2. Signaling Pathways
  3. Autophagy
  4. ULK
  5. ULK1 Isoform

ULK1

ULK1 is a serine/threonine kinase and a key initiator of mammalian autophagy, functioning near the apex of a nutrient-sensitive regulatory pathway[1]. Mechanistically, AMPK binds ULK1 and supports ULK1-mediated autophagy, while mTORC1 negatively regulates the ULK1 autophagic complex through phosphorylation-dependent control[2][3]. During starvation, ULK1 links cellular energy sensing to downstream autophagy machinery, including ATG13, FIP200/RB1CC1, ATG101, ATG14L, VPS34, and phagophore formation[3][4]. In disease models, altered ULK1 signaling has been connected with prostate cancer progression, prion infection, clear cell renal cell carcinoma, cardiomyocyte oxidative injury, and pathogen-related autophagy[5][6][7][8][9]. Compared with ULK2, ULK1 shows strong functional overlap in nutrient-starvation autophagy, because combined ULK1/ULK2 loss disrupts autophagy activation more clearly than single loss[10]. Compared with ULK3, ULK1 remains part of the canonical mTOR-AMPK autophagy axis, whereas ULK3 can support mTOR-insensitive autophagic flux in BIN1-deficient hippocampal neurons[11]. For experimental applications, ULK1 pathway modulation can be studied with AMPK activators, mTOR inhibitors, deubiquitinase inhibitor WP1130, and pathway inhibitors targeting CAMKK2-AMPK-ULK1 signaling[2][5][12].

References:

ULK1 Related Products (28):

