CDK4 Inhibitor

CGP60474, a highly potent anti-endotoxemic agent, is a potent cyclin-dependent kinase (CDK) inhibitor (IC₅₀ values are 26, 3, 4, 216, 10, 200 and 13 nM for CDK1/B, CDK2/E, CDK2/A, CDK4/D, CDK5/p25, CDK7/H and CDK9/T, respectively). CGP60474 is a selective and ATP-competitive PKC inhibitor.

Asnuciclib (CDKI-73; LS-007) is an orally active and highly efficacious CDK9 inhibitor, with K_i values of 4 nM, 4 nM and 3 nM for CDK9, CDK1 and CDK2, respectively. Asnuciclib down-regulates the RNAPII phosphorylation. Asnuciclib is also a novel pharmacological inhibitor of Rab11 cargo delivery and innate immune secretion.

Narazaciclib (ON123300), a strong and brain-penetrant multi-kinase inhibitor, inhibits CDK4 (IC₅₀=3.9 nM), Ark5 (IC₅₀=5 nM), PDGFRβ (IC₅₀=26 nM), FGFR1 (IC₅₀=26 nM), RET (IC₅₀=9.2 nM), and FYN (IC₅₀=11 nM). Single agent Narazaciclib causes a dose-dependent suppression of phosphorylation of Akt as well as activation of Erk in brain tumors. Narazaciclib inhibits CDK6 with an IC₅₀ of 9.82 nM.

Alisol B 23-acetate is an orally active prototerpane-type triterpenoid. Alisol B 23-acetate can be isolated from Alisma orientalis. Alisol B 23-acetate induces Apoptosis, promotes ROS generation, downregulates CDK4/6, MMP-2/9, upregulates cleaved PARP, activates FXR and inhibits Syk. Alisol B 23-acetate has anti-inflammatory and hepatoprotective activities. Alisol B 23-acetate protects the kidney from ischemia-reperfusion injury. Alisol B 23-acetate has anticancer activity against ovarian cancer, colon cancer, lung cancer, and gastric cancer. Alisol B 23-acetate can be used in the study of atherosclerosis and allergic asthma.

NU6102 is a potent CDK1 and CDK2 inhibitor with IC₅₀s of 9.5 nM and 5.4 nM for CDK1/cyclinB and CDK2/cyclinA3, respectively. NU6102 shows selectivity for CDK1/CDK2 over CDK4 (IC₅₀ of 1.6 μM), DYRK1A (IC₅₀ of 0.9 μM), PDK1 (IC₅₀ of 0.8 μM) and ROCKII (IC₅₀ of 0.6 μM).

Voruciclib is an orally active and selective CDK inhibitor with K_i values of 0.626 nM-9.1 nM. Voruciclib potently blocks CDK9, the transcriptional regulator of MCL-1. Voruciclib represses expression of MCL-1 in multiple models of diffuse large B-cell lymphoma (DLBCL).

Abemaciclib metabolite M2 (LSN2839567) is a metabolite of Abemaciclib, acts as a potent CDK4 and CDK6 inhibitor, with IC₅₀s of 1.2 and 1.3 nM, respectively. Anti-cancer activity.

Samuraciclib (CT7001) is a potent, selective, ATP-competitive and orally active CDK7 inhibitor, with an IC₅₀ of 41 nM. Samuraciclib displays 45-, 15-, 230- and 30-fold selectivity over CDK1, CDK2 (IC₅₀ of 578 nM), CDK5 and CDK9, respectively. Samuraciclib inhibits the growth of breast cancer cell lines with GI₅₀ values between 0.2-0.3 μM. Samuraciclib has anti-tumor effects.

Abemaciclib metabolite M18 (LSN3106729) hydrochloride, the metabolite of Abemaciclib (HY-16297A), is a CDK inhibitor with antitumor activity. Abemaciclib metabolite M18 hydrochloride and a CRBN ligand have been used to design PROTAC CDK4/6 degrader.

FN-1501 is a potent inhibitor of FLT3 and CDK, with IC₅₀s of 2.47, 0.85, 1.96, and 0.28 nM for CDK2/cyclin A, CDK4/cyclin D1, CDK6/cyclin D1 and FLT3, respectively. FN-1501 has anticancer activity.

