Drug intelligence / Profile preview

PIM447 + ruxolitinib + ribociclib

Development stage
Phase 1
Lead developer
Novartis
Modality
Small Molecules
Administration
Oral
01

Overview

PIM447 + ruxolitinib + ribociclib is a triple combination investigational regimen studied primarily in myelofibrosis. - **PIM447** (also called LGH447) is a pan-PIM kinase inhibitor; it blocks the activity of all three PIM kinases (PIM1, PIM2, PIM3), which are proto-oncogenes involved in promoting cell cycle progression and survival, particularly in hematologic malignancies[1][2][4][8]. - **Ruxolitinib** is a Janus kinase (JAK) inhibitor, mainly targeting JAK1 and JAK2, leading to inhibition of aberrant cytokine signaling and reduction of pathological cell proliferation in myeloproliferative disorders. - **Ribociclib** (LEE011, Kisqali) is a cyclin-dependent kinase inhibitor, specifically blocking CDK4 and CDK6, thereby preventing cell cycle progression from G1 to S phase in cancer cells[3][5][6][10]. This combination—administered orally—was tested in phase I trials specifically for the treatment of **myelofibrosis** to assess safety, tolerability, and preliminary efficacy[5][10]. All three components are **small molecule inhibitors** developed or manufactured by Novartis[7][10].

Other names
PIM kinase inhibitor LGH447ruxolitinibribociclib
02

Targets

ALK (Anaplastic lymphoma kinase receptor tyrosine kinase)GSK3 (Glycogen synthase kinase 3 beta)JAK1 (Janus kinase 1)JAK2 (Janus kinase 2)JAK3 (Janus kinase 3)NTRK2 (Tropomyosin-related kinase receptor type B)PIM1 (Proviral integration site for moloney murine leukemia virus kinase 1)PIM2 (Proto-oncogene serine/threonine-protein kinase Pim2)PIM3 (Proviral integration site for Moloney murine leukemia virus kinase 3)PRKCI (Protein kinase C iota)PAK1 (p21-activated kinase 1)RET (Rearranged during transfection receptor tyrosine kinase)SRC (Proto-oncogene tyrosine-protein kinase Src)TNK2 (Activated Cdc42-associated kinase 1)TYK2 (Tyrosine kinase 2)CDK4 (Cyclin-dependent kinase 4)CDK6 (Cyclin-dependent kinase 6)

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