Structural interaction of Abemaciclib and CDK6

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(PDB # 5L2S used) Cyclin dependent kinase 6 (CDK6) works closely with cyclin D1 to regulate cell cycle progression. This makes CDK6 a perfect target for cancer treatment. However, most of the durgs designed to target CDK6 was not clinical significant. They either have extremely high cytotoxicity or low potency. Because CDK is very abundant and has such important function, it is very important to make the drug highly specfic to particular subfamily of CKD. Abeaciclib is one of the lastest generation (third generation) inhibitors for cyclin-dependent kinase 6. Unlike the first and second genereation drugs it is highly specific to CDK4/6 and has relative high potency. This model illustrated the contact area between abemaciclib and CDK6. It highlighted few special residues of CDK6 (His100, Asp104, Thr104) and the property of Abemaciclib molecule that contribute to its specific selectivity and affinity. And one residue (Lys43) that trying to balancing the selectivity and drug protency that worth to think about.