Lonafarnib

• CAT Number: I002472
• CAS Number: 193275-84-2
• Molecular Formula: C₂₇H₃₁Br₂ClN₄O₂
• Molecular Weight: 638.82
• Purity: ≥95%
• Target: Farnesyl Transferase
• Solubility: in DMSO > 10 mM
• Storage: Store at -20°C
• InChI: 1S/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1
• InChIKey: DHMTURDWPRKSOA-RUZDIDTESA-N
• SMILES: C1CN(CCC1CC(=O)N2CCC(CC2)C3C4=C(C=C(C=C4CCC5=CC(=CN=C35)Br)Cl)Br)C(=O)N

Lonafarnib(CAT: I002472), also known as SCH 66336 and trade name Zokinvy, is a medication used for the treatment of certain genetic disorders known as progeroid laminopathies, specifically Hutchinson-Gilford progeria syndrome (HGPS) and atypical progeroid syndrome (APS). It is a farnesyltransferase inhibitor that prevents the attachment of a farnesyl group to proteins, including progerin, which is responsible for the characteristic premature aging phenotype seen in progeroid laminopathies. Lonafarnib helps improve weight gain, increase bone density, and prolong survival in patients with HGPS and APS. It is typically administered orally in capsule form and its safety and efficacy have been demonstrated in clinical trials

Reference

1. Expert Opin Investig Drugs. 2012 Jul;21(7):1043-55. doi:
10.1517/13543784.2012.688950. Epub 2012 May 24.

Lonafarnib for cancer and progeria.

Wong NS(1), Morse MA.

Author information:
(1)National Cancer Centre Singapore, Department of Medical Oncology, Singapore.

INTRODUCTION: Lonafarnib is a non-peptidomimetic inhibitor of farnesyl
transferase, an enzyme responsible for the post-translational lipid modification
of a wide variety of cellular proteins that are involved in the pathogenic
pathways of various diseases including cancer and progeria. Although extensive
clinical research indicates limited activity of lonafarnib in solid tumors, there
is recent interest in combinations of farnesyl transferase inhibitors with
imatinib or bortezomib in hematological malignancies and to investigate the role
of lonafarnib in progeria.
AREAS COVERED: This review examines the in vitro and in vivo pharmacology of
lonafarnib and the available clinical data for lonafarnib monotherapy and
combination therapy in the treatment of solid and hematological malignancies as
well as progeria, using studies identified from the PubMed database supplemented
by computerized search of relevant abstracts from major cancer and hematology
conferences.
EXPERT OPINION: There is no evidence to support the use of lonafarnib in solid
tumors. There is ongoing interest to explore lonafarnib for progeria and to
investigate other farnesyl transferase inhibitors for chronic and acute
leukemias.

2. Expert Opin Investig Drugs. 2006 Jun;15(6):709-19.

Lonafarnib in cancer therapy.

Morgillo F(1), Lee HY.

Author information:
(1)M. D. Anderson Cancer Center, Department of Thoracic/Head & Neck Medical
Oncology, Houston, TX, USA.

Farnesyl transferase inhibitors (FTIs) are anticancer agents that were designed
to block the post-translational attachment of the prenyl moiety to C-terminal
cysteine residue of Ras and thus inactivate it. Because Ras plays an important
role in tumour progression and the ras mutation is one of the most frequent
aberrations in cancer, FTIs have been expected to exert excellent therapeutic
activities. Phase I and II clinical trials confirmed relevant antitumour activity
and low toxicity; however, no improvement in overall survival has been reported
in Phase III trials. The exact mechanism of action of this class of agents is
currently unknown. Increasing lines of evidence indicate that the cytotoxic
actions of FTIs are not due to the inhibition of Ras proteins exclusively, but to
the modulation of other targets, including RhoB, the centromere-binding proteins
and other proteins that have not yet been identified. This review describes the
pharmacological and clinical data as well as mechanisms of action of FTIs,
especially lonafarnib (SCH-66336), a non-peptidomimetic inhibitor that has shown
anticancer activity.