Table 16.2.
Combination of non-genotoxic p53 activators or MDM2 antagonists with targeted therapeutic agents
| Drug 1 | Target 1 | Drug 2 | Target 2 | In vitro evidence | In vivo evidence | Status | Reference |
|---|---|---|---|---|---|---|---|
| Nutlin | M2-p53 interaction |
Inauhzin | SIRT1 inhibitor | H460 and HCT116 cells | HCT116 xenografts |
Preclinical | [128] |
| Nutlin-3 | M2-p53 interaction |
Vorinostat, NaB, MS-275, Apicidin |
HDAC1 inhibitor | A549 and A2780 | Preclinical | [156] | |
| Nutlin-3 | M2-p53 interaction |
Sorafenib | Multi-kinase inhibitor | RCC, acute myeloid leukemic |
[157–159] | ||
| Nutlin | M2-p53 interaction |
17AAG | Hsp90 inhibitor | RKO, AGS, HCT116 MCF7, U20S | Xenografts? | [160] | |
| Nutlin-3 | M2-p53 interaction |
Dasatinib | Multi-kinase inhibitor | Primary B-CLL cell & cell line |
[161] | ||
| Nutlin-3 | M2-p53 interaction |
Imatinib | BCR/ABL tyrosine kinase inhibitor |
B210, IL-3 | [162] | ||
| Nutlin-3 | M2-p53 interaction |
VX-680 | Aurora kinase inhibitors |
A549, HCT116 | [163] | ||
| MI-219 | M2-p53 interaction |
ZnCl2, TPEN | Zinc chelator | HCT116, MCF-7 | [164] | ||
| Nutlin-3 | M2-p53 interaction |
1396-11, XIAP antisense oligonucleotide (ASO) |
XIAP inhibitor | OCI-AML3,MOLM-13, HL-60 |
Phase I clinical trial |
[165] | |
| Nutlin-3 | M2-p53 interaction |
Bortezomib | Proteasome inhibitor | MCL, HCT116, U20S | [166–170] | ||
| Nutlin-3 | M2-p53 interaction |
Velcade | Proteasome inhibitor | Myeloma (MM) | [171] | ||
| Nutlin-3 | M2-p53 interaction |
Valproic acid (VPA) |
HDAC1 inhibitors | AML cell lines | MOLM-13 orthotopic and xenograft |
[172] | |
| Nutlin-3a | M2-p53 interaction |
ABT-737 | Bcl-2 protein inhibitor | OCI-AML-3 and MOLM-13 |
[173] | ||
| Nutlin-3 | M2-p53 interaction |
MK-0457 | Aurora kinase inhibitors |
OCI-AML-3 and MOLM-13 | [174] | ||
| Nutlin | M2-p53 interaction |
PI-103 | PI3K/mTOR inhibitor | AML cells | Preclinical | [175] | |
| Nutlin-3 | M2-p53 interaction |
Mithramycin | Spl DNA binding inhibitor |
Gynecologic cancer cells | Xenografts | Preclinical | [176] |
| Nutlin-3 | M2-p53 interaction |
5-FU cisplatin | Suicide inhibitor, crosslinking of DNA |
Gastric cancer cell, OVCa cells |
Xenografts | [177, 178] | |
| Paclitaxel | AKT-M2-p53 | Beta-lapachone (LPC) |
(Topo I) | Retinoblastoma (Y79 cells) | [179] | ||
| (PTX) Nutlin-3a | M2-p53 interaction |
Roscovitine and DRB |
CDK inhibitors | ARN8 cells | [180] | ||
| Nutlin-3 | M2-p53 interaction |
SiMDMX | MDMX | A549, U20S, SJSA MCF-7, JEG3 |
[181] | ||
| Nutlin-3 | M2-p53 interaction |
Doxil | Intercalating DNA | RKO, HT-29 | [182] | ||
| MI-63 | M2-p53 interaction |
Gemcitabine | RNR inhibitor | MCL cell | Xenografts | Preclinical | [183] |