Cantuzumab mertansine |CAS 400010-39-1|DC Chemicals

Cas No.:	400010-39-1
Chemical Name:	Immunoglobulin G1,anti-(mucin CanAg) (human-mouse monoclonal C242 heavy chain), disulfide withhuman-mouse monoclonal C242 light chain, dimer, tetraamide withN2'-[3-[(3-carboxy-1-methylpropyl)dithio]-1-oxopropyl]-N2'-deacetylmaytansine
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Cantuzumab mertansine (SB-408075; huC242-DM1), an ADC, is an immunoconjugate of the potent maytansine derivative (DM1; HY-19792) and the humanized monoclonal antibody (huC242) directed to CanAg. Cantuzumab mertansine has cytotoxic toward colon cancer cells and has broad antitumor efficacy against a range of CanAg-positive human tumor xenografts[1][2].
In Vivo:	Cantuzumab mertansine (SB-408075; huC242-DM1; 300 μg/kg/day for 5 days) resultes in complete regressions and cures of mice bearing human xenografts of Colo 205 colon cancer[1]. Animal Model: Female CB-17 SCID mice, 6-7 weeks of age bearing COLO 205 human colon tumor xenografts[1] Dosage: 300 μg/kg Administration: Daily for 5 days Result: Completely eliminated any measurable tumors within 2 weeks of the initiation of therapy, and all eight animals were tumor-free for 200 days (duration of the experiment).
In Vitro:	Cantuzumab mertansine (SB-408075; huC242-DM1; 0-100 μM; 24 h) has selective cytotoxic activity on antigen-positive COLO 205 cell line[1]. Cell Cytotoxicity Assay[1] Cell Line: Antigen-positive COLO 205 cell line and the antigen-negative A-375 melanoma cell line Concentration: 0-100 μM Incubation Time: 24 h Result: Had cytotoxic activity on COLO 205 cells with an IC50 value of 0.032 nM (23.5 pg/ml). Had 1100-fold less cytotoxic activity for the antigen-negative A-375 cells (IC50=36 nM; 26.5 ng/ml).
References:	[1]. Paul R Helft, et al. A phase I study of cantuzumab mertansine administered as a single intravenous infusion once weekly in patients with advanced solid tumors. Clin Cancer Res. 2004 Jul 1;10(13):4363-8. [2]. Anthony W. Tolcher, et al. Cantuzumab Mertansine, a Maytansinoid Immunoconjugate Directed to the CanAg Antigen: A Phase I, Pharmacokinetic, and Biologic Correlative Study. J Clin Oncol. 2003 Jan 15;21(2):211-22.

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.