942070-47-5Relevant articles and documents
Discovery of novel and orally bioavailable CDK 4/6 inhibitors with high kinome selectivity, low toxicity and long-acting stability for the treatment of multiple myeloma
Yuan, Kai,Kuang, Wenbin,Chen, Weijiao,Ji, Minghui,Min, Wenjian,Zhu, Yasheng,Hou, Yi,Wang, Xiao,Li, Jiaxing,Wang, Liping,Yang, Peng
, (2021/12/09)
Multiple myeloma (MM) ranks second in malignant hematopoietic cancers, and the most common anti-MM drugs easily generate resistance. CDK4/6 have been validated to play determinant roles in MM, but no remarkable progress has been obtained from clinical trials of CDK4/6 inhibitors for MM. To discover novel CDK6 inhibitors with better potency and high druggability, structure-based virtual screening was conducted to identify compound 10. Further chemical optimization afforded a better derivative, compound 32, which exhibited strong inhibition of CDK4/6 and showed high selectivity over 360+ kinases, including homologous CDKs. The in vivo evaluation demonstrated that compound 32 possessed low toxicity (LD50 > 10,000 mg/kg), favorable bioavailability (F% = 51%), high metabolic stability (t1/2 > 24 h) and strong anti-MM potency. In summary, we discovered a novel CDK4/6 inhibitor bearing favorable drug-like properties and offered a great candidate for MM preclinical studies.
Five-membered heterocyclic oxo carboxylic acid compound and medical application thereof
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Paragraph 0655-0659, (2021/05/01)
The invention relates to a five-membered heterocyclic oxo carboxylic acid compound and a medical application thereof. Specifically, the invention relates to a compound, a pharmaceutical salt, a prodrug, a hydrate, a solvate or a crystal form as shown in a formula (I), and also relates to a preparation method of the compound, a pharmaceutical composition containing the compound and an application of the pharmaceutical composition as a secretion regulator of interferon type I, especially as an STING agonist in preparation of medicines for preventing and/or treating I-type interferon related diseases.
TYK2 INHIBITORS AND USES THEREOF
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, (2020/05/14)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.