T807 |CAS 1415379-56-4|DC Chemicals

Cas No.:	1415379-56-4
Chemical Name:	5H-Pyrido(4,3-b)indole, 7-(6-fluoro-3-pyridinyl)-
Synonyms:	7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole;T 807;T-807;T807;FLORTAUCIPIR;J09QS3Z3WB;5H-Pyrido(4,3-b)indole, 7-(6-fluoro-3-pyridinyl)-;7-(6-Fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole;BCP24019;DB15033;AK686421;Q27280989
SMILES:	FC1C([H])=C([H])C(=C([H])N=1)C1C([H])=C([H])C2C3C([H])=NC([H])=C([H])C=3N([H])C=2C=1[H]
Formula:	C₁₆H₁₀FN₃
M.Wt:	263.2691
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	T807 a novel tau positron emission tomography (PET) tracer.
In Vivo:	[18F]T807 is able to cross the blood–brain barrier and ished out quickly in mice model. [18F]T807 clears rapidly from the brain, with activity values decreasing from 4.43% ID/g at 5 minutes to 0.62% ID/g at 30 minutes. Kidney elimination is a significant clearance pathway, resulting in a maximum tracer concentration of 14.99% ID/g in the kidneys at 5 minutes, which decreases to 5.52% ID/g at 30 minutes. The accumulation of activity in muscle and bone remain relatively low throughout the PET scan[1].
In Vitro:	Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD). In vitro autoradiography results show that [18F]T807 exhibits strong binding to PHF-tau positive human brain sections (Kd=14.6 nM). A comparison of autoradiography and double immunohistochemical staining of PHF-tau and Ab on adjacent sections demonstrates that [18F]T807 binding colocalizes with immunoreactive PHF-tau pathology, but does not highlight Ab plaques[1]. [18F]T807 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer’s brains e.g. intra and extraneuronal tangles and dystrophic neurites. [18F]T807 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions is identified[2].
Kinase Assay:	10 mg/mL frozen brain homogenate aliquots are thawed and diluted 10-fold in binding buffer to 1 mg/mL. 500 μL of appropriate concentrations of non-radioactive T807 to be tested are combined with 400 μL of [3H] T807 (29.7 Ci/mmol) in a volume of 900 μL of binding buffer. The assay begins by addition of 100 μL of the 1 mg/mL brain homogenate to achieve a final concentration of 0.10 mg tissue/mL for radioligands. The final concentration of [3H] T807 is typically 1-2 nM. After incubation at room temperature for 60 minutes, the binding mixture is filtered and rapidly washed 5 times with 3 mL binding buffer. The filters are counted[2].
Animal Administration:	Mice: Six male mice at each time point are administered 250 mCi [18F]T807 (in 200 mL saline) via tail vein injection. At 5, 15, and 30 minutes after administration, the mice are anesthetized and 500-mL whole blood samples and centrifuged. After euthanasia, the liver, kidneys, skeletal muscle (right quadriceps), brain, and bone (femur) are harvested and weighed. Each of the tissue samples are transferred to gamma counter tubes and counted[1].
References:	[1]. Xia CF, et al. [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013 Nov;9(6):666-76. [2]. Marquié M, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015 Nov;78(5):787-800.

