TSCM-Ki Cocktail (T Memory Stem Cell Kinase Inhibitor Cocktail)

Cas No.:
Purity:	98%
Sotrage:	-80°C in DMSO
Publication:	Song, F., Tsahouridis, O., Stucchi, S., Walhart, T., Mendell, S., Hardy, P. B., Axtman, M., Guduru, S. K. R., Gilbert, T. S. K., Graves, L. M., Herring, L. E., Savoldo, B., Ma, X., Woodcock, M., Milner, J. J., Ivanova, A., Pearce, K. H., Xu, Y., & Dotti, G. (2025). A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells. Nature Immunology, 26, 279–293.

Description:

The TSCM-Ki Cocktail is a kinase inhibitor combination product validated through high-throughput screening. Its core function is to significantly increase the ratio of T memory stem cell (Tscm)-like cells—possessing self-renewal capacity and high persistence—in the final CAR-T cell product by transiently and reversibly modulating key kinase signaling pathways during the in vitroexpansion phase, thereby effectively preventing terminal T-cell differentiation. CAR-T cells manufactured using this product demonstrate superior tumor clearance capability and long-term immune memory in preclinical models.

References:

Song, F., Tsahouridis, O., Stucchi, S., Walhart, T., Mendell, S., Hardy, P. B., Axtman, M., Guduru, S. K. R., Gilbert, T. S. K., Graves, L. M., Herring, L. E., Savoldo, B., Ma, X., Woodcock, M., Milner, J. J., Ivanova, A., Pearce, K. H., Xu, Y., & Dotti, G. (2025). A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells. Nature Immunology, 26, 279–293.

Cat. No.	Product name	Field of application
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DC40169	DMG-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.
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
DC65786	DSPE-PEG2000-OH (DSPE-PEG hydroxyl)	DSPE-PEG2000-OH 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.
DC53130	93-O17S	93-O17S is an imidazole-based synthetic lipidoid for in vivo mRNA delivery. Lipid nanoparticles (LNPs) with 93-O17S promotes both the cross-presentation of tumor antigens and the intracellular delivery of cGAMP (STING agonist).