NEKs Inhibitor

Ofirnoflastum (Ofirnoflast) is an orally active first-in-class allosteric NEK7 inhibitor with an IC₅₀ of 46 nM. Ofirnoflastum binds an allosteric site adjacent to NEK7’s ATP-binding pocket, induces conformational shifts, disrupts NEK7-NLRP3 binding, blocks NLRP3 inflammasome assembly, spares NEK7’s physiological functions, and suppresses caspase-1, caspase-8, NF-κB, and TNF activity. Ofirnoflastum reduces pro-inflammatory cytokine production, suppresses ASC specks, IL-1β release, pyroptotic cell death, and leukemic burden, induces apoptosis and erythroid differentiation, restores hematopoiesis, and improves outcomes in colitis models. Ofirnoflastum can be used for the research of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

T-1101 tosylate (TAI-95 tosylate) is the tosylate salt form of T-1101 (HY-120356). T-1101 tosylate is an orally active inhibitor for mitose regulating highly expressed oncoprotein 1 (Hec1). T-1101 tosylate blocks the interaction between Hec1 and NEK2, exhibits cytotoxicity in human liver cancer cells with GI₅₀ of 15-70 nM. T-1101 tosylate induces apoptosis in Huh-7. T-1101 tosylate exhibits antitumor efficacy in mouse models.

AP4-43 is an orally active CLK1, CLK4, PI3K, DDR1, EGFR and NEK4 inhibitor. AP4-43 reduces growth of mammalian colorectal cancer organoids. AP4-43 improves survival in a transgenic Drosophila model of KRAS-mutant colorectal cancer. AP4-43 can be used for the research of KRAS-mutant colorectal cancer.

CG-1521 is a histone deacetylase (HDAC) inhibitor that stabilizes Ac-Lys373 P53, increases P21 levels and HDAC2 degradation. CG-1521 can inhibit proliferation, induce cell cycle arrest and apoptosis. CG-1521 promotes Bax translocation to the mitochondria and cleavage. CG-1521 downregulates KIF4, Aurora B and Nek2 protein expression and DNA synthesis. CG-1521 can be used for the research of prostate cancer and inflammatory breast cancer.

MBM-55 is a potent NIMA-related kinase 2 (Nek2) inhibitor with an IC₅₀ of 1 nM. MBM-55 shows a 20-fold or greater selectivity in most kinases with the exception of RSK1 (IC₅₀=5.4 nM) and DYRK1a (IC₅₀=6.5 nM). MBM-55 effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-55 shows antitumor activities, and no obvious toxicity to mice.

INH1 specifically disrupts the Hec1/Nek2 interaction via direct Hec1 binding. INH1 shows promising cancer inhibition activity both in vitro and in vivo.

NBI-961 is a NEK2 catalytic inhibitor with human NEK2 IC₅₀ ~12-fold lower than FLT3. NBI-961 induces proteasomal degradation of NEK2. NBI-961 induces G2/mitosis arrest, apoptosis, and compromises viability in DLBCL cells and patient-derived cells. NBI-961 sensitizes DLBCL cells to doxorubicin and vincristine, and suppresses DLBCL tumor growth in mice. NBI-961 can be used for the research of diffuse large b cell lymphoma.

SLC3037 is a NLRP3 inhibitor which blocks NLRP3 from binding to NEK7 or oligomerization, inhibiting inflammasome caused by MSU and other inflammasome activators. SLC3037 can be used for research of gout, cardiovascular diseases, metabolic syndrome or neurodegenerative diseases.

INH6 is a potent Nek2/Hec1 inhibitor; inhibits the growth of HeLa cells with an IC₅₀ of 2.4 μM.

TAI-1, an orally active anticancer agent, is a highly potent first-in-class Hec1 inhibitor, with a GI₅₀ of 13.48 nM in K562 cells.

CK7, a Cdk2/9 inhibitor, can be used for the synthesis of Nek1 inhibitor BSc5231 and BSc5367.

NLRP3-IN-79 is an orally active NLRP3 inhibitor. NLRP3-IN-79 inhibits NLRP3 inflammasome with an IC₅₀ of 10.69 nM. NLRP3-IN-79 blocks NLRP3 inflammasome assembly by directly binding to NLRP3 and disrupting the NEK7-NLRP3 interaction. NLRP3-IN-79 can be used for the study of NLRP3-driven diseases model, including systemic inflammation, peritonitis, and colitis.

Nek2/Hec1-IN-3 (Compound 11-28) is a Hec1/Nek2 interaction inhibitor. Nek2/Hec1-IN-3 disrupts Nek2/Hec1 binding and can be used for research of neoplastic diseases.

MBM-17S is a potent NIMA-related kinase 2 (Nek2) inhibitor, with an IC₅₀ of 3 nM. MBM-17S effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-17S shows antitumor activities, and no obvious toxicity to mice.

NEK7-IN-1 (Compound I-15) is the inhibitor for NIMA-related kinase 7 NEK7 with IC₅₀ <100 nM. NEK7-IN-1 inhibits the IL-1β release with IC₅₀ <50 nM.

MBM-55S is a potent NIMA-related kinase 2 (Nek2) inhibitor with an IC₅₀ of 1 nM. MBM-55S shows a 20-fold or greater selectivity in most kinases with the exception of RSK1 (IC₅₀=5.4 nM) and DYRK1a (IC₅₀=6.5 nM). MBM-55S effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-55S shows antitumor activities, and no obvious toxicity to mice.

MBM-17 is a potent NIMA-related kinase 2 (Nek2) inhibitor with an IC₅₀ of 3 nM. It effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-55 shows antitumor activities, and no obvious toxicity to mice.

NEK7-IN-2 is a NEK7 inhibitor. NEK7-IN-2 increases the thermal stability of NEK7, disrupts the NEK7-NLRP3 interaction, inhibits NLRP3 inflammasome assembly, and suppresses the release of IL-1β (with an IC₅₀ of 0.048 μM against IL-1β). NEK7-IN-2 can be used for the research of inflammatory diseases.

HCI-2184 is a Nek2 inhibitor with an IC₅₀ of 39.90 nM. HCI-2184 significantly increases the effectiveness of Bortezomib (HY-10227) in inhibiting proteasome activity.

T-1101 (TAI-95) is an orally active inhibitor for mitose regulating highly expressed oncoprotein 1 (Hec1). T-1101 blocks the interaction between Hec1 and NEK2, exhibits cytotoxicity in human liver cancer cells with GI₅₀ of 15-70 nM. T-1101 induces apoptosis in Huh-7. T-1101 exhibits antitumor efficacy in mouse models.