Table 1.

Inhibitors of IGF-IR by drug class

DrugCompanyClassStatus
NotesCitations
PREINDIIIIII
Monoclonal antibodies
CP-751,871PfizerFully human IgG2 mabEmbedded ImageOngoing trials: phase I/II for pediatric patients with Ewing's sarcoma family of tumors. Phase Ib with docetaxel in HRPC. Phase II with exemestane in breast cancer, with Carbo/Taxol in NSCLC, with docetaxel/prednisone in HRPC. Phase II single agent in metastatic CRC.(29, 76, 86, 88, 95, 96)
IMC-A12ImcloneFully human IgG1 mabEmbedded ImageDevelopment with NCI-CTEP. Ongoing trials: phase I/II. Phase II single agent in HRPC and in Ewing's sarcoma family of tumors, in combination with cetuximab for CRC and H&N cancer.(25, 28, 9799)
R1507RocheFully human IgG1 mabEmbedded ImagePreviously known as RO4858696. Ongoing trials: phase I in pediatric patients. Phase II single agent in sarcomas.(26, 27, 100)
AMG-479AmgenFully human mabEmbedded ImagePhase II single agent in Ewing's sarcoma family of tumors and in combination with gemcitabine for pancreatic cancer.(30, 101, 102)
SCH-717454Schering-PloughFully human mabEmbedded ImagePreviously known as 19D12 (Medarex). Phase I trial done in healthy volunteers. Phase II single agent for CRC(85)
AVE-1642Sanofi-AventisHumanized mabEmbedded ImagePreviously known as EM164 (ImmunoGen)(22, 103105)
MK-0646Merk/Pierre FabreHumanized mabEmbedded ImagePreviously known as A2CHM, F50035, 7C10, or 7H2HM. Ongoing trials: phase II in combination with irinotecan/cetuximab in CRC.(21, 106108)
BIIB022Biogen IdecFully human nonglycosylated IgG4.P antibodyEmbedded ImageDevoid of Fc-effector function to eliminate potential Fc mediated toxicity to the normal vital organs.(109, 110)
Tyrosine kinase inhibitors
INSM-18Insmed and UCSFReversible ATP-competitiveEmbedded ImageOngoing phase I/II. Inhibits IGF-IR and HER2, and it could act as an inhibitor of transcription (blocking also cdc2, survivin, and VEGF). Initially developed by Erimos Pharmaceuticals (EM-1421 or Terameprocol).
OSI-906OSI PharmaceuticalsOral small molecule. Reversible ATP-competitiveEmbedded ImageDerived from compound-1, also known as PQIP.(111114)
XL-228ExelixisOral small moleculeEmbedded ImageInhibits bcr-abl, scr and IGF-IR. Ongoing phase I for CML and ALL. Also known as XL-2280(115, 116)
NVP-ADW742NovartisReversible ATP-competitiveEmbedded Image(39, 40, 117)
NVP-AEW541NovartisReversible ATP-competitiveEmbedded Image(37, 41, 93, 118120)
AG-1024MerkNon–ATP-competitiveEmbedded Image(121)
BMS-536924Bristol-Myers SquibbEmbedded Image(84)
BMS-554417Bristol-Myers SquibbOral small molecule. Reversible ATP-competitiveEmbedded Image(122)
BVP-51004BiovitrumOral small molecule. Non-ATP-competitiveEmbedded ImageAlso known as Cyclolignan PPP. Causes IGF-IR down-regulation, probably through the induction of ubiquitination.(123, 124)
Other
ATL-1101Antisense therapeuticsTopical Antisense oligonucleotideEmbedded ImageDeveloped for the treatment of psoriasis.
ANT-429AntyraHotSpot pharmaphoresEmbedded Image
  • Abbreviations: mab, monoclonal antibody; HRPC, hormone refractory prostate cancer; NSCLC, non–small cell lung cancer; CRC, colorectal cancer; NCI-CTEP, National Cancer Institute–Cancer Therapeutics Evaluation Program; H&N, head and neck; Fc, fragment crystallizable region; CML, chronic myelogenous leukemia; ALL, acute lymphocytic leukemia; PPP, picropodophyllin.