8WJY
PKMYT1_Cocrystal_Cpd 4
Summary for 8WJY
| Entry DOI | 10.2210/pdb8wjy/pdb |
| Descriptor | Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase, [6-azanyl-5-(2,6-dimethyl-3-oxidanyl-phenyl)-2,3-dimethyl-pyrrolo[2,3-b]pyrazin-7-yl]-(6,7-dihydro-4~{H}-pyrazolo[1,5-a]pyrazin-5-yl)methanone, DIMETHYL SULFOXIDE, ... (5 entities in total) |
| Functional Keywords | inhibitor, co-crystal, antitumor protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 35099.85 |
| Authors | |
| Primary citation | Wang, Y.,Wang, C.,Liu, T.,Qi, H.,Chen, S.,Cai, X.,Zhang, M.,Aliper, A.,Ren, F.,Ding, X.,Zhavoronkov, A. Discovery of Tetrahydropyrazolopyrazine Derivatives as Potent and Selective MYT1 Inhibitors for the Treatment of Cancer. J.Med.Chem., 67:420-432, 2024 Cited by PubMed Abstract: Breast and gynecological cancers are among the leading causes of death in women worldwide, illustrating the urgent need for innovative treatment options. We identified MYT1 as a promising new therapeutic target for breast and gynecological cancer using PandaOmics, an AI-driven target discovery platform. The synthetic lethal relationship of MYT1 in tumor cell lines with CCNE1 amplification enhanced this rationale. Through structure-based drug design, we developed a series of novel, potent, and highly selective inhibitors specifically targeting MYT1. Importantly, our lead compound, featuring a tetrahydropyrazolopyrazine ring, exhibits remarkable selectivity over WEE1, a related kinase associated with bone marrow suppression upon inhibition. Optimization of potency and physical properties resulted in the discovery of compound , a novel MYT1 inhibitor, exhibiting optimal pharmacokinetic properties and promising in vivo antitumor efficacy. PubMed: 38146659DOI: 10.1021/acs.jmedchem.3c01476 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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