306-O12B-3 |Ionizable Lipid for LNP

Cas No.:	2982842-90-8
Chemical Name:	2-(Octyldisulfanyl)ethyl 3-[3-[3-[bis[3-[2-(octyldisulfanyl)ethoxy]-3-oxopropyl]amino]propyl-methylamino]propylamino]propanoate
Synonyms:	HY-137501;CS-0139522;PD166869;BP-29588;306-O12B-3;2982842-90-8;Bis(2-(octyldisulfaneyl)ethyl) 3,3'-((4-methyl-11-oxo-12-oxa-15,16-dithia-4,8-diazatetracosyl)azanediyl)dipropionate
SMILES:	S(CCCCCCCC)SCCOC(CCN(CCC(=O)OCCSSCCCCCCCC)CCCN(C)CCCNCCC(=O)OCCSSCCCCCCCC)=O
Formula:	C₄₆H₉₁N₃O₆S₆
M.Wt:	974.62
Purity:	>95%
Sotrage:	-20
Publication:	1. Yang, L., Ma, F., Liu, F., et al. Efficient delivery of antisense oligonucleotides using bioreducible lipid nanoparticles in vitro and in vivo. Mol. Ther. Nucleic Acids 19, 1357-1367 (2020). 2. Ma, F., Yang, L., Sun, Z., et al. Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection. Sci. Adv. 6(30), eabb4429 (2020).

Cat. No.	Product name	Field of application
DC67521	Lipid TD5	TD5 is a brain-targeting lipid nanoparticle (BLNP) engineered for efficient mRNA delivery to the central nervous system (CNS) via intrathecal injection. It incorporates a tryptamine-derived ionizable lipid headgroup, myristic acid hydrocarbon tails, and a biodegradable carbonate ester linker, enabling pH-dependent mRNA encapsulation (81.7% efficiency) and brain cell-specific targeting. With a hydrodynamic diameter of 107.5 nm, near-neutral pKa (7.30), and mild positive charge, TD 5 demonstrates superior CNS tropism through serotonin receptor (5-HT1A)-mediated endocytosis. In vitro, TD-5 achieved 80.8% GFP expression in SH-SY5Y neuronal cells, outperforming MC3 LNPs by 50-fold. Following intrathecal administration in mice, TD-5 mediated GFP expression in 29.6% of neurons and 38.1% of astrocytes brain-wide, with 10-fold higher CNS specificity than peripheral organs. Genome editing studies showed TD5-delivered Cas9/sgRNA induced tdTomato activation in ≈30% of neurons and 40% of astrocytes across key brain regions. Safety profiling revealed minimal systemic immune responses (lower IL-6, IL-12p40 vs MC3 LNPs), normal hepatic/renal biomarkers, and no histopathological toxicity. The optimized structure balances myristic chain hydrophobicity for membrane interaction, ionizable amines for mRNA complexation, and tryptamine-mediated targeting for enhanced CNS uptake, establishing TD5 as a promising platform for CNS gene therapies.
DC82025	306-O12B-3	306-O12B-3 is an ionizable lipidoid with cationic properties, commonly used in lipid nanoparticle (LNP) formulations for antisense oligonucleotide (ASO) delivery. When administered intravenously in mice, LNPs incorporating 306-O12B-3 exhibit liver-specific accumulation. Studies show that ASO-loaded LNPs containing 306-O12B-3 effectively silence hepatic PCSK9 expression by targeting the proprotein convertase subtilisin/kexin type 9 gene. Additionally, when combined with the cationic lipidoid NT1-O14B (Item No. 37095), these LNPs can deliver tau-targeting ASOs to the brain, reducing tau protein levels in mice.
DC60212	NT1-O14B	NT1-O14B is a tryptamine-containing cationic lipidoid.1 It has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs). Intravenous administration of LNPs containing NT1-O14B and encapsulating antisense nucleotides against tau decreases tau brain levels in mice.
DC41043	NT1-O12B	NT1-O12B, an endogenous chemical and a neurotransmitter-derived lipidoid (NT-lipidoid), is an effective carrier for enhanced brain delivery of several blood-brain barrier (BBB)-impermeable cargos. Doping NT1-O12B into BBB-impermeable lipid nanoparticles (LNPs) gives the LNPs the ability to cross the BBB. NT-lipidoids formulation not only facilitate cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination.