5054-59-1

Basic information

• Product Name: 4-Hydroxy ThalidoMide
• Synonyms: 4-Hydroxy ThalidoMide;2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione;2-(2,6-Dioxo-piperidin-3-yl)-4-hydroxy-isoindole-1,3-dione;2-(2,6-dioxopiperidin-3-yl)-4-hydroxy-2,3-dihydro-1H-isoindole-1,3-dione;E3 ligase Ligand 2
• CAS NO: 5054-59-1
• Molecular Formula: C₁₃H₁₀N₂O₅
• Molecular Weight: 274.2289
• Mol File: 5054-59-1.mol
• Article Data: 17

Chemical Properties

• Melting Point: 273-275 °C
• Boiling Point: 568.3±45.0 °C(Predicted)
• Appearance: /
• Density: 1.611±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 6.82±0.20(Predicted)
• CAS DataBase Reference: 4-Hydroxy ThalidoMide(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Hydroxy ThalidoMide(5054-59-1)
• EPA Substance Registry System: 4-Hydroxy ThalidoMide(5054-59-1)

Safety Data

• Hazardous Substances Data: 5054-59-1(Hazardous Substances Data)

Usage

Description

4-Hydroxy ThalidoMide is a Thalidomide-based Cereblon ligand that is utilized for the recruitment of CRBN protein. It can be connected to the ligand for protein by a linker to form PROTACs, which are a new class of therapeutic agents that can modulate protein levels in cells.

Uses

Used in Cancer Research:
4-Hydroxy ThalidoMide is used as an intermediate for the synthesis of dTAG-13 (D710020), which is a degradation tag that has been tested for its efficiency at depleting FKBP12F36V-MELK(sg3R). It has been found to significantly degrade FKBP12F36V-MELK(sg3R) within 4 hours, making it a valuable tool in the study of cancer research.
Used in Drug Development:
4-Hydroxy ThalidoMide is used as a key component in the development of PROTACs, which are a promising new class of therapeutic agents that can modulate protein levels in cells. These agents have the potential to target a wide range of diseases, including cancer, by selectively degrading disease-causing proteins.
Used in Pharmaceutical Industry:
4-Hydroxy ThalidoMide is used as a starting material for the synthesis of various pharmaceutical compounds, including dTAG-13 (D710020). Its unique properties make it a valuable asset in the development of new drugs and therapies for a variety of medical conditions.
Used in Chemical Research:
4-Hydroxy ThalidoMide is used as a research compound in the field of chemical research, where it can be studied for its properties and potential applications in various chemical reactions and processes. Its unique structure and reactivity make it an interesting subject for further investigation and development.

Upstream product

• 27550-59-0 4-hydroxyphthalic anhydride 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 37418-88-5 3-hydroxyphthalic anhydride 
• 2353-44-8 (+/-)-α-aminoglutarimide 

Downstream Products

• 1799711-25-3 N-(4-aminobutyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide trifluoroacetate salt 

Relevant articles and documents

Preparation of targeted GSK3 alpha/beta degradation agent and medical application thereof

The invention discloses preparation of a targeted GSK3 alpha/beta degradation agent and a medical application thereof. The pharmaceutical composition comprises compounds or pharmaceutically acceptable salts thereof as shown in general formulas (I) and (II), R is selected from Cl and I, m is selected from 2, 3, 4, 5 and 6, and n is selected from 1, 2 and 4. The invention provides the degradation agent, and the compound disclosed by the invention can effectively degrade cell GSK3 alpha/beta in a targeting manner, and can be used as a therapeutic agent for Alzheimer's disease or other GSK3 protein related diseases.

Proteolysis targeting chimera and application thereof

The invention provides a proteolysis targeting chimera and application thereof. According to a technical scheme in the invention, a novel PROTAC degradation agent compound 21a is developed on the basis of a BMS-37 small molecule. The novel PROTAC degradation agent compound 21a is an example of degrading membrane proteins on the basis of a ligand binding to the extracellular domain of a PD-L1 protein, and can effectively degrade PD-L1 in various malignant tumor cells. In-vivo research results show that after treatment with the compound 21a, the compound 21a can significantly reduce the level of the PD-L1 in tumors, promote infiltration of CD8T cells and significantly inhibit growth of mouse colorectal cancer MC-38 cells. The PROTAC molecule is expected to be one of novel and alternative strategies for cancer immunotherapy.

In vitro and in vivo degradation of programmed cell death ligand 1 (PD-L1) by a proteolysis targeting chimera (PROTAC)

Immunotherapy via immune checkpoints blockade has aroused the attention of researchers worldwide. Inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction has been one of the most promising immunotherapy strategies. Several neutralizing antibodies targeting this interaction have been developed, which have already achieved considerable clinical success. Additionally, numerous pharmaceutical companies have been committed to develop small molecules which could block the interaction between PD-1 and PD-L1. In this study, a novel PROTAC molecule 21a was developed, and effectively induced the degradation of PD-L1 protein in various malignant cells in a proteasome-dependent manner. Moreover, compound 21a could significantly reduce PD-L1 protein levels of MC-38 cancer cells in vivo, by which promoted the invasion of CD8+ T cells and inhibited the growth of MC-38 in vivo. This PROTAC molecule could be used as a novel and alternative strategy for cancer immunotherapy.