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ruxolitinib + buparlisib
- Development stage
- Discontinued
- Lead developer
- Novartis
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
The combination of **ruxolitinib** (a selective Janus kinase 1/2 inhibitor) and **buparlisib** (a pan-phosphatidylinositol 3-kinase [PI3K] inhibitor) was investigated in a phase 1b study for the treatment of intermediate- or high-risk myelofibrosis (MF). Ruxolitinib blocks JAK-STAT signaling, reducing abnormal blood cell proliferation and inflammatory cytokines. Buparlisib acts on all class I PI3K isoforms, targeting a pathway downstream of JAK that is often hyperactive in cancer and myeloproliferative neoplasms. The rationale for the combination is to simultaneously inhibit parallel proliferative and survival pathways in MF. The combination showed manageable safety but only modest efficacy, and further development has been discontinued[1][3][5][7].
- Other names
- ruxolitinib plus buparlisibbuparlisib + ruxolitinib
02
Targets
TYK2 (Tyrosine kinase 2)PIK3C3 (PI3K class III)JAK2 (Janus kinase 2)PIK3CD (Phosphatidylinositol 3-kinase delta)PIK3CA (Phosphoinositide 3-kinase alpha)DNA-PK (DNA-dependent protein kinase)JAK3 (Janus kinase 3)DCLK1 (Doublecortin-like kinase 1)TUBB (Tubulin (alpha and beta subunits))PI4KB (Phosphatidylinositol 4-kinase beta)JAK1 (Janus kinase 1)mTOR (Mammalian target of rapamycin kinase)PIK3CG (Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma)PIK3CB (Phosphatidylinositol 3-kinase beta subunit)
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