839708-52-0

Upstream product

• 839708-51-9 N-{3-[(2-chloro-4-methylaminopyrimidin-5-ylmethyl)amino]-4-methylphenyl}-3-trifluoromethylbenzamide 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 2251-65-2 3-(Trifluoromethyl)benzoyl chloride 
• 7627-38-5 2,4-dichloro-5-(chloromethyl)pyrimidine 
• 4433-40-3 5-(hydroxymethyl)pyrimidine-2,4-diol 
• 205672-24-8 5-bromo-2-chloro-N-methyl-pyrimidin-4-amine 
• 839708-49-5 (2-chloro-5-vinylpyrimidin-4-yl)methylamine 
• 839708-50-8 2-chloro-4-(methylamino)pyrimidine-5-carbaldehyde 

Downstream Products

• 839706-07-9 GNF-7 
• 839708-13-3 GNF-8 
• 839708-29-1 GNF-6 
• 839707-37-8 N-(3-(7-((1,3-dimethyl-1H-pyrazol-5-yl)amino)-1-methyl-2-oxo-1,4-dihydropyrimido[4,5-d]pyrimidin-3(2H)-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide 

Relevant academic research and scientific papers

First SAR Study for Overriding NRAS Mutant Driven Acute Myeloid Leukemia

GNF-7, a multitargeted kinase inhibitor, served as a dual kinase inhibitor of ACK1 and GCK, which provided a novel therapeutic strategy for overriding AML expressing NRAS mutation. This SAR study with GNF-7 derivatives, designed to target NRAS mutant-driven AML, led to identification of the extremely potent inhibitors, 10d, 10g, and 11i, which possess single-digit nanomolar inhibitory activity against both ACK1 and GCK. These substances strongly suppress proliferation of mutant NRAS expressing AML cells via apoptosis and AKT/mTOR signaling blockade. Compound 11i is superior to GNF-7 in terms of kinase inhibitory activity, cellular activity, and differential cytotoxicity. Moreover, 10k possessing a favorable mouse pharmacokinetic profile prolonged life-span of Ba/F3-NRAS-G12D injected mice and significantly delayed tumor growth of OCI-AML3 xenograft model without causing the prominent level of toxicity found with GNF-7. Taken together, this study provides insight into the design of novel ACK1 and GCK dual inhibitors for overriding NRAS mutant-driven AML.

THERAPEUTIC AGENT OF ACUTE MYELOID LEUKEMIA CONTAINING 1,3,7-TRISUBSTITUTED 3,4-DIHYDROPYRIMIDO[4,5-D]PYRIMIDINE-2(1H)-ONE DERIVATIVES

The present invention provides a therapeutic agent of acute myeloid leukemia containing a 1,3,7-trisubstituted 3,4-dihydropyrimido[4,5-d]pyrimidine-2(1H)-one compound as an active ingredient, which has proliferation inhibitory activity for a human acute myeloid leukemia cell line OCI-AML3 having a NRAS mutant gene while having low inhibitory activity for wild type NRAS and has activity of inhibiting GCK and ACK1 protein kinases at the same time.

COMPOUNDS THAT MAINTAIN PLURIPOTENCY OF EMBRYONIC STEM CELLS

The present invention relates to methods and compositions for culturing embryonic stem (ES) cells. The methods relate to growing the ES cells in the presence of small molecules of formula (I) that maintain the pluripotency/self-renewal of the cells withou