ULK

SBI-0206965 is a potent, selective and cell permeable autophagy kinase ULK1 inhibitor with IC50 of 108 nM for ULK1 kinase activity and 711 nM for the highly related kinase ULK2 .

MRT68921 is a potent and dual autophagy kinase ULK1/2 inhibitor with IC50 of 2.9 nM and 1.1 nM, respectively.

LYN-1604 is a potential ULK1 agonist with IC50 of 1.66 μM against MDA-MB-231 cells and it binds to wild-type ULK1 with a binding affinity in the nanomole range (Kd=291.4 nM). The ULK1 (Y89A) mutant protein caused a sharp decrease in binding affinity with lower response and Kd than wild-type ULK1, ULK1 (K50A) and ULK1 (L53A) mutants.

LYN-1604 hydrochloride is a potent ULK1 activator with an EC50 of 18.94 nM.

MRT68921 dihydrochloride is the most potent inhibitor of ULK1 and ULK2, with IC50 values of 2.9 nM and 1.1 nM, respectively.

SBP-7455 is a potent, high affinity and orally active dual ULK1/ULK2 autophagy inhibitor with IC50s of 13 nM and 476 nM in the ADP-Glo assays, respectively.

LYN-1604 dihydrochloride is a potent UNC-51-like kinase 1 (ULK1) activator (EC50=18.94 nM) for the research of triple negative breast cancer (TNBC).

BL-918 is an orally active UNC-51-like kinase 1 (ULK1) activator with an EC50 of 24.14 nM.

DCC-3116 is an orally active inhibitor of ULK1/2 that suppresses autophagy in lung cancer cells. By targeting ULK1/2, DCC-3116 inhibits KRAS^G12C-driven signaling pathways, leading to reduced cell proliferation and demonstrating anti-tumor activity in KRAS-mutant lung cancer models.

HS-276 is an orally bioavailable, potent, and highly selective inhibitor of transforming growth factor-β–activated kinase 1 (TAK1), with a Kᵢ of 2.5 nM. It exhibits strong inhibition of TAK1 and moderate activity against a panel of other kinases, including CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with respective IC₅₀ values ranging from 8.25 to 5585 nM. HS-276 is a valuable tool for investigating TAK1-mediated signaling pathways and holds therapeutic potential for inflammatory conditions such as rheumatoid arthritis (RA).

ULK1-IN-2 is a potent inhibitor of ULK1, a key regulator of autophagy. This compound exhibits significant cytotoxic effects against cancer cell lines, demonstrating an IC50 of 1.94 μM in A549 cells. ULK1-IN-2 not only induces apoptosis but also effectively inhibits autophagy, making it a valuable tool for research applications in non-small cell lung cancer (NSCLC) studies.

XST-14 is a potent and selective inhibitor of ULK1, demonstrating an IC50 of 26.6 nM. This compound effectively inhibits autophagy by decreasing the phosphorylation of ULK1 downstream substrates. XST-14 has been shown to induce apoptosis in hepatocellular carcinoma (HCC) cells, providing significant antitumor effects and contributing to ongoing cancer research and therapeutic studies.

MRT67307 hydrochloride is a selective inhibitor of IKKε and TBK-1, exhibiting IC50 values of 160 nM and 19 nM, respectively. Additionally, it inhibits ULK1 and ULK2 with IC50s of 45 nM and 38 nM, respectively. This compound is employed in research to study autophagy regulation and related cellular processes. It is particularly useful in investigations of inflammatory signaling pathways and cancer biology.

MR-2088 is a selective, ATP-competitive inhibitor of ULK1 and ULK2, exhibiting pEC50 values of 8.3 and 8.7, respectively. This compound effectively inhibits autophagic flux and demonstrates a synergistic antiproliferative effect with MEK inhibitors in vitro, making it a valuable tool for studying non-small cell lung cancer (NSCLC). Its ability to modulate autophagy-related pathways provides insights into cancer biology and potential therapeutic strategies.

(Z/E)-GW406108X serves as a selective inhibitor of Kif15, a member of the Kinesin-12 family, with an IC50 of 0.82 µM. This compound is instrumental in studying the dynamics of mitotic processes and cellular transport mechanisms. Additionally, it may have implications in cancer research, specifically in the investigation of tumor cell proliferation and migration.

MRT67307 dihydrochloride is a potent inhibitor of IKKε and TBK-1, demonstrating IC50 values of 160 nM and 19 nM, respectively. Additionally, this compound inhibits ULK1 and ULK2 with IC50s of 45 nM and 38 nM, respectively. MRT67307 dihydrochloride plays a significant role in blocking autophagy in cellular environments, making it a valuable tool for studies involving inflammation and autophagic processes.

SBP-5147 is a potent inhibitor of ULK1 and ULK2, exhibiting an IC50 of 2 nM for ULK1 and 53 nM for ULK2. This compound effectively inhibits the phosphorylation of Beclin-1 and Vps34, reduces autophagic flux, and downregulates the expression of key autophagy-related proteins ATG13 and ATG101. Additionally, SBP-5147 enhances MHC-I expression, induces caspase-dependent apoptosis, and decreases the viability of non-small cell lung cancer cells. Its mechanism of action makes SBP-5147 a valuable tool for research in non-small cell lung cancer and autophagy modulation.

GW406108X is a selective inhibitor of Kif15 (Kinesin-12) and exhibits a significant inhibition of ULK1 kinase activity with a pIC50 of 6.37 (427 nM). This compound demonstrates potent autophagy inhibition, effectively blocking autophagic flux without impacting upstream signaling pathways such as mTORC1 and AMPK. GW406108X serves as a valuable tool in research focusing on autophagy regulation and related cellular processes.

NZ-66 is a chimera that targets UNC-51-like kinase 1 (ULK1), facilitating proximity-induced degradation of mitochondria through ULK1 activation. This compound effectively induces mitophagy, making it a valuable tool for studying mitochondrial quality control processes. Additionally, NZ-66 holds potential in research related to neurodegenerative disorders, offering insights into therapeutic strategies for these conditions.

ULK-101 is a highly selective inhibitor of ULK1, demonstrating an IC50 of 1.6 nM for ULK1 and 30 nM for ULK2. This compound effectively suppresses autophagy processes, making it valuable for cancer research, particularly in studies focused on nutrient stress sensitivity in cancer cells. ULK-101 is suitable for applications requiring modulation of autophagy and exploration of related signaling pathways.

SBP-1750 is a potent ULK1/2 inhibitor and an effective degrader of ATG13. It demonstrates strong inhibition of ULK1 and ULK2 with IC50 values of 8 nM and 50 nM, respectively, while inducing ATG13 degradation with an EC50 of 114 nM. By inhibiting autophagy, SBP-1750 can promote cell death in cancer cells, making it a valuable tool for research in cancer biology, particularly in the study of pancreatic cancer.

ULK-100 is a potent and selective inhibitor of ULK1 kinase, exhibiting an IC50 value of 1.6 nM. This compound demonstrates significant biological activity in modulating autophagy processes, making it a valuable tool for research into autophagy-related diseases, such as KRAS-mutant lung cancer and glioblastoma. Its specificity for ULK1 allows for targeted studies in cancer biology and therapeutic development.

SR-17398 is a selective inhibitor of Unc-51-Like Kinase 1 (ULK1), exhibiting an IC50 value of 22.4 μM. Inhibition of ULK1 by SR-17398 has been shown to impact autophagy and cellular metabolism, making it a valuable tool for researchers studying these processes. This compound is applicable in research investigating the role of ULK1 in various diseases, including cancer and neurodegeneration.