VX-984

• CAT Number: I010067
• CAS Number: 1476074-39-1
• Molecular Formula: C23H23N7O
• Molecular Weight: 415.497
• Purity: ≥95%
• Synonyms: VX-984; VX 984; VX984.;(S)-N-methyl-8-(1-((2/’-methyl-[4,5/’-bipyrimidin]-6-yl-4/’,6/’-d2)amino)propan-2-yl)quinoline-4-carboxamide
• Target: PI3K/Akt/mTOR
• Solubility: Soluble in DMSO
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: 8-[(2S)-1-[[6-(4,6-dideuterio-2-methylpyrimidin-5-yl)pyrimidin-4-yl]amino]propan-2-yl]-N-methylquinoline-4-carboxamide
• InChI: InChI=1S/C23H23N7O/c1-14(17-5-4-6-18-19(23(31)24-3)7-8-25-22(17)18)10-28-21-9-20(29-13-30-21)16-11-26-15(2)27-12-16/h4-9,11-14H,10H2,1-3H3,(H,24,31)(H,28,29,30)/t14-/m1/s1/i11D,12D
• InChIKey: PEACIOGDEQRHFA-KIYKJNLWSA-N
• SMILES: CC1=NC=C(C=N1)C2=CC(=NC=N2)NCC(C)C3=CC=CC4=C(C=CN=C43)C(=O)NC

VX-984 (CAT: I010067) is a potent and selective inhibitor of DNA-dependent protein kinase (DNA-PK). DNA-PK is an enzyme involved in DNA repair and plays a crucial role in maintaining genomic stability. By inhibiting DNA-PK, VX-984 may impair the repair of DNA damage and sensitize cancer cells to DNA-damaging agents, such as chemotherapy or radiation therapy. This targeted approach aims to enhance the efficacy of cancer treatments and potentially overcome resistance mechanisms. VX-984 represents a promising candidate for further development in the field of cancer therapy, particularly in combination with other DNA-damaging modalities.

Overview of Clinical Research

Originator: Vertex Pharmaceuticals
Developer: Merck KGaA
Class: Antineoplastics
Mechanism of Action: DNA activated protein kinase inhibitors; DNA repair enzyme modulators
Orphan Drug Status: No

Reference

1. ChemMedChem. 2017 Jun 21;12(12):895-900. doi: 10.1002/cmdc.201700143. Epub 2017
May 29.

Targeting DNA-Dependent Protein Kinase for Cancer Therapy.

Harnor SJ(1), Brennan A(1), Cano C(1).

Author information:
(1)Northern Institute for Cancer Research, Newcastle University, School of
Chemistry, Bedson Building, Newcastle upon Tyne, NE1 7RU, UK.

The catalytic activity of DNA-dependent protein kinase (DNA-PK) is critical to
its ability to repair lethal DNA double-strand breaks (DSBs). This includes
repair of DSB lesions resulting from oxidative stress, oncogene-induced
transcription, or following therapeutic treatment of cancer cells. Armed with
this knowledge, many attempts have been made to identify small-molecule
inhibitors of DNA-PK activity as an approach to induce tumour chemo- and
radiosensitisation. This review examines the structures of known reversible and
irreversible inhibitors, including those based on chromen-4-one, arylmorpholine,
and benzaldehyde scaffolds. DNA-PK catalytic inhibitors, such as VX-984
(8-[(1S)-2-[[6-(4,6-dideuterio-2-methylpyrimidin-5-yl)pyrimidin-4-yl]amino]-1-met
hylethyl]quinoline-4-carboxamide) and M3814
((S)-[2-chloro-4-fluoro-5-(7-morpholinoquinazolin-4-yl)phenyl]-(6-methoxypyridazi
n-3-yl)methanol), have now progressed into clinical development which should help
to further advance our understanding of whether this approach is a promising
therapeutic strategy for the treatment of cancer.