Table 2.

Anti-MB drugs and candidates functioning through epigenetic, phosphorylation, and other emerging targets (2010 to present). ^a

Name	Mode of action	BBB permeable	In vitro model used	In vivo model used	Development Status^d	Reference
Panobinostat (LBH589)	HDAC antagonism	Yes	UW228, UW426 and Med8A cells^e	UW426-effLuc MB leptomeningeal seeding model	Phase I	72
Mocetinostat	HDAC antagonism	Yes	Hh-Light2, Sufu^−/− MEFs^c Med1-MB cells^d	Primary Hh-MB allograft Ptch^−/− allografts	Preclinical	73
Dacinostat	HDAC antagonism	Yes	Daoy and D283 cells^d	Daoy xenografts	Preclinical	75
Quisinostat	HDAC antagonism	Yes	Daoy and D283 cells^d	Daoy xenografts	Preclinical	75
JQ1	BET-bromo domain antagonism	Yes	Med1-MB and Smo^WT-MB cells^c	Med1-MB allografts Smo^WT-MB and Smo^D477G-MB allografts MYC-amplified Grp3-MB xenografts	Preclinical	77–79
Birabresib	BET-bromodomain antagonism	Yes	HD-MB03, Daoy, ONS-76 and UW228^d	MYC-amplified HD-MB03 xenografts	Preclinical	80
I-BET151	BET-bromodomain antagonism	Yes	Hh-Light2 cells^a Sufu^−/− MEFs^c	Ptct^+/− MB allografts	Preclinical	81
GSK-LSD1	LSD1 antagonism	Yes	MG cells^d	MG flank allografts	Preclinical	85
CBL0137	FACT antagonism	Yes	D425, D458 and HD-MB03 cells^d	HD-MB03 flank/intracranial xenografts	Preclinical	87
Buparlisib	PI3K antagonism	Yes	Twelve MB cells^d	Daoy xenografts	Preclinical	93
Temsirolimus (TEM)	mTOR antagonism	Yes	Daoy cells^d	Daoy xenografts	Phase I	94–96
Milciclib	CDK2 antagonism	Yes	GTML2, MB002, Sd425 and D283 cells^d	GTML2 orthotopic xenografts MB002 xenografts	Preclinical	100
Palbociclib	CDK4/6 antagonism	Yes	Med-211FH cells^d	Med-211FH or Med-1712FH subcutaneous xenografts	Phase II	105
Silmitasertib	CK2 antagonism	Yes	MB21, MB55 and MB53 cells^c,e	Ptch^+/−; Tpr53^−/−; Smo^D477G MB allografts	Phase I/II	106
Prexasertib	CHK1 antagonism	Yes	Grp3-MB cells^f	orthotropic Grp3-MB xenografts	Phase I	109,110
RKI-1447	ROCK antagonism	NA	Nine MB cells^d	D425 xenografts	Preclinical	114
Adavosertib	WEE1 kinase antagonism	Limited	Daoy and UW228 cells^d	Daoy xenografts	Phase I/II	115,116
S29	Src kinase antagonism	NA	Daoy and D283-MED cells^d	Daoy xenografts	Preclinical	118
Dasatinib	Src kinase antagonism	Yes	Daoy and D556 cells^d	PS125 Hh-MB allografts	Phase I	120
Roflumilast	PDE4D antagonism	Yes	NIH3T3 cells^a	Smo^D477G-MB allografts	Preclinical	124
RK-33	DDX3 antagonism	NA	Daoy and UW228 cells^d	Daoy xenografts	Preclinical	125
Veliparib	PARP antagonism	Yes	NA	Pediatric MB orthotopic xenografts	Phase I	127–129
Tolfenamic acid	Sp1 degradation	Yes	Daoy and D283 cells^d	D283 subcutaneous xenografts	Preclinical	132
Lovastatin	HMG-CoA reductase antagonism	Yes	Daoy and D283 cells^d	Daoy subcutaneously/orthotopic xenografts	Preclinical	133,134
Simvastatin	HMG-CoA reductase antagonism	Yes	Daoy, D283, D341 and Ptck^+/− mice detived cell line^d	Ptch^+/− CB17/SCID subcutaneous allografts	Preclinical	135,136
Verapamil	ABC transporter antagonism	Yes	TE671and Daoy^d	Daoy xenografts	Preclinical	138,139
Celecoxib	COX-2 antagonism	Yes	D234-Med and D283-Med^e,f	D283-Med xenografts MB-DP orthotopic xenografts	Phase II	143
Ganciclovir	DNA polymerases antagonism	Yes	D234, D283-Med and UW228–3 cells^e,f	D283-Med xenografts	Preclinical	141,144
Fingolimod	PP2A agonism	Yes	D341, D384 and D425-Med	D425-Med xenografts	Preclinical	146
Phenformin	mGPD antagonism	Yes	Med1-MB^d	Med1-MB allografts	Preclinical	148
AEE788	VEGFR1/2 and HER1/2 antagonism	Yes	Daoy and D283 cells^d	Daoy, Daoy^Pt or Daoy^HER2 xenografts	Phase I (Discontinued)	149,151
Lapatinib	EGFR and HER2 antagonism	Limited	Daoy, D283, and VC312 cells^d	Daoy xenografts	Phase II (Lack of efficacy)	152,153
Nilotinib	Multi-target tyrosine kinases and Smo antagonism	Yes	MB-PDX and Daoy cells^d	MB-PDX xenografts	Preclinical	155
Foretinib	Multi-target tyrosine kinases antagonism	Yes	Daoy cells^d	Daoy and ONS76 subcutaneous xenografts Daoy orthotopic xenografts Transgenic model of primary Hh-MB	Preclinical	158
Piperlongumine (PL)	ROS generating Raf-1 and CDK2 antagonism	Yes	D425 and D458 cells^d	D458 Subcutaneous xenografts D425 intracranial xenografts	Preclinical	159,160
Alsterpaullone (ALP)	CDK1, CDK5 and GSK3P antagonism	Yes	D425 and D458 cells^d	D458 Subcutaneous xenografts D425 intracranial xenografts	Preclinical	159,160
Pazopanib	Multi-target tyrosine kinases antagonism	Yes	Daoy, MEB-Med-8A, D283 Med, D341 Med cells^d	MEB-Med-8A orthotopic xenografts	Phase I	161
AT-9283	Multi-target kinases antagonism	NA	Daoy and D556 cells^d	NA	Phase I	164,165
Digoxin	Erk and Akt modulating	Yes	Med8A and D283 cells^d	ICb-2555MB and ICb-1078MB orthotopic PDX models	Preclinical	166
Disulfiram	ROS generating MAPK agonism NF-κB antagonism	Yes	Daoy cells^d	Daoy intracranial xenografts	Preclinical	167–169
Mebendazole	Hh and VEGFR2 antagonism	Yes	Hh-Light2 and C3H10T1/2 cells^a Daoy and Smo^D477G MEFs cells^c,e	Daoy orthotopic xenografts Ptch^+/−, p53^−/−MB allografts D425 xenografts	Phase I/II	170,171