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Drug intelligence / Profile preview
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
DCLK1 (Doublecortin-like kinase 1)DNA-PK (DNA-dependent protein kinase)JAK1 (Janus kinase 1)JAK2 (Janus kinase 2)JAK3 (Janus kinase 3)PIK3CA (Phosphoinositide 3-kinase alpha)PIK3CB (Phosphatidylinositol 3-kinase beta subunit)PIK3CD (Phosphatidylinositol 3-kinase delta)PI4KB (Phosphatidylinositol 4-kinase beta)TYK2 (Tyrosine kinase 2)TUBB (Tubulin (alpha and beta subunits))PIK3C3 (PI3K class III)mTOR (Mammalian target of rapamycin kinase)PIK3CG (Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma)
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