NSC 625987 is a specific and high-affinity CDK4 inhibitor with an IC50 of 0.2 μM for CDK4:cyclin D1. NSC 625987 shows >500-fold selectivity for CDK4 over CDK2[1].
Aloisine RP106 (compound 38) is a potent inhibitor of Cdk1/cyclin B, Cdk5/p25, and GSK3 with IC50s of 0.70µM, 1.5µM, 0.92 µM, respectively[1].
Flavopiridol is a broad spectrum and competitive inhibitor of CDKs, inhibiting CDK1, CDK2, CDK4 with IC50s of 30, 170, 100 nM, respectively.
CDK12-IN-4, a pyrazolotriazine, is a potent CDK12 inhibitor with an IC50 of 0.641 μM at high ATP (2 mM). CDK12-IN-4 has no effect on CDK2/Cyclin E (IC50>20 μM) and CDK9/Cyclin T1 (IC50>20 μM) at high ATP (2 mM) (WO2021116178A1)[1].
SRX3177 is a potent, triple BRD4/PI3K/CDK4/6 inhibitor with nanomolar potency against PI3Kα (IC50=79 nM), BRD4 bromodomains (BD1 and BD2) (IC50=33 nM and 89 nM, respectively), and CDK4/6 (IC50=2.5/3.3 nM).SRX3177 is capable of targeting BRD4, PI3K and CDK4/6 simultaneously, induces apoptosis and cell cycle arrest and has in vitro efficacy in mantle cell lymphoma, hepatocellular carcinoma and neuroblastoma models.SRX3177 has antitumor efficacy in in vivo xenograft models and is less toxic than the combination of agents that inhibit individual targets.
Cdc7-IN-10 is a highly potent Cdc7 inhibitor with IC50≤1 nM. Cdc7-IN-10 can be used for researching proliferative diseases[1].
Cdc7-IN-1 (Compound 13) is a highly potent, selective and ATP competitive inhibitor of Cdc7 kinase, with an IC50 value of 0.6 nM at 1 mM ATP and with slow off-rate characteristics. Cdc7-IN-1 potently inhibits Cdc7 activity in cancer cells, and effectively induces cell death[1].
RSS0680 (Example 22) is a bifunctional compound targeted protein degradation of kinases. RSS0680 degrades AAK1, CDK1, CDK16, CDK2, CDK4, CDK6, EIF2AK4, GAK, LATSl, LIMK2, MAPK6, MAPKAPK5, MARK2, MARK4, MKNK2, NEK9, RPS6KB1, SIK2, SNRK, STK17A, STK17B, STK35, and WEEl. RSS0680 can be used for research of disease or disorder mediated by aberrant kinase activity[1].
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[1][2].
CDK7-IN-7 is a potent and selective CDK7 kinase inhibitor with an IC50 of <50 nM (Patent CN112661745A, compound T-01)[1].
DB0614 (Example 21) is a bifunctional compound targeted protein degradation of kinases. DB0614 degrades AAK1, AURKA, BMP2K, CAMKK1, CDK16, CML, CDK6, EIF2AK2, FER, GAK, LCK, LIMK2, MAP3KH, MAPK8, MAPK9, NEK9, PLK4, PTK2B, SIK2, STK17A, STK17B, ULK1, ULK3, and WEE1. DB0614 can be used for research of disease or disorder mediated by aberrant kinase activity[1].
CDK7-IN-13 is a potent inhibitor of CDK7. CDK7-IN-13 is a pyrimidinyl derivative compound. CDK7-IN-13 has the potential for the research of various cancers, especially the cancer with transcriptional dysregulation (extracted from patent CN114249712A, compound 1)[1].
NSC 107512 is a potent inhibitor of cyclin-dependent kinase 9 (CDK9). NSC 107512 is a class of sangivamycin-like molecules (SLM). NSC 107512 inhibits growth and induces apoptosis of multiple myeloma tumors[1].
Casein Kinase inhibitor A86 (CKIα inhibitor A86) is a novel pan-specific CKI (CSNK1) inhibitor (Kd=1-10 nM, CKIα Kd=9.8 nM) that co-targets the transcriptional kinases CDK7 and CDK9, with hardly inhibition of CDK8, CDK13, CDK11a, CDK11b, and CDK19; target both CDK7 and CDK9 with low nM Kd values; induces leukemia cell apoptosis at <160 nM, in correlation to the capacity to stabilize p53; shows high and selective sensitivity against leukemic CFUs in colony-forming unit (CFU) assay, without effect on normal hematopoietic CFUs; blocking CKIα together with CDK7 and/or CDK9 synergistically stabilize p53, deprive leukemia cells of survival and proliferation-maintaining SE-driven oncogenes, induce apoptosis, abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1; demonstrates therapeutic efficacy with preserved hematopoiesis and leukemia cure potential in AML mouse models.
AG-494 (Tyrphostin AG 494) is a potent and selective EGFR tyrosine kinase inhibitor (IC50=0.7 μM). AG-494 inhibits the autophosphorylation of EGFR, ErbB2, HER1-2 and PDGF-R with IC50s 1.1, 39, 45 and 6 μM, respectively. AG-494 blocks Cdk2 activation and inhibits EGF-dependent DNA synthesis[1][2][3].
Avotaciclib (BEY1107) trihydrochloride is a potent and orally active inhibitor of cyclin dependent kinase 1 (CDK1). Avotaciclib trihydrochloride can be used for the research of locally advanced or metastatic pancreatic cancer[1].