Lerociclib dihydrochloride (G1T38 dihydrochloride) is a potent and selective inhibitor of CDK4/CDK6, with IC₅₀s of 1 nM and 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.

BS-181 hydrochloride is a highly selective CDK7 inhibitor with IC₅₀ of 21 nM, and > 40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.

MC180295 ((rel)-MC180295) is a potent and selective CDK9-Cyclin T1 inhibitor, with an IC₅₀ of 5 nM, at least 22-fold more selective for CDK9 over other CDKs. MC180295 also inhibits GSK-3α and GSK-3β. MC180295 ((rel)-MC180295) has potent anti-tumor effect.

Lerociclib (G1T38) is a potent and selective inhibitor of CDK4/6, with IC₅₀s of 1 nM, 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.

Tabersonine is a selective, orally active NLRP3 inhibitor. Tabersonine directly binds to the NACHT domain of NLRP3, inhibiting its ATPase activity and oligomerization, thereby blocking ASC spot formation and caspase-1 activation, and reducing the release of pro-inflammatory cytokines such as IL-1β. Tabersonine also inhibits K63-linked ubiquitination of TRAF6, blocking NF-κB, PI3K/Akt, and p38 MAPK signaling pathways. Tabersonine can inhibit inflammatory responses, induce apoptosis of liver cancer cells through mitochondrial pathways and death receptor pathways, reduce mitochondrial membrane potential, promote cytochrome c release, and activate caspase proteins. Tabersonine is mainly used in the study of NLRP3-driven inflammatory diseases (such as acute lung injury, sepsis, peritonitis) and tumors such as liver cancer.

Abemaciclib metabolite M20 (LSN3106726), the active metabolite of Abemaciclib, is a selective CDK4/6 inhibitor for the treatment of cancer.

β-catenin-IN-3 (Compound C2) is a selective β-catenin inhibitor. β-catenin-IN-3 binds to allosteric site on the surface of β-catenin with K _D calculated at 54.96 nM. β-catenin-IN-3 selectively inhibits β-catenin via targeting a cryptic allosteric modulation site, lowers its cellular load. β-catenin-IN-3 significantly reduces viability of β-catenin driven cancer cells, and triggers β-catenin degradation via proteasome system in β-catenin-overexpressing cancer cells.

Samuraciclib (CT7001) hydrochloride hydrate is a potent, selective, ATP-competitive and orally active CDK7 inhibitor, with an IC₅₀ of 41 nM. Samuraciclib hydrochloride hydrate displays 45-, 15-, 230- and 30-fold selectivity over CDK1, CDK2 (IC₅₀ of 578 nM), CDK5 and CDK9, respectively. Samuraciclib hydrochloride hydrate inhibits the growth of breast cancer cell lines with GI₅₀ values between 0.2-0.3 μM. Samuraciclib hydrochloride hydrate has anti-tumor effects.

BSJ-03-204 triTFA is a PROTAC-based CDK degrader derived from Palbociclib (HY-50767). BSJ-03-204 triTFA targets bovine CDK4/CCND1 and CDK6/CCND1 complexes with IC₅₀ values of 26.9 nM and 10.4 nM, respectively. BSJ-03-204 triTFA also triggers ubiquitination and degradation of RB1, reduces pRb levels, thereby inducing G1 cell cycle arrest and exerting antiproliferative effects, as well as inducing time-dependent KLHL8 accumulation. BSJ-03-204 triTFA can be used in research related to pancreatic ductal adenocarcinoma, breast cancer, lung cancer, mantle cell lymphoma, and cloned bovine placental hyperplasia.

TMX-3013 is a CDK inhibitor capable of inhibiting the activity of CDK1, CDK2, CDK4, CDK5, and CDK6, with IC₅₀ values of 0.9 nM, <0.5 nM, 24.5 nM, 0.5 nM, and 15.6 nM, respectively. TMX-3013 can be used as a target protein ligand, conjugated with the PROTAC linker and the CRBN ligand Thalidomide (HY-14658) for the synthesis of PROTAC TMX-2138 (HY-164906). TMX-3013 can also act as an effector ligand, binding to target proteins HaloTag or FKBP, and can be used in the synthesis of regulated induced proximity targeting chimeras (RIPTACs).