Lonafarnib is a synthetic farnesyltransferase inhibitor (FTI) and a small-molecule pharmaceutical compound. It inhibits farnesyltransferase, an enzyme involved in the post-translational modification of proteins containing a C-terminal CAAX motif.
Lonafarnib is particularly associated with the treatment of Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies. In these disorders, abnormal processing of lamin A contributes to the accumulation of a toxic protein called progerin. Inhibition of farnesylation reduces the abnormal membrane association of progerin and related mutant lamin A proteins.
Lonafarnib is a synthetic small-molecule compound with the molecular formula C27H31F2N3O and a molecular weight of approximately 465.56 g/mol. Its CAS Number is 193275-84-2.
The compound is a potent inhibitor of farnesyltransferase and is administered orally in its pharmaceutical formulation.
Lonafarnib selectively inhibits farnesyltransferase (FTase), which catalyzes the transfer of a farnesyl group to specific proteins.
In Hutchinson-Gilford progeria syndrome, a mutation in the LMNA gene leads to production of progerin, an abnormal form of lamin A. Progerin undergoes farnesylation and remains abnormally associated with the nuclear membrane.
By inhibiting farnesyltransferase, lonafarnib reduces progerin farnesylation and improves cellular and nuclear abnormalities associated with the disease.
Lonafarnib is used in approved pharmaceutical treatment for Hutchinson-Gilford progeria syndrome and certain processing-deficient progeroid laminopathies.
It is an orally administered therapy and is used under specialized medical supervision.
Lonafarnib API can be evaluated using validated analytical procedures for identification, assay, related substances, water content, residual solvents, elemental impurities and other applicable quality attributes.
Chromatographic and spectroscopic techniques may be used for identity, assay and impurity determination. Appropriate control of process-related impurities and degradation products should be incorporated into the applicable drug-substance specification.
Acceptance criteria should be based on the applicable manufacturer's drug-substance specification, Certificate of Analysis and relevant regulatory requirements.
Lonafarnib should be stored in a tightly closed pharmaceutical-grade container under controlled storage conditions. It should be protected from excessive heat, moisture and direct light.
Specific storage and transportation requirements should follow the applicable manufacturer's approved specification.
Lonafarnib API may be supplied for qualified pharmaceutical manufacturing, formulation development, analytical and research applications, subject to applicable quality and regulatory requirements.
Lonafarnib API is available for qualified pharmaceutical development and manufacturing requirements subject to applicable quality and regulatory standards. Customers can request product specifications, Certificate of Analysis, analytical documentation, packaging information and commercial details according to their requirements.
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |