ATM-3507
ATM-3507 Basic information
- Product Name:
- ATM-3507
- Synonyms:
-
- ATM-3507
- Methanone, [3-[[2,3-dimethyl-1-[3-(4-methyl-1-piperazinyl)propyl]-1H-indol-5-yl]oxy]phenyl][4-[2-(4-fluorophenyl)ethyl]-1-piperazinyl]-
- ATM 3507,ATM3507
- 5-(3-{4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl}phenoxy)-2,3-dimethyl-1-[3-(4-methylpiperazin-1-yl)propyl]-1H-indole
- CAS:
- 1861449-70-8
- MF:
- C37H46FN5O2
- MW:
- 611.79
- Mol File:
- 1861449-70-8.mol
ATM-3507 Chemical Properties
- Boiling point:
- 750.0±60.0 °C(Predicted)
- Density
- 1.19±0.1 g/cm3(Predicted)
- storage temp.
- -10 to -25°C
- solubility
- DMSO: 2mg/mL, clear
- form
- Solid
- pka
- 7.68±0.10(Predicted)
- color
- Light yellow to yellow
ATM-3507 Usage And Synthesis
Uses
ATM-3507 is a potent tropomyosin inhibitor with IC50s from 3.83-6.84 μM in human melanoma cell lines.
Biological Activity
ATM-3507 is a potent anti-tropomyosin agent th at disables Tpm3.1 containing actin filaments. It exhibits potent cytotoxic activity against multiple neuroblastoma cancer cell lines. ATM-3507 sensitizes cancer cells to anti-microtubule agents. ATM-3507 significantly prolonged mitotic arrest induced by anti-microtubule agent vinorelbine.
in vivo
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[1].
References
[1] Currier MA, et al. Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs.Mol Cancer Ther. 2017 Aug;16(8):1555-1565. DOI:10.1158/1535-7163.MCT-16-0873
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