Table 1.
Potency of lead cMet-ADC P3D12-vcMMAF in several cMet-positive cancer cell lines. Potency of P3D12-vc-MMAF, P1E2-vcMMAF, cMet kinase inhibitor PHA-665752 and Erlotinib was assessed in 8 cMet-positive cell lines and a negative control cell line. c-Met receptor number, c-Met copy number and exon 14 status is indicated for all 9 cancer cell lines.
| IC50 value for in vitro cytotoxicity(nM) and efficacy(%) |
c-Met expression, Copy Number Variation(CNV), exon14 status |
||||||
|---|---|---|---|---|---|---|---|
| MET | |||||||
| PHA-665752 | P1E2-vcMMAF | P3D12-vcMMAF | Erlotinib | c-Met expression no. c-Met (x10^3)/cell |
MET CNV CCLE putative(Log2) |
exon14 status |
|
| MKN-45 | 3.6(94.7%) | 0.28(97.6%) | 0.12(97.6%) | - | 700 | 2.63 | - |
| SNU-620 | 4.4(100.0%) | 0.10(84.6%) | 0.06(87.7%) | - | 850 | 4.54 | - |
| H1975 | - | 0.29(76.7%) | 0.03(76.2%) | 5,000 | 95 | 0.61 | - |
| SNU-16 | - | 1.19(91.3%) | 0.26(88.8%) | - | 95 | 0.69 | - |
| H441 | - | 0.04(47.8%) | 0.01(53.6%) | 5,000 | 140 | 0.72 | - |
| N87 | - | 0.26(59.1%) | 0.03(57%) | 1,700 | 19 | 0.13 | - |
| Hs-746 T | 1.3(75.0%) | 0.07(66.3%) | 0.01(64.8%) | - | 395 | 2.68 | deletion |
| H596 | - | 26.3(35.7%) | 0.13(37.5%) | 400 | 68 | −0.40 | deletion |
| SNU-1 | - | - | - | - | 0 | 0.03 | - |
Values are mean±standard deviation of three samples in cyctotoxicity.
Erlotinib: EGFR tyrosine kinase inhibitor.
MET Copy Number Variation data are from the Cancer Cell Line Encyclopedia (CCLE).