Table 1.

Tyrosine Kinase and Aurora Kinase Inhibitors Currently In Clinical Trials

Compound	Mechanism of Action	Clinical Trials	Data
Tyrosine kinase inhibitor
Bosutinib (SKI606; Wyeth, New York, NY)	ABL/SCR	Phase 2 trial	Imatinib-resistant-intolerant patients (N=295) had CHR, MCyR, and CCyR rates of 91%, 64%, and 50%, respectively, and favorable safety and tolerability profiles (Cortes 201070); binds both active and intermediate BCR-ABL conformations (Puttini 200691)
AP24534 (ARIAD Pharmaceuticals, Cambridge, Mass)a	Multikinase, including BCR-ABL	Phase 1 trial	Patients with Ph+ leukemia (N=44) treated with AP24534; 83% of evaluable patients with CML-CP achieved a CHR, 48% achieved an MCyR, 33% achieved a CCyR (Talpaz 201074); pancreatitis and increased lipase/amylase were DLTs (Cortes 200973)
Aurora kinase inhibitor
XL-228 (Exelixis, South San Francisco, Calif)a	Multikinase, including ABL, aurora kinase A, SFT, and IFGR1	Phase 1 dose-escalation trial	Patients (N=35) who failed multiple therapies (or with T315I) received weekly doses ranging from 0.45 to 10.8 mg/kg or 3.6 mg/kg twice weekly; 9 patients had T315I, and 5 patients had F317L; therapy was well tolerated up to 7.2 mg/kg/d; hyperglycemia and syncope were DLTs at 10.8 mg/kg/d; common grade 2 toxicities included hyperglycemia, fatigue, nausea, vomiting, and bradycardia; 7 of 35 patients (20%) responded (1 returned to CP, 2 had a minor CyR, 2 had an MCyR, and 2 had a CCyR); of the patients with T315I, 1 had a minor CyR, 1 had an MCyR, and 1 had a CCyR (Cortes 200875)
Apoptosis inhibitor
Omacetaxin mepesuccinate (OMAPRO; Chem-Genex Pharmaceuticals Ltd., Menlo Park, Calif)a	Inhibition of protein synthesis	Multicenter phase 2/3 trial	In 81 patients with CML who had T315I, the CHR, MCyR, and CCyR rates were 86%, 27%, and 18%, respectively, in patients with CML-CP; omacetaxine generally was well tolerated, with mainly hematologi toxicities (grade 3/4 thrombocytopenia [58%], anemia [36%], and neutropenia [33%]) (Cortes-Franco 200971)

ABL indicates the Abelson leukemia virus tyrosine kinase; SRC, tyrosine kinase encoded by the Rous sarcoma virus; CHR, complete hematologic response; MCyR, major cytogenetic response; CCyR, complete cytogenetic response; BCR, breakpoint cluster region; Ph+, Philadelphia chromosome positive; CML, chronic myeloid leukemia; CP, chronic phase; DLT, dose-limiting toxicity; SFT, simulator of Fe transport; IFGR1, insulin-like growth factor receptor 1; T315I, threonine to isoleucine mutation at codon 315; F317L, phenylalanine to leucine mutation at codon 317; CyR, cytogenetic response.

^aActive against T315I.