Cat. No. Product Name Effect Purity
  • HY-16966
    SBI-0206965
    		Inhibitor 99.92%
    SBI-0206965 is a potent, selective and cell permeable autophagy kinase ULK1 inhibitor with IC50s of 108 nM for ULK1 kinase and 711 nM for the highly related kinase ULK2. SBI-0206965 is also an AMPK inhibitor that can paradoxically increase Thr172 phosphorylation.
  • HY-13018
    MRT67307
    		Inhibitor 99.56%
    MRT67307 is a dual inhibitor of the IKKε and TBK-1 with IC50s of 160 and 19 nM, respectively. MRT67307 also inhibits ULK1 and ULK2 with IC50s of 45 and 38 nM, respectively. MRT67307 also blocks autophagy in cells.
  • HY-100006
    MRT68921
    		Inhibitor 98.09%
    MRT68921 is a potent NUAK1/ULK1 dual inhibitor. MRT68921 inhibits ULK1 and ULK2 with IC50 values of 2.9 nM and 1.1 nM, respectively. MRT68921 can block cells autophagy and kill tumor cells by breaking the balance of oxidative stress signals. MRT68921 can inhibit cell proliferation and induce ROS production and apoptosis. MRT68921 can be used for the research of cancer, such as breast cancer.
  • HY-114490
    ULK-101
    		Inhibitor 99.91%
    ULK-101 is a potent and selective ULK1 inhibitor, with IC50 values of 1.6 nM and 30 nM for ULK1 and ULK2, respectively. ULK-101 suppresses autophagy and sensitizes cancer cells to nutrient stress.
  • HY-160699
    DCC-3116
    		Inhibitor 99.84%
    DCC-3116 is an orally active ULK1/2 inhibitor. DCC-3116 can inhibit autophagy in lung cancer cells by inhibiting KRASG12C signaling, thereby inhibiting the proliferation of lung cancer cells and exerting anti-cancer effects.
  • HY-181062
    VWK147
    		Inhibitor
    VWK147 is a second-generation HSP90 C-terminal domain (CTD) inhibitor. VWK147 targets the CTD dimerization interface, prevents HSP90 CTD dimerization, disrupts co-chaperone PPID binding to HSP90 CTD, and inhibits HSP90 chaperone function dependent on dimerization. VWK147 reduces protein levels of HSP90 client proteins ULK1, RIPK1, and CDK4 without inducing a heat shock response. VWK147 induces cell death, including apoptosis, in Cisplatin (HY-17394)-sensitive and -resistant urothelial carcinoma cells. VWK147 induces LC3-II accumulation, inhibits autophagosome-lysosome fusion to block canonical autophagy, and induces non-canonical LC3 lipidation independent of ULK1 and PIK3C3 complexes. VWK147 can be used for the research of urothelial carcinoma.
  • HY-181742
    ULK1/2-IN-1
    		Inhibitor
    ULK1/2-IN-1 is a tissue-targeted ULK1/2 inhibitor conjugated to the RGR (CRGRRST) tumor neovasculature-homing peptide. ULK1/2-IN-1 mediates autophagy inhibition and induces cytotoxicity in endothelial cells. ULK1/2-IN-1 can be used for the research of tumor-targeted autophagy inhibitors.
  • HY-186224
    GW296115
    		Inhibitor
    GW296115 is a multi-target inhibitor with the following IC50 values against its targets: 8.4 nM for BRSK2, 21 nM for BRSK1, 1.8 μM for PDGFRβ, 5.5 nM for STK17B/DRAK2, 28 nM for DRAK1, 20 nM for PHKG1, and 89 nM for DCAMKL3. GW296115 downregulates the phosphorylation of S317 site on ULK1 and S351 site on P62, which are AMPK substrates driven by BRSK2. GW296115 does not alter the phosphorylation level of AMPK at T172, reduces nutrient deprivation-mediated Autophagy and autophagosome formation, and enhances Apoptosis. GW296115 exhibits anticancer activity against triple-negative breast cancer. GW296115 is applicable for breast cancer-related research.
  • HY-100006A
    MRT68921 dihydrochloride
    		Inhibitor 99.67%
    MRT68921 dihydrochloride is a potent NUAK1/ULK1 dual inhibitor. MRT68921 dihydrochloride inhibits ULK1 and ULK2 with IC50 values of 2.9 nM and 1.1 nM, respectively. MRT68921 dihydrochloride can block cells autophagy and kill tumor cells by breaking the balance of oxidative stress signals. MRT68921 dihydrochloride can inhibit cell proliferation and induce ROS production and apoptosis. MRT68921 dihydrochloride can be used for the research of cancer, such as breast cancer.
  • HY-124729
    BL-918
    		Activator 99.72%
    BL-918 is an orally active UNC-51-like kinase 1 (ULK1) activator with an EC50 of 24.14 nM. BL-918 exerts its cytoprotective autophagic effect by targeting ULK complex. BL-918 has the potential for Parkinson’s disease (PD) treatment.
  • HY-101923B
    LYN-1604 dihydrochloride
    		Activator 99.55%
    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).
  • HY-101923
    LYN-1604
    		Activator 99.47%
    LYN-1604 is a potent UNC-51-like kinase 1 (ULK1) activator (EC50=18.94 nM) for the research of triple negative breast cancer (TNBC).
  • HY-137742
    SBP-7455
    		Inhibitor 98.01%
    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. SBP-7455 potently inhibits ULK1/2 enzymatic activity and can be used for triple-negative breast cancer (TNBC) research.
  • HY-137506
    XST-14
    		Inhibitor 99.26%
    XST-14 is a potent, competitive and highly selective ULK1 inhibitor with an IC50 of 26.6 nM. XST-14 induces autophagy inhibition by reducing the phosphorylation of the ULK1 downstream substrate. XST-14 induces apoptosis in hepatocellular carcinoma (HCC) cells and has antitumor effects.
  • HY-148061
    DB1113
    		99.86%
    DB1113 (Example 24) is a bifunctional compound targeted protein degradation of kinases. DB1113 degrades ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2, and ULK1. DB1113 can be used for research of disease or disorder mediated by aberrant kinase activity.
  • HY-179089
    SBP-1750
    		Inhibitor 98.05%
    SBP-1750 is an orally active ULK inhibitor and an ATG13 degrader. SBP-1750 strongly inhibits ULK1/2 activity, with IC50 values of 8 and 50 nM, respectively. SBP-1750 induces ATG13 degradation, with an EC50 value of 114 nM. SBP-1750 can inhibit autophagy in cancer cells and induce cell death. SBP-1750 can be used in cancer research, such as for pancreatic cancer.
  • HY-143466
    ULK1-IN-2
    		Inhibitor 98.34%
    ULK1-IN-2 (compound 3s) is a potent ULK1 inhibitor. ULK1-IN-2 shows highest cytotoxic effect against cancer cell lines, with IC50 of 1.94 μM in A549. ULK1-IN-2 can induce apoptosis and simultaneously block autophagy, and can be used to study NSCLC (Non-small cell lung cancer).
  • HY-148063
    DB0614
    DB0614 is a PROTAC based on Cereblon ligand, which is a selective and potent targeted protein degrader of NEK9 inhibitor. DB0614 can degrade ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2 and ULK1. DB0614 can be used for research of disease or disorder mediated by aberrant kinase activity.(Blue: Thalidomide-4-OH (HY-103596), Black: linker, Pink: FLT3-IN-17 (HY-148070))
  • HY-101923A
    LYN-1604 hydrochloride
    		Activator
    LYN-1604 hydrochloride is a potent UNC-51-like kinase 1 (ULK1) activator (EC50=18.94 nM) for the research of triple negative breast cancer (TNBC).
  • HY-13018A
    MRT67307 hydrochloride
    		Inhibitor
    MRT67307 hydrochloride is a dual inhibitor of the IKKε and TBK-1 with IC50s of 160 and 19 nM, respectively. MRT67307 hydrochloride also inhibits ULK1 and ULK2 with IC50s of 45 and 38 nM, respectively. MRT67307 hydrochloride also blocks autophagy in cells.
Cat. No. Product Name / Synonyms Application Reactivity