Drug intelligence / Profile preview

6-thioguanine + capecitabine + celecoxib + temozolomide

Development stage
Preclinical
Lead developer
Roche
Modality
Small Molecules
Administration
Oral, Intravenous
01

Overview

This is a combination regimen consisting of four small molecule drugs—6-thioguanine, capecitabine, celecoxib, and temozolomide. Each component has a distinct mechanism of action: - **6-thioguanine** is an antimetabolite and purine analog that interferes with DNA synthesis by being incorporated into DNA and RNA, leading to cytotoxicity primarily in rapidly dividing cells. It is mainly used in the treatment of acute myeloid leukemia but has been explored for other cancers, especially those with methylthioadenosine phosphorylase (MTAP) deficiency[1][2][3][4]. - **Capecitabine** is an oral prodrug that is converted to 5-fluorouracil (5-FU) in the body. 5-FU inhibits thymidylate synthase, disrupting DNA synthesis and repair. - **Celecoxib** is a selective cyclooxygenase-2 (COX-2) inhibitor used primarily as an anti-inflammatory agent but also investigated for its potential antitumor effects due to inhibition of prostaglandin synthesis. - **Temozolomide** is an alkylating agent that methylates DNA at the O6 and N7 positions of guanine residues, leading to apoptosis in cancer cells. This combination would be considered experimental; there are no known approved regimens or brand names for this exact four-drug combination. The rationale behind such combinations typically involves targeting multiple pathways involved in tumor growth or survival.

02

Targets

PTGS2 (Prostaglandin-Endoperoxide Synthase 2)IMPDH (Inosine-5'-monophosphate dehydrogenase 1)DNATS (Thymidylate synthase)

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