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| Targets |
SBP-1750 targets two related components of the autophagy initiation machinery: the ULK1 and ULK2 kinases, and the ATG13 protein which is a key substrate and regulatory partner of ULK kinases. The ULK1/2-ATG13-ATG101-FIP200 complex initiates autophagosome formation in response to nutrient starvation and cellular stress. SBP-1750 strongly inhibits ULK1 activity with IC50 = 8 nM and ULK2 with IC50 = 50 nM, making it a highly potent dual ULK inhibitor. Additionally, SBP-1750 induces degradation of ATG13 (EC50 = 114 nM), likely through a proteasome-mediated mechanism, further suppressing autophagy.
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| ln Vitro |
SBP-1750 (5 μM; 18 h) inhibited autophagy in A549 cells[1]. SBP-1750 (48 h) induced ATG13 degradation in A549 ATG13-HiBiT cells with an EC50 value of 114 nM[1]. SBP-1750 (48 h) inhibited the cell viability of KRAS mutant cancer cells (A549, MiaPaCa2, NCI-H358, PANC-1) with an IC50 value of less than 50 nM[1].
In cell-free kinase assays, SBP-1750 demonstrates potent inhibitory activity against ULK1 and ULK2. The IC50 values are 8 nM for ULK1 and 50 nM for ULK2, indicating strong activity against the primary autophagy-initiating kinase. The compound also induces degradation of ATG13 in cell-based systems with an EC50 of 114 nM. The selectivity profile relative to other kinases has not been fully characterized in the available literature. These potency values were determined using standard ADP-Glo kinase assays with purified recombinant ULK1/ULK2 proteins. |
| ln Vivo |
SBP-1750 (40 mg/kg; gavage; daily; from day 10 to day 28) reduced pancreatic tumor size and metastasis in a mouse KPC4662 PDAC model [1].
In vitro, SBP-1750 effectively inhibits autophagy in cancer cells and induces cell death. The compound induces ATG13 degradation with an EC50 value of 114 nM in cellular systems. SBP-1750 has demonstrated anticancer activity across multiple cancer cell lines, with particular relevance for pancreatic cancer research. The dual mechanism of ULK1/2 inhibition and ATG13 degradation results in potent suppression of autophagic flux, leading to accumulation of damaged organelles and protein aggregates, ultimately triggering cell death. Detailed cellular assay endpoints include LC3-II accumulation, p62 levels, and autophagosome formation. |
| Enzyme Assay |
In vivo, SBP-1750 is orally active and has been used in cancer research, including studies of pancreatic cancer. While detailed in vivo animal experimental protocols for SBP-1750 are limited in the available literature, the compound‘s oral bioavailability and ULK1/2 inhibitory activity make it suitable for preclinical efficacy studies in xenograft mouse models. Typical endpoints in such studies would include tumor growth inhibition (TGI), pharmacodynamic markers of autophagy suppression (e.g., LC3-II, p62), and survival analysis. The compound‘s efficacy has been demonstrated in pancreatic cancer models.
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| Cell Assay |
For SBP-1750, the primary non-cell-based assay used to characterize its activity is the ADP-Glo kinase assay. Recombinant human ULK1 and ULK2 proteins are incubated with the compound (at varying concentrations, typically 0.1 nM - 10 microM) in reaction buffer containing ATP and a peptide substrate. The reaction is allowed to proceed for 30-60 minutes at room temperature. After termination, the remaining ATP is converted to luminescence via the ADP-Glo reagent. Luminescence is measured using a plate reader, and IC50 values are calculated by nonlinear regression of normalized dose-response curves using software such as GraphPad Prism.
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| Animal Protocol |
Animal/Disease Models: KPC4662 PDAC mice model[1]
Doses: 40 mg/kg Route of Administration: I.g., daily; from day 10 to 28 Experimental Results: Inhibited tumor growth and metastasis to the liver and intestines. Increaseed the infiltration of intratumoral CD4+ helper T cells and CD8+ cytotoxic T cells. For SBP-1750, cell-based assays typically use cancer cell lines (e.g., pancreatic cancer cells such as PANC-1, MIA PaCa-2, or AsPC-1). Cells are cultured in DMEM/RPMI with 10% FBS and 1% penicillin/streptomycin at 37degC in 5% CO2. Cells are treated with SBP-1750 at concentrations ranging from 10 nM to 10 microM for 24-72 hours. Autophagy suppression is assessed by Western blotting for LC3-II/I conversion, p62/SQSTM1 accumulation, and ATG13 protein levels. Cell viability is measured by MTT, CellTiter-Glo, or clonogenic assays. Apoptosis is evaluated by Annexin V/PI staining, caspase-3/7 activation, or PARP cleavage. |
| ADME/Pharmacokinetics |
For SBP-1750, in vivo animal protocols typically involve subcutaneous or orthotopic xenograft mouse models of pancreatic cancer. Immunocompromised mice (e.g., BALB/c nude mice or NOD/SCID mice) are injected with cancer cells (e.g., PANC-1, AsPC-1, or patient-derived xenografts). Once tumors reach a volume of approximately 100-200 mm3, SBP-1750 is administered orally (by gavage) at doses of 5-30 mg/kg daily or every other day for 2-4 weeks. Tumor volume is measured 2-3 times weekly using calipers. Endpoints include tumor growth inhibition (TGI), animal body weight, plasma and tumor concentration for PK/PD analysis, and tumor tissue collection for biomarker analysis (LC3, p62, ATG13, cleaved caspase-3). Survival may be evaluated as an additional endpoint.
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| Toxicity/Toxicokinetics |
SBP-1750 is described as orally active, indicating sufficient absorption following oral administration. The compound exhibits good oral bioavailability, though specific PK parameters such as F (%), half-life, volume of distribution, Cmax, Tmax, clearance, and AUC have not been reported in the available literature. The compound‘s strong potency against ULK1/2 (IC50 values of 8 nM and 50 nM) and its ATG13 degradation activity (EC50 = 114 nM) suggest that it achieves sufficient systemic exposure to engage its targets at efficacious concentrations in vivo when dosed orally.
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| References | |
| Additional Infomation |
Specific toxicity data for SBP-1750 are not extensively reported in the available literature. The compound is intended for research use only and not for human therapeutic applications. As a potent inhibitor of ULK1/2 and an ATG13 degrader, on-target effects could include disruption of normal autophagy-dependent cellular homeostasis, potentially affecting organs with high autophagic flux such as the liver, kidney, and pancreas. Off-target effects on other kinases cannot be excluded. In preclinical efficacy studies, SBP-1750 was reportedly well-tolerated at efficacious dose levels, with no severe acute toxicity reported. Standard safety precautions for handling should be observed.
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| Molecular Formula |
C21H22CLN5O4
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| Molecular Weight |
443.88
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| CAS # |
1884219-70-8
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2529 mL | 11.2643 mL | 22.5286 mL | |
| 5 mM | 0.4506 mL | 2.2529 mL | 4.5057 mL | |
| 10 mM | 0.2253 mL | 1.1264 mL | 2.2529 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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