LUT014 is a novel, potent and topical B-Raf inhibitor that is a first-in-class, proprietary small molecule that enables patients to receive EGFR (Epidermal Growth Factor Receptor) Inhibitors without being interrupted by typical cutaneous side effects. Lutris-Pharma is working on LUT014 at the moment. LUT014 reduces the dermal toxicities associated with EGFR Inhibitors, thereby reducing the acneiform lesions associated with such therapy by taking advantage of the paradoxical effect of B-Raf Inhibitors.
Physicochemical Properties
| Molecular Formula | C27H19F3N8O |
| Molecular Weight | 528.487974405289 |
| Exact Mass | 528.16 |
| Elemental Analysis | C, 61.36; H, 3.62; F, 10.78; N, 21.20; O, 3.03 |
| CAS # | 2274819-46-2 |
| Related CAS # | 2274819-46-2 |
| PubChem CID | 138319775 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 6.2 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 39 |
| Complexity | 808 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | FZPYULHBUBXPIG-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C27H19F3N8O/c1-15-7-8-19-18(9-11-32-24(19)37-16-4-2-5-17(12-16)39-27(28,29)30)21(15)38-25-20(6-3-10-31-25)22-23-26(35-13-33-22)36-14-34-23/h2-14H,1H3,(H,31,38)(H,32,37)(H,33,34,35,36) |
| Chemical Name | 6-methyl-5-N-[3-(7H-purin-6-yl)pyridin-2-yl]-1-N-[3-(trifluoromethoxy)phenyl]isoquinoline-1,5-diamine |
| Synonyms | LUT 014; LUT014; LUT-014 |
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | B-Raf (IC50 = 11.7 nM); BRAF (IC50 = 14 nM); CRAF (IC50 = 23 nM) |
| References |
[1]. Novel braf inhibitors and use there of for treatment of cutaneous reactions. WO2019026065A2. |
| Additional Infomation | BRAF Inhibitor LUT014 is a topically bioavailable small molecule inhibitor of serine/threonine-protein kinase B-raf (BRAF) protein with potential chemoprotective activity. Upon topical administration, BRAF inhibitor LUT014 targets and binds BRAF and, through the paradoxical effect of BRAF inhibition, induces mitogen-activated protein kinase (MAPK) signaling, which leads to the proliferation and migration of healthy human keratinocytes. This decreases dermal toxicities associated with epidermal growth factor (EGFR) inhibitor therapy. BRAF, a member of the raf family of serine/threonine protein kinases, plays a role in the regulation of MAPK/extracellular signal-regulated kinase (ERK) signaling pathways. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~50 mg/mL (~94.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.94 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. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8922 mL | 9.4609 mL | 18.9218 mL | |
| 5 mM | 0.3784 mL | 1.8922 mL | 3.7844 mL | |
| 10 mM | 0.1892 mL | 0.9461 mL | 1.8922 mL |