1429882-07-4

Usage

Uses

Used in Pharmaceutical Industry:
UNC-2371A is used as a therapeutic agent for targeting specific protein kinases, such as MERTK and FLT3. It inhibits Mer and FMS-like tyrosine kinase 3 (FLT3) with IC50s of 1.3 and 1 nM, respectively, and also inhibits Axl and Tyro3 with IC50s of 15 and 17 nM, respectively. UNC-2371A has demonstrated its effectiveness in inhibiting Mer phosphorylation in MOLM-14 and MV4-11 acute myeloid leukemia (AML) cells and reducing clonal expansion of Kasumi-1 AML cells (IC50 = 143.5 nM).
Used in Drug Delivery Systems:
In the field of drug delivery, UNC-2371A can be utilized to enhance the bioavailability and therapeutic outcomes of various drugs. By employing different carriers, such as organic and metallic nanoparticles, UNC-2371A can be delivered more effectively to target cancer cells, improving its overall efficacy and potentially overcoming limitations associated with its use.

Upstream product

• 89381-08-8 2-Cyclopropylethylamine hydrochloride 
• 1630906-40-9 trans-4-(5-bromo-2-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexan-1-ol 
• 938043-30-2 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)piperazine 

Relevant academic research and scientific papers

POLYMORPHS OF A KINASE INHIBITOR, PHARMACEUTICAL COMPOSITIONS CONTAINING SUCH A COMPOUND, PREPARATION METHODS, AND APPLICATIONS

The invention relates to new crystal forms of compound (trans)-4-((2- cyclopropylethyl)amino)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-7H- pyrrolo[2,3-d]pyrimidin-7-yl) cyclohexanol trihydrochloride, its hydrate, or solvate, as shown in the formula. The invention also relates to methods for preparation of the described compound, crystal form, and related intermediate compounds, as well as pharmaceutical compositions containing the compounds. Further described is, the use of the compounds or crystal forms in the production of a medicament for the treatment of a disease, symptom, or condition, or the use in treatment of a disease, symptom or condition.

UNC2025, a potent and orally bioavailable MER/FLT3 dual inhibitor

We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer in leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300 kinases in vitro and cellular selectivity assessments demonstrate that 11 has similar subnanomolar activity against Flt3, an additional important target in acute myelogenous leukemia (AML), with pharmacologically useful selectivity versus other kinases examined.