CDK Inhibitor

CCT-251921 is a potent, selective, and orally bioavailable CDK8 inhibitor with an IC₅₀ of 2.3 nM.

BSJ-04-132 is a PROTAC connected by ligands for Cereblon and CDK. BSJ-04-132 is a potent and selective Ribociclib-based CDK4 degrader (PROTAC), with IC₅₀s of 50.6 nM and 30 nM for CDK4/D1 and CDK6/D1, respectively. BSJ-04-132 does not induce CDK6 and IKZF1/3 degradation. BSJ-04-132 has anti-cancer activity.

PHA-793887 is a CDK inhibitor (with IC₅₀ values of 8 nM for Cdk2, 60 nM for Cdk1, 62 nM for Cdk4, 138 nM for Cdk9). PHA-793887 inhibits purified GSK3β (IC₅₀ 79 nM). PHA-793887 reduces the phosphorylation level of nucleophosmin/cdc6, induces G1/G2/M phase arrest, and triggers Apoptosis by activating Caspase-3. PHA-793887 exhibits anticancer activity against leukemia. PHA-793887 can be used in research related to acute leukemia, chronic myeloid leukemia, and advanced/metastatic solid tumors.

Atuveciclib (BAY-1143572) is a potent and highly selective, oral PTEFb/CDK9 inhibitor. Atuveciclib (BAY-1143572) inhibits CDK9/CycT1 with an IC₅₀ of 13 nM.

LDC000067 is a highly specific CDK9 inhibitor with an IC₅₀ value of 44±10 nM in vitro.

Milciclib (PHA-848125) is a potent, ATP-competitive and dual inhibitor of CDK and Tropomyosin receptor kinase (TRK), with IC₅₀s of 45, 150, 160, 363, 398 nM and 53 nM for cyclin A/CDK2, cyclin H/CDK7, cyclin D1/CDK4, cyclin E/CDK2, cyclin B/CDK1 and TRKA, respectively.

AZ5576 is a potent and highly selective CDK9 inhibitor (IC₅₀: <5 nM). AZ5576 inhibits the phosphorylation of RNA polymerase II at Ser2, thereby inhibiting transcriptional elongation. AZ5576 can be used for hematological Malignancy research.

SU9516 is a potent CDK2 inhibitor, with an IC₅₀ of 22 nM, and also shows inhibitory effects on CDK1 and CDK4, with IC₅₀s of 40, 200 nM, respectively.

GFB-12811 is a high selective CDK5 inhibitor with an IC₅₀ of 2.3 nM.

RGB-286638 is a potent inhibitor of CDK and MAPK9. RGB-286638 inhibits the activities of cyclin T1-CDK9, cyclin B1-CDK1, cyclin E-CDK2, cyclin D1-CDK4, cyclin E-CDK3 and p35-CDK5, with IC₅₀ values of 1, 2, 3, 4, 5 and 5 nM, respectively. RGB-286638 inhibits GSK-3β and TAK1, with IC₅₀ values of 3 nM and 5 nM, respectively. RGB-286638 induces caspase-dependent Apoptosis in cells. RGB-286638 delays tumor growth in an orthotopic glioblastoma mouse model. RGB-286638 extends survival in multiple myeloma models. RGB-286638 can be used in research related to glioblastoma and multiple myeloma.

Cucurbitacin E is a CDK1 inhibitor that significantly inhibits the activity of the cyclin B1/CDC2 complex. Cucurbitacin E also induces PANoptosis in adrenocortical carcinoma cells in a ZBP1-dependent manner. Cucurbitacin E exhibits synergistic effects with Mitotane (HY-13690); when used in combination, they effectively eliminate tumors.

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.

PHA-767491 hydrochloride is a dual Cdc7/Cdk9 inhibitor, with IC₅₀s of 10 nM and 34 nM, respectively.

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.

β,β-Dimethylacrylalkannin (Arnebin 1) is an orally active FGFR1 inhibitor (IC₅₀=2.5 μM) and the main active component of Lithospermum erythrorhizon. β,β-Dimethylacrylalkannin blocks downstream signaling by binding to the ATP pocket of FGFR1, and regulates the CDK1/Cdc25C pathway and ROS-JNK axis, thereby inducing G2/M phase arrest, necrosis and apoptosis in cancer cells, and inhibiting tumor proliferation. β,β-Dimethylacrylalkannin also acts as a colistin adjuvant to disrupt the cell membrane of Gram-negative bacteria. β,β-Dimethylacrylalkannin exhibits significant tumor-inhibitory effects with no obvious toxicity in PDX models, but chronic exposure to high doses may alter the relative lung/liver weights of rats, while acute exposure to high doses causes responses such as reduced motor activity. β,β-Dimethylacrylalkannin finds wide application in studies related to hepatocellular carcinoma, colorectal cancer, colistin-resistant bacterial infections, hepatitis and psoriasis.

CDK2-IN-4 (compound 73) is a potent and selective CDK2 inhibitor with an IC₅₀ of 44 nM for CDK2/cyclin A, shows 2,000-fold selectivity over CDK1/cyclin B (IC₅₀=86 uM).

XL413 monohydrochloride (BMS-863233 monohydrochloride) is an orally active, ATP-competitive, selective CDC7 kinase inhibitor. XL413 monohydrochloride reduces MCM2 phosphorylation levels, decreases DNA replication origin activation, and inhibits CD69 upregulation in stimulated lymphocytes. XL-413 possesses cell-dependent antiproliferative and pro-apoptotic activities. XL413 monohydrochloride attenuates ATR inhibitor-induced excessive origin activation, altered replication fork speed, and antiproliferative effects in sensitive cancer cells. XL413 monohydrochloride inhibits SARS-CoV-2 infection. XL413 monohydrochloride can be used for research related to cancer and SARS-CoV-2 infection.

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.

SB-218078 is a potent, selective, ATP-competitive and cell-permeable checkpoint kinase 1 (Chk1) inhibitor that inhibits Chk1 phosphorylation of cdc25C with an IC₅₀ of 15 nM. SB-218078 is less potently inhibits Cdc2 (IC₅₀ of 250 nM) and PKC (IC₅₀ of 1000 nM). SB-218078 causes apoptosis by DNA damage and cell cycle arrest.