Mar 23, 2022 · KRLS-017 is a reversible small molecule inhibitor of Cyclin Dependent Kinase 7 (CDK7). CDK7 has been implicated as a key regulator of both transcriptional addiction and cell cycle dysregulation in tumors and therefore represents an attractive target for therapeutic intervention across a broad range of solid tumors and hematologic malignancies.

Mar 23, 2022 · KRLS-017は、可逆的Cyclin Dependent Kinase 7（CDK7）選択的阻害薬（低分子化合物）です。 CDK7は、腫瘍における転写依存と細胞周期調節異常の両方の重要な調節因子として関与しているため、広範囲の固形腫瘍および血液悪性腫瘍に対する治療的介入の魅力的な標的となります。 KRLS-017は、前臨床試験でクラス最高の効力、選択性、および抗腫瘍効果に加えて、経口薬として非常に好ましい特性を示しているため、抗腫瘍薬としてアンメットメ …

Mar 23, 2022 · KRLS-017は、可逆的Cyclin Dependent Kinase 7 (CDK7) 選択的阻害薬（低分子化合物）です。 CDK7は、腫瘍における転写依存と細胞周期調節異常の両方の重要な調節因子として関与しているため、広範囲の固形腫瘍および血液悪性腫瘍に対する治療的介入の魅力的な標的 …

Cyclin dependent kinase 7 (CDK7) is an attractive target for cancer drugs due to its dual roles, cell cycle regulation and gene transcription/RNA procession. Recent studies show that transcription of some oncogene is highly sensitive to inhibition of transcription such as inhibition by CDK7.

Kirilys’ lead asset is KRLS-017, a selective and potent Cyclin Dependent Kinase 7 (“CDK7”) inhibitor for multiple oncology indications, in-licensed from UBE. CDK7 has been implicated as a key regulator of both transcriptional addiction and cell cycle dysregulation in tumors and therefore represents an attractive target for therapeutic ...

Apr 10, 2023 · CDK7 is a promising therapeutic target for the treatment of cancer. Small molecule inhibitors with various mechanisms of action are exploited, including ATP competitors, covalent binders and PROTACs. Selective CDK7 inhibitors have …

May 30, 2017 · We synthesized a novel highly selective CDK7 inhibitor, UD-017, and found that the compound showed antitumor potency in a variety of cancers in vitro and in vivo. We therefore explored underlying mechanisms especially focusing on an oncogenic driver, c-Myc. Methods: We examined CDK7 selectivity of UD-017 against the other CDKs and kinases.

Results: UD-017 significantly inhibited CDK7 activity (IC 50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI 50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling.

KRLS-017 was in-licensed from UBE Corporation, a premier Japanese chemical manufacturer, and has demonstrated best-in-class selectivity and drug-like properties in preclinical models. It is being developed with insights from a proprietary biomarker platform via …

May 30, 2017 · In this study, we characterize antitumor activity of UD-017 in vitro and in vivo, and try to elucidate underlying mechanisms by which CDK7 inhibition contributes to the antitumor efficacy in colorectal cancer cells. Methods: We examined CDK7 selectivity of UD-017 against the other CDKs and kinases. We evaluated the antitumor activity in a ...