HDAC-IN-57 |CAS 2716217-79-5|DC Chemicals

Cas No.:	2716217-79-5
Chemical Name:	HDAC-IN-57
SMILES:	COC1=CC=C(C2=NC=CC(C(NCC3=CC=C(C(NO)=O)C=C3)=O)=C2)C=C1
Formula:	C₂₁H₁₉N₃O₄
M.Wt:	377.4
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	HDAC-IN-57 is an orally active inhibitor of histone deacetylases (HDAC), with IC50s of 2.07 nM, 4.71 nM, 2.4 nM and 107 nM for HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-57 can inhibits LSD1, with IC50 of 1.34 μΜ. HDAC-IN-57 induces apoptosis, and has anti-tumor activity[1].
Target:	HDAC1:2.07 nM (IC50) HDAC2:4.71 nM (IC50) HDAC6:2.4 nM (IC50) HDAC8:107 nM (IC50)
In Vivo:	HDAC-IN-57 (Compound 5e) (静脉注射1 mg/kg，口服10 mg/kg) 显示 T＜sub＞1/2HDAC-IN-57 (25或50 mg/kg灌胃；每天1次，连续21天) 在 NOD-SCID 小鼠 MGC-803 异种移植模型中实现了剂量依赖性肿瘤生长抑制[1]。 Animal Model: MGC-803 xenograft model in NOD-SCID mice[1] Dosage: 25 or 50 mg/ kg Administration: Oral gavage (p.o.); Result: Achieved a dose-dependent tumor growth inhibition (TGI) of 44.8% at 25 mg/kg and 71.5% at 50 mg/kg. Animal Model: Male SD rats (Pharmacokinetic assay)[1] Dosage: 1 mg/kg; 10 mg/kg Administration: Intravenous injection (i.v.); Oral gavage (p.o.) Result: Pharmacokinetic parameters for HDAC-IN-57 (Compound 5e) in SD rats[1] Route Dose (mg/kg) T1/2 (h) Tmax (h) CL (mL•min-1/kg-1) AUC0-t (h•ng/mL) AUC0-Ꝏ (h•ng/mL) Cmax (ng/mL) VZ (L/kg) F (%) i.v. 1 0.37 / 1.61 644.1 645.8 1892.8 0.82 / p.o. 10 2.75 0.25 / 685.2 766.2 716.4 52.2 10.6 分子量 377.39 Formula C21H19N3O4 CAS 号 2716217-79-5 运输条件 Room temperature in continental US; may vary elsewhere. 储存方式 Please store the product under the recommended conditions in the Certificate of Analysis. 纯度 & 产品资料 Data Sheet (535 KB) 产品使用指南 (1538 KB) 参考文献 [1].
In Vitro:	HDAC-IN-57 (Compound 5e) (1.0 μM，2.5 μM，5.0 μΜ； 48 小时) 抑制实体肿瘤细胞系 MGC-803，A549，HCT-116 的迁移和侵袭[1]。 HDAC-IN-57 (1.0 μM，2.5 μM，5.0 μΜ；48小时) 显著抑制实体肿瘤细胞系 MGC-803，A549，HCT-116 的生长，IC50s 值分别为 0.45 μM, 1.48 μM 和 0.57 μM[1]。 HDAC-IN-57 (1.0 μM，2.5 μM，5.0 μΜ；48小时) 以剂量依赖性方式触发 MGC-803 和 HCT-116 细胞凋亡[1]。 HDAC-IN-57 (1.0 μM，2.5 μM，5.0 μΜ；48小时) 抑制 MGC-803 和 HCT-116 细胞系内 LSD1 和 HDACs[1]。 HDAC-IN-57 (1.0 μM，2.5 μM，5.0 μΜ；48小时) 诱导 MGC-803 和 HCT-116 细胞周期 G2/M 期阻滞[1]。 HDAC-IN-57 在体外代谢稳定性高。在人肝脏 (HLM) 和大鼠肝脏微粒体 (RLM) 中孵育1 小时后分别保持母体化合物的 86.1% 和 87.4%，T1/2超过 120 分钟[1]。 Western Blot Analysis[1] Cell Line: MGC-803 cells, HCT-116 cells Concentration: 1.5 μM Incubation Time: 48 hours Result: Inhibited cellular LSD1 and HDACs. Upregulated the expression of apoptotic markers, including cytochrome C, Bax, cleaved caspase-3/7/9, and cleaved PARP, while downregulating the expression of anti-apoptotic protein Bcl-2. Apoptosis Analysis[1] Cell Line: MGC-803 cells, HCT-116 cells Concentration: 1.0 μM, 2.5 μM, 5.0 μM Incubation Time: 48 hours Result: Triggered MGC-803 and HCT116 cells apoptosis in a dose-dependent manner. Induced about 55.4% and 51.5% MGC-803 cell apoptosis at a concentration of 5 μM. Cell Migration Assay [1] Cell Line: MGC-803 cells, HCT-116 cells Concentration: 1.0 μM, 2.0 μM, 4 μM Incubation Time: 48 hours Result: Reduced the number of migrated of MGC-803 and HCT-116 cells. Inhibited the migration and invasion of cancer cells. Cell Cycle Analysis[1] Cell Line: MGC-803 cells, HCT-116 cells Concentration: 1.0 μM, 2.5 μM, 5.0 μM Incubation Time: 48 hours Result: Induced G2/M cycle arrest in MGC-803 and HCT-116 cells.
References:	[1]. Duan Y, et al. Discovery of novel, potent, and orally bioavailable HDACs inhibitors with LSD1 inhibitory activity for the treatment of solid tumors. Eur J Med Chem. 2023 Jun 5;254:115367.

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.