Lonafarnib by aseem
Download as PPTX, PDF1 like833 views
Lonafarnib is a farnesyl transferase inhibitor that was studied in phase 2 clinical trials from 2007-2012 at Boston Children's Hospital for the treatment of Hutchinson-Gilford progeria syndrome. The trials involved doses of 100-175mg taken twice daily for 4-24 months. Lonafarnib works by inhibiting farnesyl transferase and preventing the farnesylation and activation of proteins involved in progerin production. The initial trials showed improvements such as reduced risks of stroke, headaches, increased height, and reduced bone fractures. However, dose-limiting toxicities included neutropenia, diarrhea, nausea and vomiting.
Lonafarnib by aseem
- 1. LONAFARNIB
- 2. Introduction • Sarasar (US) / SCH 66336 • C27H31Br2CIN4O2 ; FTIs • Tricylic derivative of Piperidine-Carboxamide • Initially developed for Neoplasms
- 3. Clinical Trial • In Phase 2 Clinical Trials (Interventional / NonRandomized / Open Label Study) for Usage in HGPS @ Baston Children Hospitaql , USA by Cayman Chemicals 2007-2012 with Pravastatin and Zoledronic Acid • 100 – 175mg (125) PO BD X 04 – 24 Months • 115 – 150 mg / m2
- 4. Mechanism of Action • Farnesyl transferase- Inhibitor (FTI) • Farnesyl gp attaches to Prelamin-A and prevents conversion to mature Lamin A PROGERIN (LMNA gene mutation) Lobular nuclei • FT post-translational modification and activation of oncogenic-signalling Ras proteins (subtypes H, N, K)
- 5. • aa
- 6. Initial Trials show clinical improvement :- Reduces Prevalence of TIA / CVA Reduces headache Improves height Reduces rigidity of bones / Incidence of Fractures
- 7. ADRs • Dose-limiting toxicity was Neutropenia • Diarrhea • Nausea • Vomiting • Altered Taste Sensation
- 8. THANK YOU