Cell Cycle Inhibition without Disruption of Neurogenesis Is a Strategy for Treatment of Aberrant Cell Cycle Diseases: An Update

Table 1

Pharmacological approaches interfering with mitogenic molecules and signaling pathways of the “expanded cell cycle” in treatments of cancer and CNS diseases.

	Treatments
Targets	Cancers		CNS diseases
	Agents	Stages	Agents	Stages
CDK inhibitors	Flavopiridol,; Indisulam,; AZD5438; SNS-032; Bryostatin-1; Seliciclib; PD 0332991; SCH 727965; UCN-01,; Roscovitine,; AT7519	Clinical trials in a broad range of solid tumors and chronic lymphocytic leukemia (CLL) [13–16].	Flavopiridol; Olomoucine; Roscovitine; Quinazolines	Experimental trials in AD [18–22], PD [21], stroke [23, 24], TBI [25, 26], SCI [27, 28], excitotoxic stress [29–32], optic nerve transaction [33].
Antioxidants	Isoliquiritigenin	Experimental trials in prostate cancer [124].	Edaravone; NXY-059; Coenzyme Q10; Vitamin E; Melatonin; Trolox; SOD; NAC; PBN	Clinical use in stroke in Asia [125, 126], Clinical trials in stroke [126], AD [127–129], ALS [130–132].; Experimental trials in ALS [133], PD [134], SCI [135].
i/eNOS inhibitors	L-NAME; AMT; NPA	Experimental trials in prostate cancer [136].	L-NAME; AMT; NPA	Experimental trials in ICH [137], SCI [135].
Cox-2 inhibitors	Celecoxib; Rofecoxib; NS-398	Clinical trials in bladder cancer [138], lung cancer [139, 140], head and neck cancer [141], pancreatic cancer [142], prostate cancer [143], breast cancer [144], colorectal cancer [145].; Experimental trials in pancreatic cancer [146], prostate cancer [147], esophageal cancer [148], colon cancer [149].	Celecoxib; Rofecoxib; NS-398	Clinical trials in AD [150, 151].; Experimental trials in ICH [137].
Ca^2+ channel blockers	KYS05090	Experimental trials in cancers [152].	Flunarizine	Clinical trials in stroke [153].
Glutamatergic modulators	MK-801	Experimental trials in breast cancer [154], brain tumors [155].	Riluzole; Ceftriaxone; Talampanel; MK-801; NBQX	Clinical trials in ALS [156].; Experimental trials in TBI [157, 158], SCI [159], ICH [160], stroke [161].
NMDA-receptor modulators	AP5 Memantine	Experimental trials in breast cancer [154], gastric cancer [162].	Memantine	Clinical use in AD [163–166].; Clinical trials in ALS [156].; Off-label use in psychiatric disorders [167].; Experimental trials in TBI [168], ICH [169], stroke [170],
Thrombin inhibitors	Heparin	Experimental trials in lung cancer [171].	Heparin; Hirudin	Experimental trials in ischemic stroke [172], ICH [118, 173, 174].
Thrombin receptor-1 antagonist	RWJ-58259; SCH-79797	Experimental trials in colon cancer [175].	BMS-200261	Experimental trials in stroke [176]; PD [177].
Ras inhibitors	Lovastatin; FTS	Clinical trials in neurofibroma [178], head and neck cancer [179].; Experimental trials in neurofibroma [180], liver cancer [181], ovarian cancer [182], breast cancer [183], prostate cancer [184], lung cancer [185].	Lovastatin; Exoenzyme	Clinical trials in acute ischemic stroke [186, 187].; Experimental trials in motor neuron disorders [188, 189].
Src Inhibitors	KX-01; Dasatinib; PP1; PP2; Saracatinib	Clinical trials in breast cancer [190–192].; Experimental trials in breast cancer [193], lung cancer [194, 195], cervical cancer [196], renal cancer [197], prostate cancer [198].	PP1; PP2	Experimental trials in ICH [91, 199], AD [70].
JAK/Stat Inhibitors	EGCG; WP-1034	Experimental trials in prostate cancer [200], breast cancer [201], lung cancer [202], pancreatic cancer [203], acute myeloid leukemia [204].	EGCG	Experimental trials in AD, PD, HIV associated Dementia, multiple sclerosis (MS), ALS, or Pick’s Disease [79].
GSK-3β inhibitors	Lithium; SB 415286; SB 216763; AR-A014418	Experimental trials in colon cancer [205], neuroblastoma [206].	L803-mt; Lithium; Kenpaullone; Indirubin; SB 216763; SB 415286	Experimental trials in AD [207–212], PD [213], brain injury [214].; Clinical trials in ALS [156, 215].
PI3K inhibitors	NVP-BEZ235; GSK2126458	Experimental trials in breast cancer [216].	LY 294002	Experimental trials in AD [217], PD [218].
Akt Inhibitors	Perifosine; MK-2206; RX-0201; PBI-05204; GSK2141795	Clinical trials in advanced cancer [219, 220].	LY 294002	Experimental trials in AD [217], PD [218].
m-TOR	Everolimus; Temsirolimus	Clinical use in pancreatic cancer [221], renal cancer [221].; Clinical trials in epithelial ovarian cancer/primary peritoneal cancer [222], Endometrial Cancer [223], glioblastoma [224], breast cancer [225], neuroendocrine tumours [226], lung cancer [227], bladder cancer [228], renal cancer [229, 230].	Rapamycin	Experimental trials in AD [231], PD [232], TBI [233, 234], SCI [235, 236], stroke [237].
Tau inhibitor	SG410	Experimental trials in pancreas cancer [238].	TRx-0014	Clinical use in AD [239, 240].
ERK1/2 kinase pathway	PD98059	Experimental trials in prostate cancer [241], lung cancer [242].	PD98059	Experimental trials in ICH [72, 92].
P38 kinase pathway	SB203580	Experimental trials in colon cancer [243].	SB203580; SB239063	Experimental trials in ICH [92], PD [244], stroke [245].
JNK kinase pathway	SP600125	Experimental trials in cancer cells [246, 247].	CEP-1347; Colostrinin; SP600125	Experimental trials in ICH [72, 92], AD [248, 249], stroke [250], PD [248, 250].

4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine (PP1), 4-Amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide (PP2), 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride (AMT), 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo [f]quinoxaline-2,3-dione (NBQX), Dl-2-amino-5-phosphonovaleric acid (AP5), Epigallocatechin-3-gallate (EGCG), Farnesylthiosalicylic acid (FTS), Methylthioinnium chloride (TRx-0014), 5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK 801), N-acytyl-L-cysteine (NAC), N(G)-nitro-l-arginine methyl ester (l-NAME), N(omega)-propyl-l-arginine (NPA), Phenyl-N-tert-butylnitrone (PBN), Superoxide dismutase (SOD).