Target | Inhibitors | Type of malignancy | Highlights | Ref |
---|---|---|---|---|
PARP1 | Olaparib (AZD2281, MK-7339) | MCL and MLL-AF9 rearranged Leukemia cells | Higher sensitivity of double-deficient ATM/p53 MCL cells, compared to mono-deficient MCL cells in ATM | [106] |
AG14361 | MCL cells | Enhanced topotecan-induced apoptosis independent of TP53 status | [151] | |
PJ-34 | Patient-derived ATLL cells | p53-mediated caspase 3-dependent apoptosis | [155] | |
HL60, MOLT4, and K562 human leukemia cell lines | Synergistic effect in combination with histone deacetylase inhibitor, vorinostat | [156] | ||
BMN-673 (talazoparib) | Patient-derived CLL samples | Inhibited the proliferation of CLL cells independently of p53/ATM function | [158] | |
Primary AML samples AML mouse models | Enhanced apoptosis in combination with decitabine | [166] | ||
Veliparib (ABT-888) | Patients with relapsed/refractory lymphoma and MM | Enhances the cytotoxicity of bendamustine and rituximab | [161] | |
MM cells MM xenografts in SCID mice | Combined treatment with CDK inhibitor dinaciclib resulted in synthetic lethality of MM cells | [162] | ||
Acute leukemia, high-risk MPNs | Promising results in Combined treatment with topotecan and carboplatin in phase I study | [164] | ||
P10 | Human leukemic cell line Nalm6 | Induction of G2/M arrest and accumulation of DNA damage | [168] | |
DNA-PK | Wortmannin | Human leukemia cells | Sonolisib (PX-866) is Irreversible wortmannin analogue PWT-458 is PEGylated derivative of wortmannin | |
NU7026 | Primary CLL cells | Synergistic effects with chlorambucil | [195] | |
CC-115 | CLL, NHL, and MM | Phase I clinical trial A dual inhibitor of DNA-PK and mTOR | ||
IC86621 | NHL and HL | Synergistic effects with bleomycin and etoposide | [183] | |
CC-122 (Avadomide) | NHL and MM | Phase I clinical trial | ||
NU7441 | Pre-B ALL cells | Increase of chemosensitivity to doxorubicin | [198] | |
OK-1035 | L5178Y cells (lymphoma cell line) | Preclinical testing | [199] | |
Dbait (AsiDNA or DT01) | Lymphoma and leukemia cells | 32Â bp double-stranded DNA fragment that mimics DNA lesion and traps DNA repair enzymes A dual inhibitor of DNA-PK and PARP1 | [191] | |
GRN163L (Imetelstat) | CLL | Imetelstat sensitizes primary CLL lymphocytes to fludarabine A dual inhibitor of DNA-PK and telomerase | [192] |