Physicochemical Properties
| Molecular Formula | C26H36F3N7O2 |
| Molecular Weight | 535.60 |
| Exact Mass | 535.288 |
| CAS # | 2543673-19-2 |
| PubChem CID | 155269708 |
| Appearance | Solid powder |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 38 |
| Complexity | 738 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | CNBTYICEJGEABG-UHFFFAOYSA-N |
| 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) |
| 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 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | ULK1 ULK2 KRas G12C |
| 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]. |
| 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]. |
| 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%). |
| References |
[1]. Inhibition of ULK1/2 and KRAS G12C controls tumor growth in preclinical models of lung cancer. bioRxiv [Preprint]. 2024 Feb 8:2024.02.06.579200. |
| Additional Infomation | Inlexisertib is an orally bioavailable inhibitor of the serine/threonine-protein kinase ULK 1 and 2, with potential antineoplastic activity. Upon oral administration, inlexisertib targets and binds to ULK1/2. This inhibits cancer autophagy, which mutant RAS cancer cells use for their survival, and results in tumor cell death. ULK1/2 mediates the autophagocytotic process and is often upregulated in cancers, especially in mutant RAS cancers. Autophagy plays a key role in a tumor cell proliferation and survival, and mediates tumor cell resistance. |
Solubility Data
| Solubility (In Vitro) | DMSO : 140 mg/mL (261.39 mM; with sonication) |
| 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 |