63537-33-7

Basic information

• Product Name: 7H-Pyrazolo[3,4-d]pyridazin-7-one, 2,6-dihydro-3,4-dimethyl-2-(4-methylphenyl)-
• CAS NO: 63537-33-7
• Molecular Formula: C14H14N4O
• Molecular Weight: 254.291
• Mol File: 63537-33-7.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: 7H-Pyrazolo[3,4-d]pyridazin-7-one, 2,6-dihydro-3,4-dimethyl-2-(4-methylphenyl)-(CAS DataBase Reference)
• NIST Chemistry Reference: 7H-Pyrazolo[3,4-d]pyridazin-7-one, 2,6-dihydro-3,4-dimethyl-2-(4-methylphenyl)-(63537-33-7)
• EPA Substance Registry System: 7H-Pyrazolo[3,4-d]pyridazin-7-one, 2,6-dihydro-3,4-dimethyl-2-(4-methylphenyl)-(63537-33-7)

Safety Data

• Hazardous Substances Data: 63537-33-7(Hazardous Substances Data)

Upstream product

• 16382-10-8 ethyl 2-[2-(4-methylphenyl)hydrazinylidene]propanoate 
• 96723-37-4 4-acetyl-5-methyl-1-p-tolyl-1H-pyrazole-3-carboxylic acid 
• 128732-08-1 4-Acetyl-5-methyl-2,3-dioxo-2,3-dihydrofuran 
• 123-54-6 acetylacetone 
• 63514-80-7 ethyl 4-acetyl-5-methyl-1-(p-tolyl)-1H-pyrazole-3-carboxylate 

Downstream Products

• 723741-26-2 7-chloro-3,4-dimethyl-2-(p-tolyl)-2H-pyrazolo[3,4-d]pyridazine 

Relevant articles and documents

Discovery of Novel PDEδDegraders for the Treatment of KRAS Mutant Colorectal Cancer

KRAS-PDEδprotein-protein interaction represents an appealing target for cancer therapy. However, fast release of high-affinity inhibitors from PDEδhampered drug binding affinity and antiproliferative activity. To overcome the limitations, the first proteolysis-targeting chimeric (PROTAC) small molecules targeting PDEδwere designed. By employment of PDEδinhibitor deltazinone (2) and cereblon ligand pomalidomide (6), a series of potent PROTAC PDEδdegraders were obtained. The most promising compound 17f efficiently induced PDEδdegradation and demonstrated significantly improved antiproliferative potency in KRAS mutant SW480 cells. Compound 17f also achieved significant tumor growth inhibition in the SW480 colorectal cancer xenograft model. This proof-of-concept study provided a new strategy to validate the druggability of KRAS-PDEδinteraction and offered an effective lead compound for the treatment of KRAS mutant cancer.

Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site

The K-Ras GTPase is a major target in anticancer drug discovery. However, direct interference with signaling by K-Ras has not led to clinically useful drugs yet. Correct localization and signaling by farnesylated K-Ras is regulated by the prenyl binding protein PDEδ. Interfering with binding of PDEδ to K-Ras by means of small molecules provides a novel opportunity to suppress oncogenic signaling. Here we describe the identification and structure-guided development of novel K-Ras–PDEδ inhibitor chemotypes based on pyrrolopyridazinones and pyrazolopyridazinones that bind to the farnesyl binding pocket of PDEδ with low nanomolar affinity. We delineate the structure–property relationship and in vivo pharmacokinetic (PK) and toxicokinetic (Tox) studies for pyrazolopyridazinone-based K-Ras–PDEδ inhibitors. These findings may inspire novel drug discovery efforts aimed at the development of drugs targeting oncogenic Ras.