CDK2 Inhibitor

Multi-kinase-IN-4 (compound 5d) is multi-targeted kinase inhibitor, including VEGFR2, EGFR, HER2, and CDK2, with IC₅₀ values of 0.33, 0.22, 0.18 and 2.09 μM, respectively. Multi-kinase-IN-4 shows broad-spectrum anti-cancer activities against HepG2, MCF-7, MDA-231, and HeLa cell lines (IC₅₀ = 1.94–7.1 µM), but exhibits lower toxicity in the WI-38 cells (IC₅₀ = 40.85 µM). Multi-kinase-IN-4 induces apoptosis and arrests cell cycle at S phase in HepG2 cells. Multi-kinase-IN-4 has the potential for the research of cancer.

CDKI-83 is a potent CDK9 and CDK1 inhibitor with K_i values of 21 nM and 72 nM for CDK9/T1 and CDK1/B, respectively. CDKI-83 demonstrates effective anti-proliferative activity in human tumour cell lines with a GI₅₀<1 μM. CDKI-83 effectively induces apoptosis in A2780 human ovarian cancer cells. CDKI-83 reduces phosphorylation at Ser-2 of RNA polymerase II (RNAPII) by inhibiting cellular CDK9 activity, and down-regulates Mcl-1 and Bcl-2. CDKI-83 has the potential for anti-cancer research.

CDK2-IN-53 (compound 9) is a CDK2 inhibitor with anticancer activity. CDK2-IN-53 selectively inhibits the proliferation of HCT-116 and MCF-7cells with IC₅₀ values of 13.89 and 7.65 μM, respectively, while showing lower cytotoxicity toward normal lung fibroblast (WI-38) cells (IC₅₀ = 71.24 μM). CDK2-IN-53 can be used for cancer research, such as colon and breast cancer.

Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC₅₀s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC₅₀=0.5 μM) and GSK-3β (IC₅₀=1.5 μM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research.

CDK2-IN-54 (Formula I) is a CDK2 inhibitor. CDK2-IN-54 can be used in cancer research such as triple-negative breast cancer, ovarian cancer, bladder cancer, and uterine cancer.

Carbonic anhydrase inhibitor 14 (Compound 8b) is a carbonic anhydrase (CA) inhibitor with K_i values of 1203, 99.7, 9.4 and 27.7 nM against hCA I, hCA II, hCA IX and hCA XII, respectively. Carbonic anhydrase inhibitor 14 can also inhibit CDK2 with an IC₅₀ of 20.3 μM. Carbonic anhydrase inhibitor 14 shows antitumor activity.

PI3Kα-IN-26 (Compound 11e) is a PI3Kα inhibitor with an IC₅₀ of 75.31 nM. PI3Kα-IN-26 has a broad-spectrum anticancer activity, such as leukemia, colon and breast cancer, without significant cytotoxic effect on the normal Vero cells (mean IC₅₀s of 2.74, 3.50, 3.34 and 85.29 μM, respectively).

ALK-IN-29 (compound 4c) has a certain inhibitory effect on tyrosine protein kinases ALK, CDK2/CyclinE1 and FAK, among which the strongest inhibitory effect on ALK kinase is 40.63% at a concentration of 10 μM. ALK-IN-29 can be used for anti-cancer research.

Multi-target kinase-IN-7 (Compound 1e) is an orally active multi-target kinase inhibitor (IC₅₀ values: CDK2=0.314 μM, EGFR=0.183 μM, HER-2=0.197 μM, VEGFR-2=0.235 μM). Multi-target kinase-IN-7 is promising for research of solid tumors (e.g., lung, breast, prostate cancer).

CDK2/4/6-IN-1(example 29) is a CDK2/4/6 inhibitor with IC₅₀ values of 2.5, 23.7 and 44.3 nM for CDK2, CDK4 and CDK6, respectively. CDK2/4/6-IN-1 can be used in cancer research. CDK2/4/6-IN-1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

CDK5-IN-4 (compound 4) is a potent multikinase type-II inhibitor targeting CDK5, with an IC₅₀ of 9.8 μM. CDK5-IN-4 also inhibits GSK-3α, GSK-3β, CDK9, and CDK2, with IC₅₀ values of 0.98, 4.00, 1.76, and 6.24 μM, respectively. CDK5-IN-4 can be used for glioblastoma research.

CDK2/4/6-IN-3 (compound 32a) is a CDK2/4/6 inhibitor. CDK2/4/6-IN-3 can be used as a target protein ligand for the synthesis of PROTAC WWZ-11-098 (HY-181490).

Rohitukine is an orally active CDK9/T1 inhibitor with an IC₅₀ of 0.3 μM. Rohitukine blocks ATP binding sites of CDK2/A and CDK9/T1, suppresses PPARγ, AKT, mTOR, C/EBPα, SREBP-2, and NF-κB signaling, and increases hepatic LXRα expression. Rohitukine induces S-phase cell cycle arrest, ROS generation, apoptosis, and exhibits anti-inflammatory activity. Rohitukine can be used for the research of leukemia, pancreatic cancer, prostate cancer, breast cancer, CNS cancer, ovarian cancer, lung cancer, dyslipidemia, inflammatory diseases, inflammatory bowel disease, and arthritis.

CDK2-IN-8 is a potent CDK2 inhibitor with an IC₅₀ of 1.74 µM. CDK2-IN-8 shows antiproliferative activity. CDK2-IN-8 has the potential for the research of melanoma.

CDK9-IN-33 (compound C35) is a potent, selective and orally active CDK9 inhibitor with IC₅₀ values of 17.44, 160, 316.30, 1771.00, >10000 nM for CDK9, CDK7, CDK2, CDK4, CDK6 respectively. CDK9-IN-33 induces apoptosis. CDK9-IN-33 decreases the protein expression of RPB1 CTD Ser2, RPB1, MCL1. CDK9-IN-33 shows anti-tumor activity.

CDK5-IN-2 (compound 15) is a highly selective CDK5 inhibitor with IC₅₀s of 0.2 and 23 for CDK5/p25 and CDK2/CycA, respectively.

CDK2-IN-9 is a potent CDK2 inhibitor with an IC₅₀ of 0.63 µM. CDK2-IN-9 shows antiproliferative activity. CDK2-IN-9 induces apoptosis and cell cycle arrest at S and G2/M phase. CDK2-IN-9 has the potential for the research of melanoma.

CDK9-IN-50 is a selective and orally active CDK9 inhibitor with an IC₅₀ of 2.2 nM. CDK9-IN-50 targets a distinct CDK9-specific subpocket to disrupt RNA polymerase II Ser2 phosphorylation and downregulate short-lived oncoproteins, including AR-V7 and Myc. CDK9-IN-50 exhibits antiproliferative activity against cancer cells, induces apoptosis and induces tumor growth inhibition in CRPC orthotopic mice models. CDK9-IN-50 can be used for the research of cancer, such as prostate cancer.

TrkA Inhibitor (Compound 18) is a CDK2 inhibitor with an IC₅₀ of 0.69  μM over CDK1. TrkA Inhibitor can be used for chemotherapy-induced alopecia research.

CDK9-IN-22 is a potent CDK9 inhibitor with IC₅₀s of 10.4, 876.2 nM for CDK9, CDK, respectively. CDK9-IN-22 induces apoptosis and cell cycle arrests at G2/M phase. CDK9-IN-22 decreases the expression of p-RNAPII (S2) and CDK9 protein. CDK9-IN-22 shows antiproliferative and aiti-tumor activity.