Table 1.
Effect of IGF-1R targeting on receptor signaling and downregulation.
| Compound | IGF-1R Downstream Signaling | IGF-1R Downregulation |
β-arr Signaling |
||||
|---|---|---|---|---|---|---|---|
| pIGF-1R | pAKT | pERK | |||||
| Original Report |
Follow up | Original Report |
Follow up | ||||
| IGF-1R Monoclonal Antibodies | |||||||
| Cixutumumab (IMC-A12) |
↓ [20] | ↓ [20] | ↓ [20] | ↓ [26] | Yes [20] | ||
| Teprotumumab (R1507) |
↓ [21] | ↓ [21] | → [21] | ↑ [27] | Yes [21] | β-arr1 [27] | |
| Dalotuzumab (MK-0646) |
↓ [28] | NI | ↓ [29,30] | NI | → [30,31] | Yes [28,30] | |
| Ganitumab (AMG 479) |
↓ [32] | ↓ [32] | NI | → [33] | Yes [32] | ||
| Robatumumab (SCH717454) |
↓ [34] | ↓ [34] | ↓ [34] | ↓ [35] | Yes [34] | ||
| AVE1642 (EM164) |
↓ [36] | ↓ [36] | ↓ [36] | → [37] | Yes [36] | ||
| Figitumumab (CP-751) |
↓ [38] | ↓ [38] | NI | ↑ [39] → [40] |
Yes [38] | β-arr1 [39] | |
| αIR3 | ↓ [41] | NI | ↓ [42] | NI | ↓ [43] ↑ [44] |
NI | |
| Tyrosine Kinase Inhibitors | |||||||
| BMS-536924 | ↓ [45] | ↓ [45] | ↓ [45] | ||||
| OSI-906 (linsitinib) |
↓ [2] | ↓ [2] | ↓ [2] | ↓ [46] | NI | ||
| AXL1717 (PPP) |
↓ [47] | ↓ [47] | ↓ [47] | ↓ [48] ↑ [49] |
Yes [50] | β-arr [49] | |
| BMS-754807 | ↓ [51] | ↓ [51] | ↓ [51] | ↓ [52] | NI | NI | |
| AG-1024 (Tyrphostin) |
↓ [53] | NI | ↓ [54] | NI | ↓ [55] | NI | NI |
| NVP-AEW541 | ↓ [56] | ↓ [56] | ↓ [56] | ↓ [57,58] | NI | NI | |
| KW-2450 | ↓ [59] | ↓ [59] | ↓ [59] | NI | NI | ||
NI: Not investigated; ↓: inhibition; ↑: activation; →: no changes; β-arr: β-arr signal.