RK-20449 is a pyrrolo-pyrimidine derivative HCK inhibitor.  Crystal structure analysis demonstrated that RK-20449 bound the activation pocket of HCK.  In vivo administration of Rk-20449 to non-obese (NOD)/severe combined immunodeficient (SCIS)/IL2rg(null) mice engrafted with aggressive therapy resistant AML, resulted in a significant reduction in human LSC and non-stem AML burden.  RK-20449 may eliminate chemotherapy resistant LSCs and prevent relapse, and thereby improve patient outcomes. HCK inhibition IC50 of 0.43 nM.

SMILE:  NC1=NC=NC2=C1C(C3=CC=C(OC4=CC=CC=C4)C=C3)=CN2[C@H]5CC[C@H](N6CCN(C)CC6)CC5 

Systematic Name: 7-((1r,4r)-4-(4-methylpiperazin-1-yl)cyclohexyl)-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 

Molecular Weight: 482.63 

Formula: C29H34N6O 

PMID: 23596204