MPT0G211 is a potent, orally bioactive and selective HDAC6 inhibitor (IC50=0.291 nM). MPT0G211 is 1000-fold more selective for HDAC6 than other HDAC isoforms. MPT0G211 can cross the BBB (blood-brain barrier). MPT0G211 improves tau phosphorylation and cognitive deficits in AD/Alzheimer's disease models. MPT0G211 has anti-metastatic and neuro-protection effects. anti-cancer activity.

Physicochemical Properties

Molecular Formula	C17H15N3O2
Molecular Weight	293.319903612137
Exact Mass	293.116
CAS #	2151853-97-1
Related CAS #	MPT0G211 mesylate;2151854-33-8
PubChem CID	132157820
Appearance	Light yellow to khaki solid powder
LogP	2.5
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	22
Complexity	369
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C=CC(=CC=1)CNC1=CC=CC2=CC=CN=C12)NO
InChi Key	BPDQUKCPNSRTTR-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H15N3O2/c21-17(20-22)14-8-6-12(7-9-14)11-19-15-5-1-3-13-4-2-10-18-16(13)15/h1-10,19,22H,11H2,(H,20,21)
Chemical Name	N-hydroxy-4-[(quinolin-8-ylamino)methyl]benzamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	HDAC6 0.291 μM (IC50)
ln Vitro	The phosphorylation of tau Ser396 is greatly inhibited by MPT0G211 (0.1 μM; cells were transfected with pCAX APP 695 and pRK5-EGFP-Tau P301L for 24 hours)[1]. Inhibiting HDAC6/Hsp90 binding, MPT0G211 leads to the proteasomal breakdown of polyubiquitinated proteins[1]. Tau phosphorylation is markedly reduced by MPT0G211 through GSK3β inactivation[1]. h using pRK5-EGFP-Tau P301L and pCAX APP 695)[1]. The proliferation of MDA-MB-231 and MCF-7 cells is inhibited by MPT0G211 (GI50 = 16.19 and 5.6 μM, respectively)[2]. Through the inhibition of DNA repair mechanisms and the activation of Bcl-2-associated X protein (BCL-XL)-dependent cell apoptosis, MPT0G211 enhanced the cytotoxic effects of DOXO in AML cells[3].
ln Vivo	The impairment in spatial memory is greatly improved by MPT0G211 (50 mg/kg; po; daily for 3 months)[1]. MPT0G211 (ip; qd; day 73 post-tumor injection; 25 mg/kg) decreases lung weights and nodule counts[2]. In addition to reducing tau phosphorylation by blocking GSK3β activity, MPT0G211 therapy increases Hsp90's acetylation, which downregulates HDAC6/Hsp90 binding and speeds up the proteasomal breakdown of polyubiquitinated p-tau[1].
Animal Protocol	Animal/Disease Models: Triple transgenic (3×Tg-AD) mice (harboring APPSwe and tauP301L mutant transgenes[1] Doses: 50 mg/kg Route of Administration: Po; daily for 3 months Experimental Results: Dramatically ameliorated the spatial memory impairment. Animal/Disease Models: Female SCID (severe combined immunodeficient) mouse (bearing MDA-MB-231 cells)[2] Doses: 25 mg/kg Route of Administration: Ip; qd; day 73 post-tumor injection Experimental Results: Dramatically diminished numbers of nodules and lung weights.
References	[1]. The novel histone de acetylase 6 inhibitor, MPT0G211, ameliorates tau phosphorylation and cognitive deficits in an Alzheimer's disease model. Cell Death Dis. 2018;9(6):655. Published 2018 May 29. [2]. Anti-metastatic activity of MPT0G211, a novel HDAC6 inhibitor, in human breast cancer cells in vitro and in vivo. Biochim Biophys Acta Mol Cell Res. 2019;1866(6):992-1003. [3]. The anticancer effects of MPT0G211, a novel HDAC6 inhibitor, combined with chemotherapeutic agents in human acute leukemia cells. Clin Epigenetics. 2018;10(1):162. Published 2018 Dec 29.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (340.92 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.4092 mL	17.0462 mL	34.0925 mL
	5 mM	0.6818 mL	3.4092 mL	6.8185 mL
	10 mM	0.3409 mL	1.7046 mL	3.4092 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.