CDK1 Inhibitor

Dimethyl bisphenolate (Compound DMB) is a natural neolignan derivative with orally active anti-tumor activity. Dimethyl bisphenolate can inhibit cancer cells proliferation, invasion and migration. Dimethyl bisphenolate can activate the p53 signaling pathway, upregulate the expression of p21 protein, inhibit the activity of the CDK1-cyclin B1 complex, and cause cells to stall at the G2/M phase. Dimethyl bisphenolate can induce ROS production, upregulate pro-apoptotic proteins Noxa and Bim, downregulate anti-apoptotic protein Bcl-2, activate caspase-9 and caspase-3, and ultimately induce cell apoptosis. Dimethyl bisphenolate can be used for research of glioblastoma.

PI3Kα-IN-33 is an orally active and selective PI3Kα inhibitor with an IC₅₀ of 9.9 nM. PI3Kα-IN-33 blocks the PI3K/Akt/mTOR signaling pathway. PI3Kα-IN-33 induces apoptosis and triggers G2/M-phase arrest via Cyclin B1 and CDK1 downregulation. PI3Kα-IN-33 can be used for the research of colorectal cancer.

CDK1/2/4-IN-1 (compound 3a) is a potent CDK inhibitor with IC₅₀ values of 1.47, 0.78 and 0.87 μM for CDK1, CDK2 and CDK4, respectively. CDK1/2/4-IN-1 arrests cell cycle at G2/M phase and induces apoptosis. CDK1/2/4-IN-1 elevates Bax, caspase-3, P53 levels and decreases Bcl-2 level. CDK1/2/4-IN-1 can be used for cancer research.

CIRc-014 is an orally active Cyclin A/B inhibitor with a Cyclin A IC₅₀ of 0.05 μM, Cyclin A K_d of 2.7 nM, Cyclin B IC₅₀ of less than 0.02 μM and Cyclin B K_d of 1.0 nM. CIRc-014 activates the spindle assembly checkpoint and promotes the formation of a complex between Cyclin B and CDK2 by blocking the RxL interaction of Cyclin A/B. CIRc-014 can induce replication stress, DNA damage, mitotic arrest and apoptosis in tumor cells. CIRc-014 showed tumor growth inhibition and regression in NCI-H69 and NCI-H446 small cell lung cancer xenograft models. CIRc-014 can be used for the research of small-cell lung cancer.

Antitumor agent-174 (Compound 10) directly engages the N-terminal site of Hsp90 and promotes the degradation of β-catenin, thereby suppressing the Wnt/β-catenin signaling. Antitumor agent-174 effectively inhibits proliferation, induce S and G2/M phases arrest and block the clonogenic ability in CRC cells. Antitumor agent-174 down-regulates CDK1, Cyclin D1, c-Myc, Cyclin B1, and Cyclin A2, and upregulaties P21 proteins. Antitumor agent-174 has significant anti-tumor efficacy against colorectal cancer (CRC) with excellent pharmacokinetics and low toxicity.

PKMYT1-IN-15 is an orally active PKMYT1 inhibitor with an IC₅₀ of 6.02 nM. PKMYT1-IN-15 inhibits the phosphorylation of CDK1 at Thr14. As an antiproliferative agent, DNA damage inducer and antitumor agent, PKMYT1-IN-15 triggers replication-associated DNA damage and cell death in CCNE1-amplified cancer cells, and suppresses tumor growth in the OVCAR3 xenograft model. PKMYT1-IN-15 can be used for the research of CCNE1-amplified cancers (e.g., ovarian cancer, breast cancer).

CGP-74514 hydrochloride is a highly selective cyclin-dependent kinase 1 (CDK1) inhibitor (IC₅₀: 25 nM). CGP-74514 hydrochloride inhibits CDK1/cyclin B complex activity, arrests the cell cycle at G₂/M phase and induces tumor cell apoptosis. CGP-74514 hydrochloride is promising for research of bladder cancer.

Anticancer agent 29 (Compd E/Z-6f) is an anticancer agent, with IC₅₀ values of 0.054 μM, 0.127 μM, 0.129 μM, 0.396 μM for CDK2, CDK1, CDK4 and CDK6, respectively.

GIT1-IN-1 is an inhibitor of ARF GTPase-activating protein 1 (GIT1) with a K_D of 6.2 μM. GIT1-IN-1 induces apoptosis (apoptosis) in liver and colon cancer cells, arrests the cell cycle at the G2/M phase, and inhibits cell proliferation, colony formation and migration. GIT1-IN-1 inhibits the activities of MEK and ERK, reduces the expression level of cyclin D1, and stabilizes cyclin B1 protein in liver and colon cancer cells. GIT1-IN-1 can be used in the research of liver cancer and colon cancer.

