Drug intelligence / Profile preview

cisplatin + pemetrexed + ruxolitinib

Development stage
Preclinical
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a combination regimen consisting of three drugs: - **Cisplatin** is a platinum-based chemotherapy agent that forms DNA crosslinks, leading to apoptosis in rapidly dividing cells. - **Pemetrexed** is an antifolate antineoplastic agent that inhibits multiple folate-dependent enzymes involved in the synthesis of thymidine and purine nucleotides, thereby disrupting DNA and RNA synthesis essential for cell replication[1][4][5]. - **Ruxolitinib** is a selective Janus kinase (JAK) inhibitor targeting JAK1 and JAK2, blocking cytokine signaling pathways involved in hematopoiesis and immune function. It reduces abnormal cell proliferation by inhibiting the JAK-STAT pathway[6][8][10]. Cisplatin plus pemetrexed is an established combination for non-squamous non-small cell lung cancer (NSCLC), mesothelioma, metastatic bladder cancer, and advanced cervical carcinoma. Ruxolitinib is approved for myelofibrosis, polycythemia vera, acute graft-versus-host disease (GVHD), chronic GVHD, atopic dermatitis (topical), and vitiligo (topical). The triple combination of cisplatin + pemetrexed + ruxolitinib does not have established clinical use or regulatory approval as a single regimen; its use would be investigational.

02

Targets

JAK3 (Janus kinase 3)GART (GAR transformylase)JAK2 (Janus kinase 2)TS (Thymidylate synthase)DNADHFR (Dihydrofolate reductase)JAK1 (Janus kinase 1)TYK2 (Tyrosine kinase 2)ATIC (Aminoimidazole carboxamide ribonucleotide transformylase)

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