Table 1.

Summarizes the main inhibitors that target proteins of the DNA damage response. For each compound, existing clinical trials have been noted, focusing on those involving GBM patients where possible. Further, pharmacologically relevant characteristics such as the drug’s availability and blood–brain barrier (BBB) permeability have been highlighted.

Kinase	Inhibitor	Clinical Trial Phase	End Date	Drug Combinatory Strategy	Characteristics	BBB Permeability	Tumors/Cell Lines	Reference
ATM	KU55933	Pre-clinical	-	+IR +etoposide phosphate	Poor aqueous solubility and poor bioavailability	no	Human cervical cancer (HeLa), Human osteosarcoma (U2OS)	[33,94]
	KU60019	Pre-clinical	-	-	Poor aqueous solubility and poor bioavailability	no	Human glioma (U87, U1241)	[34]
	CP466722	Pre-clinical	-	+temozolomide	Improved aqueous solubility and bioavailability	no	Human breast cancer cell line (MCF7), fibroblasts (HFF), A-T cells, GBM12 glioblastoma xenograft cell lines	[35]
	KU59403	Pre-clinical	-	+irinotecan +etoposide phosphate	Improved aqueous solubility and bioavailability	no	Human colon cancer (HCT116, SW620), Human osteosarcoma (U2OS), Human breast cancer (MDA-MB-231)	[41]
	AZ32	Pre-clinical	-	+IR	Good bioavailability	yes	Human glioma (U87, LN18, T98G, …, A172)	[36]
	AZD0156	Phase-I NCT02588105 clinicaltrials.gov	30 April 2020	+olaparib +irinotecan	-	yes (poor)	Various metastatic solid tumours (including gastric adenocarcinoma, colorectal cancer)	[95]
	AZD1390	Phase-I NCT03423628 clinicaltrials.gov	05 April 2022	+IR	Good bioavailability	yes	Primary and recurrent glioblastoma multiforme	[38]
ATR	VE-821	Pre-clinical	-	+cisplatin	-	yes (poor)	Hamster ovarian cells (AA8), hamster lung fibroblasts (V79), human glioblastoma multiforme (M059J)	[47]
	NU-6027	Pre-clinical	-	+cisplatin +PARPi +hydroxyurea	-	unclear	Breast cancer, pancreatic cancer, ovarian cancer	[96]
	AZ20	Pre-clinical	-	monotherapy	Poor aqueous solubility	yes (poor)	Colorectal adenocarcinoma cell line (HT29), glioblastoma CSCs	[55,97]
	VX-970	Phase-I NCT02157792 clinicaltrials.gov	11 March 2020, 30 April 2025	monotherapy +cisplatin	-	unclear	Advanced solid tumors	[50,51]
	BAY1895344	Phase-I NCT03188965 clinicaltrials.gov	25 March 2022	monotherapy	-	unclear	Solid cancers and lymphomas	[52]
	AZD6738	Phase-II NCT03682289 clinicaltrials.gov	19 March 2023	+olaparib	Good oral bioavailability	yes (good)	Renal and pancreatic carcinoma, glioma initiating cells	[49,53]
DNAPK	M3814	Phase-I NCT02316197 NCT02516813 clinicaltrials.gov	19 December 2020	monotherapy +IR +cisplatin +doxorubicin	Orally bioavailable	unclear	CLL and solid tumors	[69,70]
	CC-115	Phase-I NCT02977780 clinicaltrials.gov	May 2022	+neratinib +temozolomide	-	yes (good)	Glioblastoma multiforme	[73]
Chk2	PV1019	Pre-clinical	-	+IR +topotecan	Good bioavailability	yes (good)	Human breast cancer (MCF7), Human ovarian cancer (OVCAR-3,-4,-5,-8), Human glioblastoma (U251)	[43]
	CCT241533	Pre-clinical	-	+bleomycin +olaparib +IR	Good bioavailability	yes (good)	Human colorectal cancer (HT-29), human breast cancer (MCF7), human glioblastoma (U87MG), human ovarian cancer line (OVCAR-3,5)	[44]
Chk2/Chk1	AZD7762	Phase-I NCT00473616 clinicaltrials.gov	February 2011, terminated due to cardiotoxicity	+irinotecan	-	unclear	Solid advanced tumors, glioblastoma primary isolates (pre-clinical)	[45]
Chk1	LY2606368	Phase-I NCT04023669 clinicaltrials.gov	June 2026	+gemcitabine +cyclophosphamide	Good oral bioavailability	unclear	Advanced solid tumors, medulloblastoma	[60]
	SRA737	Phase-I/II NCT02797964 NCT02797977 clinicaltrials.gov	28 October 2019	monotherapy +cisplatin +gemcitabine	Good oral bioavailability	unclear	Advanced solid tumors, Non-Hodgkin’s lymphoma	[59]
Wee1	MK-1775	Phase-I NCT02207010 NCT01849146 clinicaltrials.gov	May 2018, 28 September 2020	monotherapy +IR +temozolomide	Good oral bioavailability	yes (good)	Recurrent glioblastoma, Glioblastoma xenografts, Human glioblastoma cell line (U251, U87MG, T98G)	[66,67,68]
PARP	Rucaparib	Phase II NCT01891344 Phase III NCT01968213 clinicaltrials.gov	31 October 2021 June 2020	monotherapy	Good oral availability	yes (poor)	Ovarian cancer, Epithelial ovarian cancer, Fallopian tube cancer	[83,84,98,99]
	Niraparib	Phase I NCT01294735 Phase II NCT03307785	May 2012 February 2020	monotherapy +temozolomide +bevaciumab +carboplatin	Good bioavailability	yes (good)	Melanoma, Glioblastoma Multiforme, Metastatic solid tumors	[85]
	Veliparib	Phase I NCT01514201 Phase II NCT03581292 Phase III NCT02152982	28 March 2018, 29 October 2024, 14 January 2021	+IR +temozolomide	Good oral bioavailability	yes (good)	Newly diagnosed Glioblastoma and glioma	[86]
	Olaparib	Phase II NCT03233204 Phase II NCT02974621 Phase IINCT 03212274 Phase I NCT03212742	30 September 2024, 31 May 2020, 31 July 2020, 30 June 2022	monotherapy +bevacizumab +IR +temozolomide	Good oral bioavailability	yes (poor)	Non-hodgkin lymphoma, Advanced solid tumours, Glioma	[89,90]