Description
RSM-932A is a selective inhibitor of choline kinase α (CHOKα; IC
50s = 1 and >50 μM for CHOKα and β, respectively). It induces apoptosis
via CHOP signaling and endoplasmic reticulum (ER) stress in MDA-MB-231, MCF-7, SW620, and H460 cancer cells, but it only induces cell cycle arrest and not apoptosis in NCM460 and MCF-10A normal epithelial cells. RSM-932A inhibits the growth of HT-29 colon cancer cells
in vitro (IC
50 = 1.15 μM) and
in vivo in a mouse xenograft model (ED
50 = 7.5 mg/kg).
Uses
RSM-932A (TCD-717) is a specific ChoKα inhibitor with IC50s of 1 and 33 μM for human recombinant ChoKα and ChoKβ enzymes, respectively. RSM-932A acts as the “first in humans” compound targeting ChoKα. RSM-932A is potent in vitro anti-proliferative and in vivo anti-tumoral activity against human xenografts in mice, showing high efficacy with low toxicity profiles[1][2][3].
in vivo
RSM-932A exhibits a potent in vivo anticancer activity, and lack of toxicity at the effective doses[1].
| Animal Model: | Athymic nu/nu mice, CD1 nude mice, and BALB/c nude (six-week-old) bearing human tumor xenografts (colon adenocarcinoma HT29, non-small cell lung cancer (NSCLC) H-460, breast adenocarcinoma MDA-MB-231)[3] |
| Dosage: | 7.5 mg/kg, 6 mg/kg, 5 mg/kg, 3 mg/kg, 1 mg/kg, 0.3 mg/kg |
| Administration: | Administration routes (intraperitoneal or intravenous), treatment schedule (5 consecutive days, 3 days per week, 2 days per week, 1 day per week) |
| Result: | The LD50 was 10.9 mg/kg in mice. The effective dose used in the in vivo experiments was 7.5 mg/kg. |
References
[1] Juan Carlos Lacal, et al. Preclinical characterization of RSM-932A, a novel anticancer drug targeting the human choline kinase alpha, an enzyme involved in increased lipid metabolism of cancer cells. Mol Cancer Ther. 2015 Jan;14(1):31-9. DOI:
10.1158/1535-7163.MCT-14-0531[2] Ana de la Cueva, et al. Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts. PLoS One. 2013 Jun 10;8(6):e64961. DOI:
10.1371/journal.pone.0064961[3] Tahl Zimmerman, et al. Identification and validation of novel and more effective choline kinase inhibitors against Streptococcus pneumonia. Sci Rep. 2020 Sep 22;10(1):15418. DOI:
10.1038/s41598-020-72165-6[4] Tahl Zimmerman, et al. Antiplasmodial activity and mechanism of action of RSM-932A, a promising synergistic inhibitor of Plasmodium falciparum choline kinase. Antimicrob Agents Chemother. 2013 Dec;57(12):5878-88. DOI:
10.1128/AAC.00920-13