Senexin C is a novel potent, selective and orally bioavailable CDK8/19 inhibitor with Kd of 1.4 and 2.9 nM for CDK8/CycC and CDK19/CycC, respectively.Senexin C inhibits CDK8/CycC with IC50 of 3.6 nM, shows high selectivity against other HDAC isoforms.Senexin C is more metabolically stable and provides a more sustained inhibition of CDK8/19-dependent cellular gene expression when compared with the prototype inhibitor Senexin B.Senexin C inhibits MV4-11 leukemia growth in a systemic in vivo model with good tolerability.
A novel potent, selective CDK8 inhibitor with IC50 of 0.5 uM against recombinant Cyclin C/CDK8 complex; displays no activity against several CDKs involved in cell cycle including CDK19 (IC50>30 uM); inhibits IFNγ-induced phosphorylation of STAT1 at Ser 727 site in BMDCs, selectively upregulates IL-10 with EC50 of 1 uM.
MeBIO is a potent AhR (aryl hydrocarbon receptor) agonist, with IC50 of 44 μM (GSK-3) and 55 μM (CDK1/cyclin B), respectively. MeBIO is inactive on GSK-3β[1].
Borrelidin (Treponemycin) is a nitrile-containing macrolide antibiotic isolated from Streptomyces rochei, which acts as an inhibitor of bacterial and eukaryal threonyl-tRNA synthetase, can target ALL cell lines by inducing apoptosis and mediating G(1) arrest. Borrelidin (Treponemycin) is an inhibitor of a cyclin-dependent kinase (CDK) of the budding yeast, Cdc28/Cln2 with an IC50 of 24 μM. Borrelidin (Treponemycin) is a potent angiogenesis inhibitor with an IC50 of 0.8 nM for capillary tube formation, and induces apoptosis of the tube-forming cells. Borrelidin (Treponemycin) has strong antimalarial activities, with IC50s of 1.9 nM and 1.8 nM against K1 and FCR3 strains of Plasmodium falciparum[1][2][3].
CDK9-IN-30 is a CDK9 inhibitor that inhibits HIV-1 viral replication[1].
Leucettinib-92 (compound 92) is an inhibitor of DYRK/CLK kinase, The IC50s are 147 nM (CLK1), 39 nM (CLK2), 5.2 nM (CLK4), 0.8 μM (CLK3), 124 nM (DYRK1A), 204 nM (DYRK1B), 0.16 μM (DYRK2), respectively. 1.0 μM (DYRK3), 0.52 μM (DYRK4), 2.78 μM (GSK3)[1].
BSJ-01-175 is a potent and selective CDK12/13 covalent inhibitor. BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells[1].
ABC1183 is a potent, selective, orally active GSK3α/β and CDK9 inhibitor with IC50 of 327/657 nM and 321 nM (CDK9/cyclin T1), shows growth inhibitory activity against a broad panel of cancer cell lines; decreases cell survival through G2/M arrest and modulates oncogenic signaling through changes in GSK3, GS and β-catenin phosphorylation and MCL1 expression; suppresses tumor growth and inflammation-driven gastrointestinal disease symptoms without organ or hematological toxicity in vivo.
CDK8-IN-10 (compound 2) is a potent, selective cyclin-dependent kinase (CDK8) inhibitor with an IC50 value of 8.25 nM. CDK8-IN-10 can be used for research of cancer[1].
GSK-3 inhibitor 3 is a selective, orally active and brain-penetrant inhibitor of GSK-3, with IC50s of 0.35 nM and 0.25 nM for GSK-3α and GSK-3β, respectively. GSK-3 inhibitor 3 lowers levels of tau protein phosphorylation at S396 in a triple-transgenic mouse Alzheimer’s disease model, with IC50 of 10 nM. GSK-3 inhibitor 3 can be used for neurological disease research[1].
Ipivivint, a first-in-class, orally active and potent CDC-like kinase (CLK) inhibitor, inhibits CLK1 (IC50=1.4 μM), CLK2 (IC50=0.002 μM) and CLK3 (IC50=0.022 μM). Ipivivint reduces Wnt pathway signaling gene expression through inhibiting CLK activity and serine and arginine rich splicing factor (SRSF) phosphorylation and disrupting spliceosome activity. Ipivivint can be used for the research of cancer[1].
Riviciclib (P276-00 free base) is a potent CDK9-cyclinT1, CDK4-cyclin D1, CDK1-cyclinB, CDK2-cyclin A, CDK2-cyclin E, CDK6-cyclin D3, and CDK9-cyclin H inhibitor with IC50 values of 20 nM, 63 nM, 79 nM, 224 nM, 2500 nM, 396 nM, 2900 nM, respectively[1].Riviciclib shows antitumor activity on cisplatin-resistant cells[3].
BI-1347 is a potent CDK8 inhibitor extracted from patent WO2017202719A1, product I-003, has an IC50 of 1.1 nM[1].
LK1/2-IN-3 (compound 3) is a potent and selective CLK1 and CLK2 inhibitor with IC50 values of 1.1, 2.1, 130, 260, 260 nM for CLK1, CLK2, SRPK1, SRPK2, SRPK3, respectively. CLK1/2-IN-3 shows anti-proliferative activity. CLK1/2-IN-3 reduces the levels of endogenous phosphorylated SR proteins and increases the expression of S6K mRNAs[1].