2019年7月1日 · Here, we describe a selective CDK7 inhibitor SY-1365, which is currently in clinical trials in populations of patients with ovarian and breast cancer (NCT03134638). In vitro, SY-1365 inhibited cell growth of many different cancer types at nanomolar concentrations. SY-1365 treatment decreased MCL1 protein levels, and cancer cells with low BCL2L1 ...

SY-1365, a CDK7 inhibitor has shown initial encouraging data in phase I for solid tumors treatment. These results have rejuvenated the CDKs research field. This review provides an overview of relevant advances on CDK inhibitor research since 2015 to 2019, with special emphasis on transcriptional CDK inhibitors, new emerging strategies such as ...

Mevociclib (SY-1365) is a potent and first-in-class selective CDK7 inhibitor, with a K i of 17.4 nM. Mevociclib exhibits anti-proliferative and apoptotic effects in solid tumor cell lines. Mevociclib possesses anti-tumor activity in hematological and multiple aggressive solid tumors

2017年7月1日 · SY-1365 was screened in a panel of solid tumor cell lines, revealing activity in breast, ovarian, colorectal and lung cancer cells with low nM EC 50 and rapid induction of apoptosis. In breast cancer, a subset of triple negative breast cancer (TNBC) cell lines were found to be more sensitive than luminal breast cancer cell lines, so we extended ...

2017年12月8日 · SY-1365, a selective inhibitor of CDK7, was developed to exploit tumor dependencies driven by CDK7 and is in clinical development in patients with advanced solid tumors. We have previously reported that SY-1365 selectively induces apoptosis in leukemic cells relative to non-malignant cells in vitro, and demonstrates anti-tumor activity in AML ...

New data on SY-1365, a first-in-class selective CDK7 inhibitor currently in a Phase 1 clinical trial, suggest that RB pathway alterations are predictive of response in preclinical models of high-grade ovarian cancer (HGOC) and support the ongoing clinical investigation of SY-1365 in patient populations enriched for RB pathway alterations.

2020年12月10日 · sy-1365通过下调致癌转录因子、抗凋亡蛋白(例如，mcl1和myc)、调控细胞周期与dna修复(尤其是，同源重组修复和错配修复)进展的通路来介导其抗癌活性，从而导致thp1细胞的凋亡 [52] 。值得注意的是，尽管靶标被完全占据，但在htert永生化的非癌细胞中观察到的凋亡 ...

SY-1365处理可降低MCL1蛋白水平，并且发现低BCL2L1（BCL-XL）表达的癌细胞对SY-1365更敏感。 急性髓细胞性白血病（AML）细胞系的转录变化与其他转录抑制剂处理后的变化不同。 SY-1365在多种AML异种移植模型中显示出显着的抗肿瘤作用。 SY-1365诱导的生长抑制与BCL2抑制剂Venetoclax结合使用可增强。 在卵巢癌异种移植模型中也观察到抗肿瘤活性，这表明在临床上探索SY-1365在血液学和实体瘤中的潜力。 我们的研究结果支持靶向CDK7作为治疗转录成瘾癌 …

Preclinical studies in solid tumor and hematologic malignancies show treatment with SY-1365 leads to antitumor activity, showing apoptosis in vitro and complete regressions in xenograft models. This first clinical study is focused on patients with advanced solid tumors.

SY-1365 Shows Synergistic Anti-Tumor Activity in Combination with Carboplatin in Preclinical Models of Ovarian Cancer, Supporting Ongoing Investigation of the Combination in Phase 1 Trial of SY-1365