injection; once a day for 21 days.Result:Demonstrated a high antimetastatic activity.Animal Model:Male NIH Swiss foxN1(?/?) nude mice (2-month-old; GBM model).Dosage:20 mg/kg Administration:Intraperitoneal injection (at ZT3, ZT12); once a day, 73 days for ZT12, 68 days for ZT3.Result:Increased survival time when treated at ZT12 compared to ZT3 in tumor-bearing mice.

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Cell Cycle/DNA Damage

Rho

Human Endogenous Metabolite

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1430208-73-3

307.32

C16H16F3N3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (325.40 mM)

Cc1cc(C)cc(NC(=N)Nc2ccccc2C(F)(F)F)c1

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(-20℃)

With Ice Pack

≥ 2 years