The Hedgehog signalling pathway in breast development, carcinogenesis and cancer therapy

Hui, Mun; Cazet, Aurélie; Nair, Radhika; Watkins, D Neil; O'Toole, Sandra A; Swarbrick, Alexander

doi:10.1186/bcr3401

Breast Cancer Research

Table 1 Hedgehog pathway inhibitors in preclinical studies and current clinical trials

From: The Hedgehog signalling pathway in breast development, carcinogenesis and cancer therapy

Classification	Compound (Company)	Origin	Target	Patient population		Development stage	References
Experimental antagonists	Robotnikinin	Macrocycle	HH	-		Preclinical	[88]
	Cyclopamine	Veratum californicum	SMO	-		Preclinical	[75, 76]
	HhAntag	Benzimidazole derivative	SMO	-		Preclinical	[5]
	Compound5	Bis-amide class	SMO	-		Preclinical	[82]
	GANT58	Thiophene core with four pyridine rings	GLI	-		Preclinical	[84]
	GANT61	Hexahydro-pyrimidine derivative	GLI	-		Preclinical	[84]
	HIP1-4	Unknown	GLI	-		Preclinical	[85]
	Zerumbone	Zingiber zerumbet	GLI	-		Preclinical	[85]
	Arcyriaflavin C	Arcyria ferruginea	GLI	-		Preclinical	[85]
	Physalin F	Physalis minima	GLI	-		Preclinical	[85]
	Arsenic trioxide	Arsenic	GLI	-		Preclinical	[86, 87]
Neutralising antibody	5E1	Hybridomas	HH	-		Preclinical	[40]
Small molecules in current clinical trials	GDC-0449/Erivedge/vismodegib(Genentech/Roche/Curis)	Benzimidazole derivate	SMO	Skin	Basal cell carcinoma Basal cell nevus syndrome Breast	Phase I-III (FDA approved)	[77]
				CNS/brain/head and neck	Medulloblastoma Glioblastoma
				Aero-and gastrodigestive tract	Lung cancer Oesophagus Stomach Colorectum Pancreas
				Genital tract	Ovarian Prostate
				Blood	Multiple myeloma
				Soft tissue	Chondrosarcoma
	LDE225 (Novartis)	Unknown	SMO	Skin	Basal cell carcinoma Basal cell nevus syndrome Breast	Phase I-II	[77]
				CNS/brain/head and neck	Medulloblastoma Glioblastoma Neuroblastoma Astrocytoma
				Aero-and gastrodigestive tract	Lung cancer Colorectum Pancreas
				Blood	Chronic myelogenous leukemia
				Soft tissue	Rhabdomyo-sarcoma
	LEQ506 (Novartis)	Unknown	SMO	Skin	Basal cell carcinoma	Phase I	[77]
				CNS/brain/head and neck	Medulloblastoma
	IPI-926 (Infinity Pharma)	Cyclopamine	SMO	Skin	Basal cell carcinoma	Phase I-II	[77]
				CNS/head and neck	Head and neck cancer
				Aero-and gastrodigestive tract	Pancreas
				Soft tissue	Chondrosarcoma
	BMS-833923 (BMS/Exelixis)	Unknown	SMO	Skin	Basal cell carcinoma Basal cell nevus syndrome	Phase I-II	[77]
				Aero-and gastrodigestive tract	Lung cancer Oesophagus Stomach
				Blood	Acute myeloid leukemia Chronic myelogenous leukemia
	Itraconazole/Sporanox^® (Johnson &Johnson)	Triazole antifungal	SMO	Skin	Basal cell carcinoma Breast	Phase I-II (FDA approved)	[77, 83]
				CNS/brain/head and neck	Neuroblastoma
				Aero-and gastrodigestive tract	Lung cancer
				Genital tract	Prostate
				Blood	Leukemia Myelodysplastic syndromes
	PF-04449913 (Pfizer)	Unknown	SMO	Blood	Acute myeloid leukemia Myelodysplastic syndrome	Phase I-II	[77]
	TAK-441 (Millenium)		SMO	Skin	Basal cell carcinoma	Phase I	[77]

CNS, central nervous system; GLI, Glioma-associated oncoprotein; HH, Hedgehog; SMO, Smoothened.

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