Table 4.

Microtubule stabilizer status in Alzheimer’s disease

S.no.	Drug	Clinical use	Dose and route	Side effect	Blood-brain barrier penetration	AD Status	Reference
1.	Paclitaxel	Ovarian, breast, and lung cancer, as well as Kaposi’s sarcoma	Preclinical •35 mg/m2 or 175 mg/m2 IV over 3 h every 3 weeks in ovarian cancer; 200 mg/m2IV over 3 h in lung cancer; 100 mg weekly, IV inKaposi’s sarcoma •10 or 25 mg/m2 i.p injections in mice for 12 weeks restored fast axonal transport in spinal axons	Neutropenia and peripheral neuropathy, neurotoxicity, and myelosuppression	Poor blood-brain barrier penetration	In vitro •10 nM in cell culture of mt-human-tau-induced hallmark cellular pathologies of AD •Restore axonal length at a low concentration 5 nm and decrease cell survival after OA treatment Preclinical •5 mg/kg i.p. in mice •10 or 25 mg/m2 i.p. in transgenic mice restored fast axonal transport in axons, wherein MT numbers and stable tubulin were increased	[358–366]
2.	Dictyostatin	Breast cancer, lung cancer	In vitro 10 and 100 nM in human lung adenocarcinoma and human breast cell lines.	Gastrointestinal complications and body weight loss	Good blood-brain barrier penetration	Preclinical •0.1 mg/kg was better tolerated in PS19 tau Tg mouse model •i.p. administration to CD1 mice (5 mg/kg) resulted in MT-stabilization	[367–372]
3.	Cabazitaxel	Refractory metastatic prostate cancer; Pediatric patient with refractory solid CNS tumors	Clinical •30 mg/m2 pediatric patients with CNS tumors •20 and 25 mg/m2 IV in patients with CRPC Preclinical •30 or 90 mg/m2 IV infusion in female CD2F1/CrlBR mice •15 or 60 mg/m2 in female Sprague–Dawley rats •15 mg/m2 in female Beagle dogs •15, 30, 45, or 90 mg m2 IV infusion in female mice •15 and 60 mg m2 IV infusion in rat •9,15, or 25 mg/kg i.p. in pediatric brain tumors	Febrile neutropenia, hypersensitivity reactions, thrombocytopenia, peripheral neuropathy	Good blood-brain barrier penetration. Poor substrate for the P-glycoprotein	NA	[373–376]
4.	TPI 287	Brain metastatic breast cancer	Preclinical •20 mg/kg IV in rats and mice Clinical Phase I20 mg/m2 IV	Peripheral neuropathy, weight loss	Good blood-brain barrier penetration	Clinical 2 mg/m2 in Patients with Primary Four Repeat Tauopathies	[377–379]
5.	Davunetide	Schizophrenia	Clinical 5 mg and 30 mg intranasal	NA	Good blood-brain barrier penetration Applicable to early stages of AD	Preclinical •2 μgNAP/mouse/day intranasally 2.5 μl for each nostril for 3 or 6 months •s.c. injections included l, 0.5 g/mouse/day •Intranasal 0.5 μg/5 μl/mouse/day 2.5 μl/each nostril Clinical •Phase II study •5 mg q.d and 15 mg b.i.d. intranasal in subjects with amnesic mild cognitive impairment and tauopathy	[380–388]
6.	CNDR-51657	Advanced Malignant Solid Tumors	Clinical Phase 1 22.5 and 18 mg/m2 in patients with refractory solid tumors	Neutropenia fever	Good blood-brain barrier penetration	Preclinical •1 or 5 mg/kg in female mice •10 mg/kg orally in mice •3 mg/kg or 10 mg/kg i.p. in mice for3 months In vitro Increased levels of acetylated tubulin at 1 μM and 10 μM in rat cortical neurons	[389–392]
7.	Peloruside A	Murine leukemic cells,	In vitro Cytotoxic to P388 murine leukemia cells at 10 ng/mL (18 nM)	NA	NA	In vitro 10 nM in neuronal culture	[393–396]
8.	Mapreg	Anti-depressant	Preclinical •50 mg/kg/day orally in tree shrews	Safe profile except body weight loss	NA	In vitro •1 μM PREG in neuronal culture •Tau (25 μg/ml) was incubated with 100 nM [3H]PREG	[397–399]

AD, Alzheimer’s disease; CNS, central nervous system; CRPC, castration-resistant prostate cancer; i.p., intraperitoneal; IV, intravenous; MT, microtubule.