ATM-3507 is a protomyosin inhibitor with anticancer activity that inhibits human melanoma and can be used to study ovarian cancer.

Tropomyosin (human melanoma celllines):3.83-6.84 μM

The combination of two troponin inhibitors plus vincristine was completely cytotoxic to CHLA-20 cells. These cell lines differed in the relative expression of Tpm3.1 as well as in the expression of other isoenzymes. All four cell lines showed some degree of synergistic effect as determined by the Chou-Talalay method. This effect was not limited to periwinkle alkaloids, as similar combined efficacy was observed with paclitaxel plus TR100 or ATM-3507 [1]. In determining the IC50 concentrations of 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 [2]: 5.00 ± 0.42 μM) in a neuroblastoma The combination of troponin inhibitors and vincristine was tested in cell lines, and each drug killed less than 50% of neuroblastoma cells when used alone.

The maximum tolerated doses (MTD) of TR100 and ATM-3507 were 60 mg/kg and 150 mg/kg, respectively. The study found that twice-weekly intravenous administration of ATM-3507 also demonstrated combination efficacy, and both combination therapies significantly inhibited tumor growth and prolonged animal survival compared to each monotherapy. Median survival increased from 18 days in mice treated with ATM-3507 to more than 49 days in mice treated with the combination therapy. The effect on body weight was minimal with each therapy or combination of therapies. Drug levels were determined after intravenous administration of 30 mg/kg of ATM-3507 to Balb/c mice (n=3 per time point). Steady-state plasma clearance and volume of distribution of ATM-3507 were observed to be 33.8 mL/min/kg and 7.23 L/kg, respectively [1].The mean half-life of terminal elimination of ATM-3507 was 5.01 hours. The mean AUC0-t in plasma was 14,548 ng/h/mL.