MSDS

Cat. No.	Product name	Field of application
DC12145	DLinDMA	DLinDMA is a key lipid component of stable nucleic acid lipid particles as a benchmark.
DC40169	DMG-PEG2000(C14-PEG2000)	DMG-PEG 2000 is used for the preparation of liposome for siRNA delivery with improved transfection efficiency in vitro. DMG-PEG 2000 is also used for the lipid nanoparticle for an oral plasmid DNA delivery approach in vivo through a facile surface modific
DC45611	DMPC	1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a synthetic phospholipid used in liposomes. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine is used for the study of lipid monolayers and bilayers.
DC70000	Lysyllysyllysine	Lysyllysyllysine is a cationic moietie that may be used in the construction of gene delivery vectors and DNA nanoparticles.
DC33580	DODMA	DODMA, also known as MBN 305A is a a cationic lipid containing the unsaturated long-chain (18:1) oleic acid inserted at both the sn-1 and sn-2 positions. It has been used in the composition of lipospomes formulated as stable nucleic acid lipid particles that can encapsulate siRNA or other small molecules to be used for drug delivery
DC33635	DODAP	DODAP, also known as 1,2-Dioleoyl-3-dimethylammonium-propane, is a cationic lipid. It has been used as a component in liposomes that can be used to encapsulate siRNA, immunostimulatory oligodeoxynucleotides, antisense oligonucleotides, or chemotherapeutic agents for in vitro and in vivo delivery.
DC59010	C14-4 (C14-494,Lipid B-4,Lipid B4)	C14-4 (C14-494,Lipid B-4,Lipid B4) is a novel ionizable lipid with the highest T-cell transfection efficiency and low cytotoxicity.The C14-4 ionizable lipid has been explored for CAR-T therapy.To screen the excellent formulations for mRNA delivery, a lipid library of 24 ionizable lipids was constructed to make iLNPs, which were used to deliver luciferase mRNA into Jurkat cells.[115] The optimal iLNPs formulation was C14-4 iLNPs (C14-4 ionizable lipid, DOPE, chol, and PEG at a molar ratio of 35%, 16%, 46.5%, and 2.5%) (Figure 6c). The optimal dose of luciferase mRNA for C14-4 iLNPs was 30 ng. Compared with electroporated CAR T cells, the CAR T cells engineered via C14-4 iLNPs showed potent cancer-killing activity when they were cocultured with Nalm-6 acute lymphoblastic leukemia cells. To obtain a safer and more effective CAR mRNA delivery vehicle, the orthogonal design provided 256 potential formulations, and 16 representative iLNPs formulations were evaluated.Through evaluating the safety, delivery efficiency, and transfection efficiency of 16 iLNPs, the formulation B10 (C14-4 ionizable lipid, DOPE, chol, PEG at a molar ratio of 40%, 30%, 25%, and 2.5%) was screened out as the optimal performing formulation. The luciferase expression based on B10 formulation was increased threefold than the initial formulation. Reducing the accumulation and clearance of iLNPs in the liver can increase the expression of CAR mRNA in T cells, further improving the therapeutic effect of CAR-T. Studies have shown that cholesterol analogs can alter the mechanisms of intracellular circulation and enhance the delivery of mRNA, which may be related to the reduced recognition of iLNPs by the Niemann Pick C1 (NPC1) enzyme.The addition of a hydroxyl group to various locations in the cholesterol molecule can alter the binding kinetics between the modified cholesterol and NPC1, and reduced NPC1 recognition of cholesterol. The results showed that replacement of 25% and 50% 7 α-hydroxycholesterol for cholesterol in iLNPs improved mRNA delivery to primary human T cells in vitro by 1.8-fold and twofold, respectively.C14-4 is one of the ionizable lipids to efficiently deliver mRNA to Jurkat cells or primary human T cells. It will effectively promote the development of mRNA delivery by iLNPs for CAR-T therapy.
DC33636	DOTAP	DOTAP, also known as 1,2-Dioleoyl-3-trimethylammoniumpropane, is a cationic liposome-forming compound used for transfection of DNA, RNA, and other negatively charged molecules into eukaryotic cells. It has been used in gene delivery vectors for gene ther
DC58047	DSPE-PEG 2000	PEG2000-DSPE is used for creating micelles that are able to carry drugs with low solubility.
DC31000	LP-01	LP-01 is an ionizable cationic amino lipid (pKa = ~6.1). It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing LP-01 and encapsulating both Cas9 mRNA and modified single-guide RNA (sgRNA) for the transport protein transthyretin (Ttr) induce gene editing in liver cells in mice in a dose-dependent manner resulting in reduced serum Ttr levels for at least 12 months.