Table 1.
Gamma-secretase inhibitors used for studies in hematological malignancies.
| Compound | Type of cancer cells tested | Type of studies | Biological effect reported | Reference |
|---|---|---|---|---|
| GSI-I (Z-LLNle-CHO, Calbiochem) | Burkitt lymphoma and diffuse large | In vitro | Growth suppression | Kogoshi et al. (2007) |
| B-cell lymphoma cell lines | Tohda et al. (2006) | |||
| AML cell lines | In vitro | Growth suppression | Kogoshi et al. (2007) | |
| T-ALL cell lines | In vitro | Growth suppression | Kogoshi et al. (2007) | |
| GSI-IX (DAPT, Calbiochem) | Burkitt lymphoma and diffuse large | In vitro | Growth suppression | Kogoshi et al. (2007) |
| B-cell lymphoma cell lines | Tohda et al. (2006) | |||
| AML cell lines | In vitro | Growth suppression | Kogoshi et al. (2007) | |
| T-ALL cell lines | In vitro | Growth suppression | Kogoshi et al. (2007) | |
| Mouse T-ALL cell lines | In vitro | G0/G1 cell cycle arrest and apoptosis | O’Neil et al. (2006) | |
| GSI-X (L-685,458 Calbiochem) | T-ALL cell line ALL-SIL (express ABL1 fusion protein) |
In vitro | Antagonized the inhibitory effect of imatinib on ALL-SIL cell proliferation |
De Keersmaecker et al. (2008) |
| GSI-XII (Z-IL-CHO, Calbiochem) | Burkitt lymphoma and diffuse large | In vitro | Growth suppression and apoptosis | Kogoshi et al. (2007) |
| B-cell lymphoma cell lines | Tohda et al. (2006) | |||
| MM cell lines and primary cells | In vitro | Apoptosis; increased cytotoxicity of doxorubicin | Nefedova et al. (2008) | |
| In vivo | Inhibition of RPMI-8226 and H929 tumor growth; increased anti-MM effect of doxorubicin and melphalan |
|||
| AML cell lines | In vitro | Induction of apoptosis | Kogoshi et al. (2007) | |
| T-ALL cell lines | In vitro | Induction of apoptosis | Kogoshi et al. (2007) | |
| GSI-XXI (Compound E, | T-ALL cell lines | In vitro | Cell cycle arrest in 5 out of 30 cell lines tested | Weng et al. (2004) |
| Calbiochem) | T-ALL cell line CUTLL1 | In vitro | G0/G1 cell cycle arrest and apoptosis | Palomero et al. (2006a,b) |
| T-ALL cell lines | In vitro | Reversible G0/G1 cell cycle arrest followed by apoptosis; Stimulation of T-ALL cell lines differentiation from CD4−/CD8+− to CD4+/CD8+ (MOLT-4) or changing expression of CD3; Antagonized the inhibitory effect of imatinib on ALL-SIL cell proliferation; Sensitized cells to dexamethasone |
De Keersmaecker et al. (2008) | |
| DAPT | MM cell lines, Hodgkin lymphoma cell line KM-H2 |
In vitro | Decrease in proliferation | Jundt et al. (2004) |
| GSI-15 (Acros Organics) | MM OPM-2 cell line | In vitro | Decrease in proliferation and induction of apoptosis; Inhibition of OCL activity |
Schwarzer et al. (2008) |
| MRK-003 (Merck) | T-ALL cell lines | In vitro | G0/G1 cell cycle arrest followed by apoptosis in 5 out of 20 cell lines tested |
O’Neil et al. (2007) |
| In vitro | G0/G1 cell cycle arrest followed by apoptosis in 3 cell lines tested |
Lewis et al. (2007) | ||
| MK-0752 (Merck) | T-ALL | Clinical trial | Results are not published yet | Deangelo et al. (2006) (abstract) |
GSI, γ-secretase inhibitor; T-ALL, T-cell lymphoblastic leukaemia; AML, acute myeloid leukaemia; MM, multiple myeloma; OCL, octeoclasts.