CP-609754

• CAT Number: I006240
• CAS Number: 1190094-64-4
• Molecular Formula: C29H22ClN3O2
• Molecular Weight: 479.96
• Purity: ≥95%
• Synonyms: 6-[(R)-(4-chlorophenyl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-(3-ethynylphenyl)-1-methylquinolin-2-one
• InChI: InChI=1S/C29H22ClN3O2/c1-4-19-6-5-7-20(14-19)24-16-28(34)33(3)26-13-10-22(15-25(24)26)29(35,27-17-31-18-32(27)2)21-8-11-23(30)12-9-21/h1,5-18,35H,2-3H3/t29-/m1/s1
• InChIKey: JAHDAIPFBPPQHQ-GDLZYMKVSA-N
• SMILES: CN1C=NC=C1C(C2=CC=C(C=C2)Cl)(C3=CC4=C(C=C3)N(C(=O)C=C4C5=CC=CC(=C5)C#C)C)O

CP-609754 (LNK-754) is a potent and reversible farnesyltransferase inhibitor with potential anticancer activity.The IC50 for inhibiting farnesylation of recombinant human H-Ras is 0.57 ng/mL and recombinant K-Ras is 46 ng/mL[1]. CP-609754 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
CP-609754 (CP-609,754) is a reversible inhibitor of farnesyltransferase with a slow on/off rate. CP-609,754 inhibits farnesylation (IC50=1.72 ng/mL) of mutant H-Ras in 3T3 H-ras (61L)-transfected cell lines with SDS-PAGE analysis of [35S]methionine-labeled material[1].?
CP-609754 is competitive for the prenyl acceptor (H-Ras protein) and noncompetitive for the prenyl donor farnesyl PPI. CP-609754 interacts with the farnesyltransferase-farnesyl PPI complex and competes for the binding of the Ras protein. CP-609754 selectively inhibits farnesylation of both H- and K-Ras proteins in 3T3 transfectants[1].
CP-609754 (CP-609,754) has antitumor activity against 3T3 H-ras (61L) tumors in vivo[1].?
With twice daily oral dosing of CP-609754, tumor regression is achieved with a dose of 100 mg/kg; the ED50 for tumor growth inhibition is 28 mg/kg[1].? ?
With continuous i.p. infusion of CP-609754, tumor growth is inhibited by >50%, and tumor farnesyltransferase activity inhibited by >30% in mice in which the plasma concentration of CP-609754 is maintained above 118 ng/mL[1].

Reference

[1]. Stacy L Moulder, et al. A phase I open label study of the farnesyltransferase inhibitor CP-609,754 in patients with advanced malignant tumors. Clin Cancer Res. 2004 Nov 1;10(21):7127-35.
 [Content Brief]