cdks

Toyocamycin (Vengicide) is an adenosine analog produced by Actinomycetes, functioning as an XBP1 inhibitor and inhibiting IRE1α-induced ATP-dependent XBP1 mRNA cleavage (IC50: 80 nM), and induces apoptosis.

SB1317 (TG02) is a potent inhibitor of cyclin dependant kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3).

BS194 is as a potent cyclin-dependent protein kinases (CDKs) inhibitor.

SNX7 (WAY-323879) is an inhibitor of the cell cycle protein-dependent kinase inhibitor (CDKI) pathway. SNX7 can be utilized as a tool for investigating the aging process and other diseases associated with CDKI.

FLT3 CDKs ligand-1 (Compound 14) functions as a ligand for target proteins, promoting the degradation of Cyclin-Dependent Kinases (CDK) and FMS-like tyrosine kinase 3 (FLT3), thereby inhibiting the proliferation and survival of leukemia cells associated with FLT3 CDK. This compound is also used in the synthesis of PROTAC FLT3 CDKs Degrader-1.

Flavopiridol (Alvocidib) (Alvocidib) competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM. It is 7.5-fold more selective for CDK1, 2, 4, 6 versus CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Phase 1 2.

CDK9-IN-7 is a highly selective and orally active CDK9 cyclin T inhibitor (IC50: 11 nM), which exhibits more potent over other CDKs (CDK4 cyclinD: 148 nM; CDK6 cyclinD: 145 nM).

9-Isopropylolomoucine (N9-Isopropylolomoucine), a cell cycle protein-dependent kinase inhibitor, is a thiopurine.

Ailanthone (AIL) is a natural compound derived from the tree Ailanthus altissima and has anti-hepatocellular carcinoma (HCC) properties. It can induce G0 G1 phase cell cycle arrest by downregulating the expression of cyclins and CDKs, while upregulating the expression of p21 and p27. Additionally, Ailanthone is a potent androgen receptor (AR) inhibitor, capable of inhibiting both the full-length androgen receptor (IC50: 69 nM) and constitutively active splice variants (IC50: 309 nM).

NU6140 is a selective inhibitor of CDK2-cyclin A (IC50, 0.41 μM). It shows 10- to 36-fold selectivity over other CDKs. NU6140 also effectively inhibits Aurora A and Aurora B (IC50s: 67 and 35 nM, respectively). It also enhances the apoptotic effect and has anti-cancer activity.

Roniciclib (BAY 1000394) is a potent pan-CDK inhibitor and a novel oral cytotoxic agent. Roniciclib inhibits the activity of cell-cycle CDKs CDK1, CDK2, CDK3, CDK4, and of transcriptional CDKs CDK7 and CDK9 with IC(50) values in the range between 5 and 25 nmol L.

TMX-3013 is a CDK inhibitor that targets multiple cyclin-dependent kinases, specifically suppressing 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. Additionally, TMX-3013 is utilized in the synthesis of PROTACs, which use polyethylene glycol (PEG) as a linker and Thalidomide as the CRBN-recruiting arm.

TMX-2172 is a heterobifunctional CDK2 degrader, selectively degrading CDK2 and CDK5, with minimal effects on CDK1, transcriptional CDKs (CDK7 and CDK9), and cell cycle CDKs (CDK4 and CDK6). In ovarian cancer cells (OVCAR8), its anti-proliferative activity is dependent on CDK2 degradation and is linked to high expression of cyclin E1 (CCNE1), which acts as a regulatory subunit of CDK2. As a lead compound for further development, TMX-2172 demonstrates that CDK2 degradation could be a potentially effective strategy for treating ovarian and other cancers with elevated CCNE1 expression.

TMX-2138 is a CDKs PROTAC degrader, with IC50 values of 8.7 nM for CDK1 cyclinB, 10.9 nM for CDK2 cyclinA, 7.0 nM for CDK5 p25, and 25.7 nM for CDK9 cyclinT1. It enhances the ubiquitination and degradation of CDKs and is utilized for ovarian cancer research.

TMX-2039 is a pan-CDK inhibitor that targets cell cycle CDKs (CDK1, CDK2, CDK4, CDK5, and CDK6) and transcription CDKs (CDK7 and CDK9), with IC50 values of 2.6, 1.0, 52.1, 0.5, 35.0, 32.5, and 25 nM, respectively. It serves as a ligand for the target protein in PROTAC applications.

Zeltociclib is an inhibitor of cyclin-dependent kinases (CDKs) with anti-tumor properties.

PF-562271 hydrochloride (PF-562271 HCl) is a potent, ATP-competitive, reversible inhibitor of FAK with IC50 of 1.5 nM in cell-free assays, ~10-fold less potent for Pyk2 than FAK and >100-fold selectivity against other protein kinases, except for some CDKs.

CDKs and GSK-3 inhibitor

Flavopiridol hydrochloride (MDL 107826A) is a synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis. This agent is also a competitive inhibitor of adenosine triphosphate activity.

RGB-286147 is a potent, selective, ATP-competitive Cdks inhibitor.

Olomoucine II is an inhibitor of cyclin-dependent kinases (CDKs; IC50s = 7.6, 0.1, 19.8, 0.45, and 0.06 μM for Cdk1, -2, -4, -7, and -9, respectively).1It is selective for CDKs over 10 additional kinases (IC50s = >100 μM for all) but does inhibit ERK2 (IC50= 32 μM) and the ATP-binding cassette transporter B1 (ABCB1; IC50= 6.4 μM).1,2Olomoucine II inhibits proliferation of a variety of cancer cells, including those expressing wild-type p53 or mutant p53 (mean IC50s = 7.4 and 10.1 μM, respectively), and it acts synergistically with daunorubicin to inhibit proliferation of HCT-8 cells that endogenously express ABCB1. Olomoucine also inhibits replication of herpes simplex virus 1 (HSV-1), HSV-2, vaccinia virus, human adenovirus type 4 (Ad4), and human CMV (IC50s = 5, 4.7, 3.8, 2.4, and 3.2 μM, respectively) but not measles virus or influenza virus (IC50s = >20 μM for both).3

6-Chloro-2-fluoropurine is a heterocyclic building block.1,2It has been used in the synthesis of purine nucleosides that inhibit cyclin-dependent kinases (CDKs)in vitro.16-Chloro-2-fluoropurine has also been used in the synthesis of purine nucleosides that are active against HIV-1 and hepatitis B virus (HBV)in vitro.2 1.Wilson, S.C., Atrash, B., Barlow, C., et al.Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitorsBioorg. Med. Chem.19(22)6949-6965(2011) 2.Lee, K., Choi, Y., Gullen, E., et al.Synthesis and anti-HIV and anti-HBV activities of 2'-fluoro-2',3'-unsaturated L-nucleosidesJ. Med. Chem.42(7)1320-1328(1999)

Tanuxiciclib is a cyclin dependent kinase (CDK) inhibitor, specifically designed to interfere with cell cycle progression by inhibiting the activity of CDKs, which are crucial regulators of cell division.

Histone H1-derived peptide is a phosphopeptide with peptide substrates that consist of a sequence aligned with the optimal recognition motif for cyclin-dependent kinases (CDKs).