RYDAPT inhibits FLT3 and other tyrosine kinases that are drivers of AML1-6*
Watch the RYDAPT MOA video
RYDAPT binds to the catalytic domain of multiple receptor tyrosine kinases, including FLT3 (ITD, TKD, and wild type), KIT, PDGFRα/β, VEGFR2, and PKC, inhibiting mitogenic signalling of the respective growth factors in cells and resulting in growth arrest1
As a signalling gene, FLT3 activates signalling pathways that contribute to genetic alterations and reduced cell differentiation, which promote the development of AML7,8
In vitro data indicate that the clinical benefit of receptor tyrosine kinase inhibition is unknown.
AML, acute myeloid leukaemia; ATP, adenosine triphosphate; FLT3, FMS-like tyrosine kinase 3; ITD, internal tandem duplication; MOA, mechanism of action; PDGFRα/β, platelet-derived growth factor receptor α/β; PKC, protein kinase C; TKD, tyrosine kinase domain; VEGFR2, vascular endothelial growth factor receptor-2.
References: 1. RYDAPT [Summary of Product Characteristics]. Novartis Pharma AG; 2017. 2. Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med. 2005;353(2):172-187. 3. Rattu MA, Shah N, Iskhakova T, Popovitz B. The utility of FLT3 inhibitors in acute myeloid leukemia. US Pharm. 2014;39(11) (Specialty&Oncology suppl):8-11. 4. Foss B, Ulvestad E, Bruserud Ø. Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts. Eur J Haematol. 2001;67(4):267-278. 5. Trujillo A, McGee C, Cogle CR. Angiogenesis in acute myeloid leukemia and opportunities for novel therapies. J Oncol. 2012;2012:128608. 6. Altman A, Villalba M. Protein kinase C-θ (PKCθ): it's all about location, location, location. Immunol Rev. 2003;192:53-63. 7. Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152. 8. Fathi AT, Chabner BA. FLT3 inhibition as therapy in acute myeloid leukemia: a record of trials and tribulations. Oncologist. 2011;16(8):1162-1174.