Table 1.

Anti-MB drugs and candidates functioning through conventional MB-related targets (2010 to present).^a

Name	Structure	Mode of action	BBB permeable	In vitro model used	In vivo model used	Development Status^d	Reference
Pyrvinium		CK1α agonism	Yes	Hh-Light2 cells^a NIH3T3, Smo^D473H cells and Sufu^−/− MEFs^a	Ptch^+/− MB allografts	Preclinical	17
Fenretinide		Wnt3a/β-cateni n antagonism	Yes	Daoy and ONS-76 cells^e	Daoy or ONS-76 xenografts	Preclinical	19
Vismodegib (GDC-0449)		Smo antagonism	Yes	C3H10T1/2 MEFs^a	Ptch^+/− MB allografts	Phase II	27,28
Sonidegib (NVP-LDE225)		Smo antagonism	Yes	mSmo and hSmo^b	Ptch^+/−; p53^+/− MB subcutaneous/orthotopic allografts	Phase II	29
Glasdegib (PF-04449913)		Smo antagonism	Yes	C3H10T1/2 MEFs^a	Ptch^+/−; p53^+/− or Ptch^+/−; p53^−/− MB allografts	Preclinical	30,31
Taladegib (LY2940680)		Smo antagonism	Yes	C3H10T1/2 MEFs^a Smo^D473H transfected NIH3T3 cells^a Daoy cells^e	Ptch^+/−; p53^−/− transgenic mice	Phase I (Withdrawn)	32,33
NVP-LEQ506		Smo antagonism	Yes	mSmo and hSmo^b Smo^D473H transfected NIH3T3 cells^a	Ptch^+/−; Hic^−/− MB allografts	Phase I	34
MK-4101		Smo antagonism	Yes	Hh-Light2 cells^a Ptch^+/− mice-derived cells^e Smo^D477G cells^a	Ptch^+/− MB allografts Ptch^+/− mice bearing primary MB	Preclinical	35
12b		Smo antagonism	NA	Hh-Light2 cells^a	Ptch^+/−; p53^−/− MB allografts	Preclinical	36
TAK-441		Smo antagonism	NA	Hh-Light2 cells^a Smo^D473H transfected cells^a	Ptch^+/−; p53^−/− MB allografts	Phase I (Discontinued)	37–39
Itraconazole		Smo antagonism	Limited	Hh-Light2 cells^a ASZ001 cells^c	Ptch^+/−; p53^−/− MB allografts Smo^D477G MB allografts	Preclinical	40
Arsenic trioxide	As₂O₃	Gli antagonism	Yes	Daoy and D556 cells^e	ND2:SmoA1 transgenic mice Ptch^+/−; p53^−/− MB allografts Smo^D477G MB allografts	Phase II	47,48
MK-5710		Smo antagonism	NA	Hh-Light2 cells^a	Ptch^+/− MB allografts	Preclinical	49,50
PF-5274857		Smo antagonism	Yes	hSmo and Hh-dependent MEFs^a	Ptch^+/−; p53^+/− MB allografts	Preclinical	51
9d		Smo antagonism	NA	hSmo and mSmo^a	Ptch^+/− MB allografts	Preclinical	52
14f		Smo antagonism	NA	hSmo and mSmo^a	Ptch^+/− MB allografts	Preclinical	52
5		Smo antagonism	NA	Smo^WT and Smo^D473H transfected NIH3T3 cells^a	Ptch+^+/−; p53^−/−; Smo^D477G MB allografts	Preclinical	53
24		Smo antagonism	Yes	Hh-Light2 cells^a	Ptch^+/− MB subcutaneous xenografts	Preclinical	54
L-4		Smo antagonism	NA	Hh-Light2 cells^a Smo^D473H transfected cells^a	Ptch+^+/−; p53^−/− MB allografts	Preclinical	56
ANTA XV		Smo antagonism	Yes	TM3-Gli-Luc shift assay hSmo binding^a	Ptch+^+/−; p53^−/− MB allografts	Preclinical	57
43		Smo antagonism	NA	hSmo and mSmo binding^a	Ptch^+/−; p53^−/− MB allografts	Preclinical	58
27		Smo antagonism	NA	hSmo and mSmo binding^a	NOD-Scid mice	Preclinical	59
10e		Smo antagonism	NA	Hh-Light2 cells^a Ptch^+/−; p53^−/−mice-derived MB cells^e	Ptch^+/−; p53^−/− MB allografts	Preclinical	60
23b		Smo antagonism	NA	Hh-Light2 cells^a Ptch^+/−; p53^−/− mice-derived MB cells^e	Ptch^+/−; p53^−/− MB allografts	Preclinical	61
65		Smo antagonism	NA	Hh-Light2 cells^a	Ptch^+/−; p53^−/− MB allografts	Preclinical	62
CAT3		Smo antagonism	Yes	Daoy cells^e	Daoy orthotopic xenografts	Preclinical	63
E-1		Gli antagonism	NA	Sufu^−/− MEFs^a	Ptch^+/−; p53^−/− MB allografts	Preclinical	64
BRD9526		Gli downregulating	NA	Hh-Light2 cells^a	NA	Preliminary	65
29a		Gli downregulating	NA	Hh-Light2 cells^a	Ptch^+/−; p53^−/− MB allografts	Preclinical	66