571189-10-1Relevant articles and documents
Protection of renal tissues from ischemia through inhibition of the proliferative kinases CDK4 and CDK6
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, (2017/11/27)
The presently disclosed subject matter relates to methods and compositions for protecting cells and or tissues from damage due to ischemia. In particular, the presently disclosed subject matter relates to the protective action of cyclin dependent kinase 4/6 (CDK4/6) inhibitors administered to subjects that have been exposed to, or that are at risk of, ischemia.
CYCLIN DEPENDENT KINASE INHIBITORS AND METHODS OF USE
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, (2016/02/29)
The presently disclosed subject matter relates to methods and compositions for protecting healthy cells from damage due to DNA damaging agents. In particular, the presently disclosed subject matter relates to the protective action of selective cyclin dependent kinase 4/6 (CDK4/6) inhibitors administered to subjects that have been exposed to or that are at risk of exposure to DNA damage.
THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR AND/OR A CDK 4/6 INHIBITOR
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, (2016/02/29)
Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a Janus kinase-2 (JAK-2) inhibitor, a cyclin-dependent kinase- 4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.
SYNTHESIS OF 2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3-D]PYRIMIDIN-7-ONES
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Page/Page column 24, (2008/06/13)
The present invention provides methods of preparing substituted 2-(pyridin-2-ylamino)-pirido[2,3- d]pyrimidin-7-ones (formula 1 ), useful in treating cell proliferative disorders, or a pharmaceutically acceptable salt thereof.
Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6
Toogood, Peter L.,Harvey, Patricia J.,Repine, Joseph T.,Sheehan, Derek J.,VanderWel, Scott N.,Zhou, Hairong,Keller, Paul R.,McNamara, Dennis J.,Sherry, Debra,Zhu, Tong,Brodfuehrer, Joanne,Choi, Chung,Barvian, Mark R.,Fry, David W.
, p. 2388 - 2406 (2007/10/03)
A pharmacological approach to inhibition of cyclin-dependent kinases 4 and 6 (Cdk4/6) using highly selective small molecule inhibitors has the potential to provide novel cancer therapies for clinical use. Achieving high levels of selectivity for Cdk4/6, versus other ATP-dependent kinases, presents a significant challenge. The pyrido[2,3-d]pyrimidin-7-one template provides an effective platform for the inhibition of a broad cross-section of kinases, including Cdks. It is now demonstrated that the modification of pyrido[2,3-d]pyrimidin-7-ones to include a 2-aminopyridine side chain at the C2-position provides inhibitors with exquisite selectivity for Cdk4/6 in vitro. This selectivity profile is recapitulated in cells where the most selective inhibitors create a G1 block at concentrations up to 100-fold the IC50 for cell proliferation. On the basis of its selectivity profile and pharmacokinetic profile, compound 43 (PD 0332991) was identified as a drug candidate for the treatment of cancer.
ISETHIONATE SALT OF A SELECTIVE CDK4 INHIBITOR
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Page/Page column 21; 22, (2008/06/13)
Disclosed are polymorphs of the isethionate salt of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.
Combinations of signal transduction inhibitors
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Page/Page column 26, (2010/02/14)
The present invention relates to methods for treating cancer comprising utilizing a combination of signal transduction inhibitors. More specifically, the present invention relates to combinations of so called cell cycle inhibitors with mitogen stimulated kinase signal transduction inhibitors, more specifically combinations of CDK inhibitors with mitogen stimulated kinase signal transduction inhibitors, more preferably MEK inhibitors. Other embodiments of the invention relate to additional combinations of the aforesaid combinations with standard anti-cancer agents such as cytotoxic agents, palliatives and antiangiogenics. Most specifically this invention relates to combinations of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one including salt forms, which is a selective cyclin-dependent kinase 4 (CDK4) inhibitor, in combination with one or more MEK inhibitors, most preferably N-[(R)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide. The aforementioned combinations are useful for treating inflammation and cell proliferative diseases such as cancer and restenosis.
