ATM-3507

Research use only, not for human use.

ATM-3507 (ATM3507) is a small molecule inhibitor of Tpm3.1 tropomyosin isoform, disrupts Tpm3.1-containing microfilaments in SK-N-SH cells at 5 uM.

ATM-3507 (ATM3507) is a small molecule inhibitor of Tpm3.1 tropomyosin isoform, disrupts Tpm3.1-containing microfilaments in SK-N-SH cells at 5 uM; shows cancer cell cytotoxicity comparable with the first-in-class tool compound TR100, also shows a strong synergistic effect when TR100 or ATM-3507 were combined with antimicrotubule agents in both in vitro and in vivo neuroblastoma models.

The cell lines differ in their relative expression of Tpm3.1 as well as in the expression of other isoforms. After determing the IC50 concentrations for TR100 and ATM-3507 (CHLA-20: 4.99±0.45 μM, CHP-134: 3.83±0.67 μM, CHLA-90: 6.84±2.37 μM, SK-N-BE(2): 5.00±0.42 μM) in each of the neuroblastoma cell lines, combinations of tropomyosin inhibitors plus Vincristine are tested at levels of each drug alone that kill less than 50% of the neuroblastoma cells. The combinations of both tropomyosin inhibitors plus Vincristine are completely cytotoxic in CHLA-20 cells. All 4 cell lines show some degree of synergy as determined by the Chou–Talalay method. The effect is not limited to the vinca alkaloids as a similar combination efficacy using paclitaxel plus TR100 or ATM-3507.

The maximal tolerance dose (MTD) for TR100 and ATM-3507 is 60 and 150 mg/kg, respectively. It is found that a significant inhibition of tumor growth and prolongation of animal survival using either combination compared with each monotherapy. The median survival of mice increased from 18 days for mice treated with ATM-3507 to more than 49 days for mice treated with the combination. It is also found that twice weekly intravenous administration of ATM-3507 also show combination efficacy. The impact of each treatment or the combination on body weight is minimal. Drug levels are measured following the intravenous administration of ATM-3507 at 30 mg/kg in Balb/c mice (n=3 per time point). The mean half-life of ATM-3507 is 5.01 hrs for the terminal elimination phase. The mean AUC0-t in the plasma is 14,548 ng/h/mL. The Cmax of ATM-3507 is 5,758 ng/mL and the the t1/2 is 5.01 h. The observed plasma clearance and volume of distribution at steady state of ATM-3507 is 33.8 mL/min/kg and 7.23 L/kg, respectively.

ATM3507 | ATM 3507

Cytoskeleton/Cell Adhesion Molecules

Microtubule/Tubulin

Microtubule/Tubulin

Cancer

——

1861449-70-8

611.806

C37H46FN5O2

>98% (HPLC)

In Vitro:?DMSO : 33.33 mg/mL (54.48 mM)

O=C(C1=CC=CC(OC2=CC3=C(N(CCCN4CCN(C)CC4)C(C)=C3C)C=C2)=C1)N5CCN(CCC6=CC=C(F)C=C6)CC5

(3-((2,3-dimethyl-1-(3-(4-methylpiperazin-1-yl)propyl)-1H-indol-5-yl)oxy)phenyl)(4-(4-fluorophenethyl)piperazin-1-yl)methanone

(-20℃)

With Ice Pack

≥ 2 years