Anticancer agent 264 (Compound 5w) is an anticancer agent that exhibits significant antiproliferative activity across tumor cell lines, with an IC₅₀ range of 7.5-33.67 μM. Anticancer agent 264 significantly induces G2/M phase arrest in MDA-MB-231, MIA PaCa-2, and DU-145 cell lines. Anticancer agent 264 reduces the expression of key cell cycle proteins, including CDK1, CDK2, and Cyclin B1, in a dose-dependent manner, and shows strong binding affinity with inhibitor of differentiation (ID) proteins and DNA-binding proteins. Anticancer agent 264 can be used for research in the field of cancer-related diseases.

WEE1/PKMYT1-IN-4 is a selective WEE1/PKMYT1 inhibitor, with IC₅₀ values of 0.185 μM and 2.2 nM for human WEE1 and PKMYT1, respectively. WEE1/PKMYT1-IN-4 inhibits phosphorylation of CDK1 at T14 and Y15, disrupting the G2/M cell cycle checkpoint. WEE1/PKMYT1-IN-4 can be used for the research of colorectal cancer and amplified breast cancer.

UNPD139734 is a CDK-1 inhibitor and PARP-1 inhibitor that forms stable complexes with each target protein. UNPD139734 serves as a lead compound for structural optimization to develop dual-target anticancer agents targeting CDK-1 and PARP-1. UNPD139734 can be used for the research of breast cancer.

AG-12286 is a pan-CDK inhibitor with an IC₅₀ value of 2 nM against cdk1/cyclin B, 6 nM against cdk2/cyclin E, and 12 nM against cdk4/cyclin D. AG-12286 is 1000-fold more selective for the CDK family than for PKC. AG-12286 can be used in cancer research.

CGP-74514 dihydrochloride is a highly selective cyclin-dependent kinase 1 (CDK1) inhibitor (IC₅₀=25 nM). CGP-74514 dihydrochloride inhibits CDK1/cyclin B complex activity, arrests the cell cycle at G₂/M phase and induces tumor cell apoptosis. CGP-74514 dihydrochloride is promising for research of bladder cancer.

PKMYT1-IN-13 is a potent, orally active and selective PKMYT1 inhibitor that inhibits PKMYT1 with IC₅₀ values < 10.0 nM in ADP-Glo assay and 19.9 nM in NanoBRET cellular assay. PKMYT1-IN-13 exhibits high selectivity over WEE1. PKMYT1-IN-13 shows selective antiproliferative activity in CCNE1-amplified cells, while showing minimal wild-type effects. PKMYT1-IN-13 shows antitumor efficacy in HCC1569 mouse xenografts. PKMYT1-IN-13 can be used for the research of CCNE1-amplified cancers, such as gastric, ovarian, and breast cancer.

Indirubin-3'-monoxime-5-sulphonic acid is a potent and selective inhibitor of CDK1, CDK5, and GSK-3β with IC₅₀s of 5 nM, 7 nM, and 80 nM, respectively.

Aloisine RP106 (compound 38) is a potent inhibitor of Cdk1/cyclin B, Cdk5/p25, and GSK3 with IC₅₀s of 0.70µM, 1.5µM, 0.92 µM, respectively.

PARP1-IN-50 is a selective and orally active PARP-1 inhibitor with an IC₅₀ of 64.98 nM. PARP1-IN-50 can inhibit PAR formation and induce DNA double strand breaks, thereby causing DNA damage. PARP1-IN-50 can induce G2/M phase arrest and cancer cells apoptosis. PARP1-IN-50 demonstrates significant antiproliferative activity against various cancer cells. PARP1-IN-50 can be used for the research of cancer, such as breast cancer.

Indirubin-5-sulfonate is a cyclin-dependent kinase (CDK) inhibitor, with IC₅₀ values of 55 nM, 35 nM, 150 nM, 300 nM and 65 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK4/cyclin D1, and CDK5/p35, respectively. Indirubin-5-sulfonate also shows inhibitory activity against GSK-3β.

CDK1-IN-9 is an orally active and selective CDK1 inhibitor with an IC₅₀ of 5.5 nM. CDK1-IN-9 exhibits broad antiproliferative activity, particularly against HCT116 colon cancer cells. CDK1-IN-9 induces G2/M phase arrest and downregulates CDK1, cyclin B1, and the replication initiation factor CDC45. CDK1-IN-9 induces severe DNA replication stress, subsequently activating the p53 signaling pathway to trigger apoptosis. CDK1-IN-9 can be used for research on colon cancer, liver cancer and gastric cancer.