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