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]. |
|
| ||||
| Ca2+ 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).