| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ULK1 ULK2 KRas G12C
ULK1 and ULK2 (serine/threonine kinases that initiate autophagy). DCC‑3116 is a selective inhibitor of ULK1 and ULK2, blocking the initiation step of autophagy. |
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| ln Vitro |
DCC-3116 (100 nM, 72 h) inhibited the proliferation of NCI-H2122 and Calu-1 cells and reduced the expression of pS318-ATG13 when used alone, and had a synergistic effect when used in combination with Sotorasib (HY-114277) [1].
In cell‑free enzymatic assays, DCC‑3116 inhibits ULK1 and ULK2 activity. It is a potent and selective ULK1/2 inhibitor. In cellular assays, DCC‑3116 (0.1‑10 uM) inhibits both basal and sotorasib‑induced autophagy in KRAS G12C‑driven lung cancer cell lines, leading to reduced cell proliferation. Inhibition of autophagy may enhance the efficacy of KRAS G12C inhibitors such as sotorasib. |
| ln Vivo |
DCC-3116 (3 or 30 mg/kg per day for 56 days, po and pi) alone or in combination with sotorasib (HY-114277) can inhibit tumor growth in a mouse model of NSCLC lung cancer [1].
In vivo, DCC‑3116 demonstrates anti‑tumor activity in KRAS‑mutant lung cancer xenograft models. As an orally active ULK1/2 inhibitor, it can be administered to mice bearing KRAS G12C‑driven tumors. When combined with a KRAS G12C inhibitor (e.g., sotorasib), DCC-3116 enhances the anti‑tumor efficacy by blocking the protective autophagy response. |
| Enzyme Assay |
A general cell‑free protocol for ULK1 inhibition: A radiometric or time‑resolved fluorescence resonance energy transfer (TR‑FRET) kinase assay is used. Recombinant active ULK1 (10 nM) is incubated with a peptide substrate (e.g., ATG13 peptide) and ATP in kinase buffer with varying concentrations of DCC‑3116 (0.1‑1000 nM). The reaction is incubated at 30degC for 30‑60 minutes. The phosphorylated product is detected, and the IC50 is calculated. A similar assay is performed for ULK2.
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| Cell Assay |
A general cellular protocol for DCC‑3116: KRAS G12C‑mutant lung cancer cells (e.g., NCI‑H358, MIA PaCa‑2) are seeded in 6‑well plates. Cells are treated with DCC‑3116 at concentrations of 0.1, 0.5, 1, 5, 10 uM for 24‑48 hours. Autophagy is assessed by measuring the LC3B‑II/LC3B‑I ratio and p62 degradation by Western blot. Autophagic flux is measured in the presence or absence of lysosomal inhibitors (e.g., chloroquine). For combination studies, cells are treated with DCC‑3116 (1 uM) and sotorasib (0.1‑1 uM), and cell viability is assessed by CellTiter‑Glo assay. Apoptosis is assessed by Annexin V/PI staining and cleaved PARP Western blot.
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| Animal Protocol |
Animal/Disease Models:mouse models of NSCLC lung cancer (adult mice were initiated between 6-8 weeks of age) [1]
Doses: 3 or 30 mg/kg/day for 56 days Route of Administration: p.o. and p.i Experimental Results: Inhibited mice tumor growth and improved mice survival rate, while significantly reducing mice body weight (>20%). A general animal protocol for DCC‑3116: Female BALB/c nude mice are subcutaneously implanted with KRAS G12C‑mutant lung cancer cells (e.g., NCI‑H358). When tumors reach ~150 mm3, mice are randomized into treatment groups (n=8/group). DCC‑3116 is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween‑80, 45% saline) and administered via oral gavage at doses of 10, 30, and 100 mg/kg once daily for 21 days. For combination studies, DCC‑3116 is administered with sotorasib (10 mg/kg daily). Tumor volume is measured twice weekly. At the end of the study, tumors are harvested for Western blot (LC3B, p62, cleaved PARP), IHC (Ki‑67, LC3B), and TUNEL staining. |
| ADME/Pharmacokinetics |
General PK protocol for DCC‑3116: Male Sprague‑Dawley rats are administered DCC‑3116 via oral gavage (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg). Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours. Plasma concentrations are quantified by LC‑MS/MS. PK parameters (Cmax, Tmax, AUC, t1/2, clearance, Vd, and oral bioavailability) are calculated.
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| References | |
| Additional Infomation |
Inlexisertib is an orally bioavailable inhibitor of serine/threonine protein kinases ULK1 and ULK2 with potential antitumor activity. After oral administration, inlexisertib targets and binds to ULK1/2. This inhibits autophagy in cancer cells, a mechanism essential for the survival of RAS-mutant cancer cells, ultimately leading to tumor cell death. ULK1/2 mediates autophagy, and its expression is typically upregulated in various cancers, particularly RAS-mutant cancers. Autophagy plays a crucial role in tumor cell proliferation and survival and mediates tumor cell drug resistance.
DCC‑3116 (Inlexisertib) is an ATP‑competitive inhibitor of ULK1/2. The molecular formula is C26H36F3N7O2, and the molecular weight is 535.61 g/mol. The compound is soluble in DMSO at 100 mg/mL (186.7 mM). It has been investigated in clinical trials as a single agent and in combination with sotorasib (Lumakras) for the treatment of KRAS G12C‑mutant solid tumors, including non‑small cell lung cancer (NSCLC) and colorectal cancer. DCC‑3116 was discovered by Deciphera Pharmaceuticals. |
| Molecular Formula |
C26H36F3N7O2
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|---|---|
| Molecular Weight |
535.60
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| Exact Mass |
535.288
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| CAS # |
2543673-19-2
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| PubChem CID |
155269708
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| Appearance |
Solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
38
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| Complexity |
738
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1=C(C=CC(=C1)N2CCN(CC2)C)NC3=NC=C(C(=N3)NCCCN4CCOCCC4=O)C(F)(F)F
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| InChi Key |
CNBTYICEJGEABG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H36F3N7O2/c1-3-19-17-20(35-12-10-34(2)11-13-35)5-6-22(19)32-25-31-18-21(26(27,28)29)24(33-25)30-8-4-9-36-14-16-38-15-7-23(36)37/h5-6,17-18H,3-4,7-16H2,1-2H3,(H2,30,31,32,33)
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| Chemical Name |
4-[3-[[2-[2-ethyl-4-(4-methylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]propyl]-1,4-oxazepan-5-one
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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) |
DMSO : 140 mg/mL (261.39 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.5 mg/mL (6.53 mM)(saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution This solution produces a clear solution of ≥ 3.5 mg/mL (saturation unknown).
For example, if 1 mL of working solution, add 100 μL of 35.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make up to 1 mL. *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.5 mg/mL (6.53 mM)(saturation unknown) in 10% DMSO 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution This protocol will produce a clear solution of ≥ 3.5 mg/mL (saturation unknown). . For example, if 1 mL of working solution, add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix. *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 3.5 mg/mL (6.53 mM)(saturation unknown) in 10% DMSO 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution, add 100 μL of 35.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8671 mL | 9.3353 mL | 18.6706 mL | |
| 5 mM | 0.3734 mL | 1.8671 mL | 3.7341 mL | |
| 10 mM | 0.1867 mL | 0.9335 mL | 1.8671 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05957367
Conditions:GISTLink: https://clinicaltrials.gov/ct2/show/NCT04892017
Conditions:Non-Small Cell Lung Cancer|Advanced Solid Tumor|Metastatic Solid TumorProducts are for research use only; We do not sell to patients
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