Remodelin hydrobromide

• CAT Number: I002086
• CAS Number: 1622921-15-6
• Molecular Formula: C15H15BrN4S
• Molecular Weight: 363.28
• Purity: ≥95%
• Synonyms: 4-[2-(2-cyclopentylidenehydrazinyl)-1,3-thiazol-4-yl]benzonitrile;hydrobromide
• InChI: InChI=1S/C15H14N4S.BrH/c16-9-11-5-7-12(8-6-11)14-10-20-15(17-14)19-18-13-3-1-2-4-13;/h5-8,10H,1-4H2,(H,17,19);1H
• InChIKey: XNWBCMSPDCSWSD-UHFFFAOYSA-N
• SMILES: C1CCC(=NNC2=NC(=CS2)C3=CC=C(C=C3)C#N)C1.Br

Remodelin hydrobromide is an orally active and selective inhibitor of acetyltransferase NAT10. Remodelin hydrobromide inhibits NAT10 activitity and slows DNA replication and suppresses growth of prostate cancer cells. Remodelin hydrobromide inhibits the growth of prostate cancer and hepatocellular carcinoma in xenograft model. Remodelin hydrobromide enhances the healthspan in hutchinson-gilford progeria syndrome (HGPS) mouse model[1][2][3][4].
Remodelin hydrobromide (10-40 μΜ, 1-7 days) inhibits NAT10 activity and cell proliferation with a dose-dependent manner in both AR-positive and AR-negative prostate cancer cells[2].
Remodelin hydrobromide (20 μΜ, 24 hours) inhibits NAT10 and slows DNA replication in prostate cancer cells[2].
Remodelin hydrobromide (1 μΜ, 7 days) decreases nuclear shape defects and increase genomic stability in LmnaG609G/G609G fibroblasts[3].
Remodelin hydrobromide (2 or 20 mg/kg, i.p., once every two days for 4 weeks) significantly reduces AR-negative prostate cancer tumor growth in tumor xenograft nude mice model[2].
Remodelin hydrobromide (100 mg/kg, p.o.) inhibits NAT10 and significantly enhances the healthspan in aLmnaG609G/G609G hutchinson-gilford progeria syndrome (HGPS) mouse model.
Remodelin hydrobromide (5 mg/kg, p.o.) shows a T1/2 of 1.81 hours and oral bioavailability (F%) of 43.5% in mice[3].
Pharmacokinetic parameters for Remodelin hydrobromide in Mice[1]

Route
Dose (mg/kg)
T1/2 (h)
Tmax (h)
Cmax (ng/mL)
AUC0-t (ng/h/mL)
AUC0-Ꝏ (ng/h/mL)
MRT_last (h)
F(%)

p.o.
5
1.81
0.25
409
235
259
0.84
43.5%

Reference

[1]. Larrieu D, et al. Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science. 2014 May 2;344(6183):527-32.
 [Content Brief]

[2]. Ma N, et.al. Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication. Int J Mol Sci. 2022 Jun 12;23(12):6573.
 [Content Brief]

[3]. Balmus G, et.al. Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Nat Commun. 2018 Apr 27;9(1):1700.
 [Content Brief]

[4]. Zhang X, et.al. N-Acetyltransferase 10 Enhances Doxorubicin Resistance in Human Hepatocellular Carcinoma Cell Lines by Promoting the Epithelial-to-Mesenchymal Transition. Oxid Med Cell Longev. 2019 Jul 1;2019:7561879.
 [Content Brief]