CDK4 Inhibitor

Contragestazol (DL111-IT) is a non-hormonal antifertility agent. Contragestazol reduces the expression of Cyclin D1 and CDK4, increases the expression of total retinoblastoma protein (pRb), and decreases the level of hyperphosphorylated pRb. Contragestazol induces G₀/G₁ phase cell cycle arrest. Contragestazol inhibits embryonic development by inducing luteal cell apoptosis and reducing intrauterine polyamine levels. Contragestazol exhibits antitumor activity against prostate cancer, S180 tumor and H22 tumor. Contragestazol shows extremely potent activity in terminating early pregnancy in animals.

CDK2-IN-29 (Compound 13q) is an inhibitor for cyclin-dependent kinase (CDK), with IC₅₀ of 96 nM and 360 nM, for CDK 2 and CDK 4, respectively.

Autophagy agonist-1 (compound 22) is an Autophagy agonist. Autophagy agonist-1 exhibits significant anticancer activity against HepG2 cells and normal cells with IC₅₀s of 8.8 μM and > 50 μM. Autophagy agonist-1 induces G1/S phase cell cycle arrest and inhibits CDK4 and CyclinD1 expression while upregulating P21. Autophagy agonist-1 promotes the accumulation of autophagosomes and the proteins LC3 and PINK1, enhancing autophagy and mitophagy in HepG2 cells.

3-Methylthienyl-carbonyl-JNJ-7706621 is a potent and selective inhibitor of cyclin-dependent kinase (CDK), with IC₅₀s of 6.4 nM and 2 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. 3-Methylthienyl-carbonyl-JNJ-7706621 also shows potent inhibition of GSK-3 (IC₅₀=0.041 μM) and modest potency against CDK4, VEGF-R2, and FGF-R2 (IC₅₀=0.11, 0.13, 0.22 μM, respectively). 3-Methylthienyl-carbonyl-JNJ-7706621 can be used for the research of cancer.

CDK4-IN-6 is a CDK4 inhibitor with an IC₅₀ of 0.0011 μM. CDK4-IN-6 can be used for the research of breast cancer.

BMS-357075 is a pan-CDK inhibitor with CDK1 IC₅₀ 18 nM, CDK2 IC₅₀ 3 nM, CDK4 IC₅₀ 26 nM. BMS-357075 induces cytotoxicity in human ovarian cancer A2780 cells. BMS-357075 exhibits anticancer activity in mice against P388 murine leukemia. BMS-357075 can be used for the research of leukemia.

ZDLD13, a β-carboline, is an orally active and selective CDK4/CycD3 inhibitor with an IC₅₀ value of 0.38 μM. ZDLD13 exhibits potent anti-HCT116 activity including inhibition of colony formation, inhibition of invasion and migration, inducing of apoptosis, and arresting of G1 phase in cell cycle. ZDLD13 shows significant tumor growth inhibition in HCT116 tumor xenograft model.

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.

PRT3645 (Example 20) is a CDK Inhibitor. CDK-IN-12 Inhibits CDK4/6 with IC₅₀ values less than 20 nM.

SR-2890 is a highly selective, ATP-competitive inhibitor of casein kinase CK1δ and CK1ε, with IC₅₀ values ​​of 4 nM and 44 nM, respectively, and a K_i of 14 nM for CK1δ. SR-2890 exhibits antiproliferative effects. SR-2890 blocks the serine/threonine kinase activity of CK1δ and weakly inhibits a few off-target kinases such as FLT3, CDK4. SR-2890 has an oral bioavailability of 10% and a blood-brain barrier penetration rate of <1%. SR-2890 demonstrates stable in vitro metabolism and favorable in vivo pharmacokinetic properties, effectively inhibiting the growth of human A375 melanoma cells. SR-2890 can be used in melanoma research and is also a useful compound for studying CK1δ/ε-related diseases such as Alzheimer's disease.

JD128 (Compound 22) is a CDK4/6 inhibitor.

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.

Ulecaciclib is an orally activitive inhibitor of cyclin-dependent kinase (CDK), with K_i values of 0.62 μM (CDK2/Cyclin A), 0.2 nM (CDK4/Cyclin D1), 3 nM (CDK6/Cyclin D3), and 0.63 μM (CDK7/Cyclin H), respectively. Ulecaciclib can cross blood brain barrier and has good pharmacokinetic characteristics.

NUAK1-IN-2 (Compound 24) is a NUAK1 (IC₅₀ of 3.162 nM) and CDK2/4/6 inhibitor. NUAK1-IN-2 can be used in cancer, neurodevelopmental disorders and Alzheimer's disease research.

CDK4/6-IN-30 is a selective, orally active CDK4 and CDK6 inhibitor with IC₅₀ values of 10 nM and 16 nM, respectively. CDK4/6-IN-30 induces cell cycle arrest at G1 phase, inhibits RB phosphorylation, and decreases c-MYC and Cyclin D1 levels. CDK4/6-IN-30 exhibits anticancer activity against breast cancer. CDK4/6-IN-30 can be used for research on breast cancer.

CDK4/6-IN-26 is a carbamate derivative that targets CDK4/CDK6. CDK4/6-IN-26 reduces CDK4/CDK6 levels, resulting in cell cycle arrest in the G0/G1 phase and in the S phase. CDK4/6-IN-26 exhibits high potency against SW480 cells (IC₅₀ = 6.3 μM). CDK4/6-IN-26 affects ROS levels by increasing the expression of SOD2/MnSOD. CDK4/6-IN-26 establishes several interactions with the amino acids of the CDK6 active site. CDK4/6-IN-26 can be used for the research of colorectal 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.

CDK4/6-IN-8 (Compound 7p) is a selective CDK4 and CDK6 inhibitor with IC₅₀ values of 5.01 nM and 3.97 nM, respectively.

PROTAC CDK2/4/6 Degrader-1 is an orally active CDK2/CDK4/CDK6 PROTAC degrader. PROTAC CDK2/4/6 Degrader-1 is a prodrug derived from PROTAC CDK2/4/6 Degrader-2 via one-step reaction with chloromethyl pivalate. PROTAC CDK2/4/6 Degrader-1 can be used for malignant melanoma research.

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.