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| 5mg |
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| 25mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
LY03009120 (DP4978; LY-3009120; LY-03009120; DP-4978) is a novel and potent pan-Raf inhibitor with potential anticancer activity. It inhibits A-raf, B-raf, and C-raf with IC50 values of 44 nM, 37 nM, and 42 nM, respectively. It demonstrated activities against BRaf or Ras mutant tumor cells and has strong antitumor activity. In cells with activating mutations of BRaf or KRas, it binds to ARaf, BRaf, and CRaf isoforms with comparable affinity. In multiple xenograft models with mutations in BRaf, NRas, or KRas, LY3009120 exhibits anti-tumor activity by inhibiting MEK phosphorylation and cell proliferation in vitro.
| Targets |
C-Raf (IC50 = 4.3 nM); BRAF(V600E) (IC50 = 5.8 nM); BRAF WT (IC50 = 15 nM)
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| ln Vitro |
LY3009120 has an IC50 of 9.2 and 220 μM, respectively, and inhibits the growth of the A375 and HCT116 cells. KDR tyrosine kinase is inhibited by LY3009120 with an IC50 of 3.9 μM. [1]
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| ln Vivo |
LY3009120 (15 or 30 mg/kg, p.o.) exhibits a dose-dependent tumor growth inhibition in rats with BRAF V600E ST019VR PDX tumors. Single-dose oral administration of LY3009120 (3 to 50 mg/kg, p.o.) to naked rats bearing A375 xenografts results in a dose-dependent inhibition of phospho-ERK, with an effective dose (EC50) of 4.36 mg/kg and an effective plasma concentration (EC50) of 68.9 ng/mL or 165 nM. [1]
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| Enzyme Assay |
In A375 cell lysates, compounds are screened using the ATP-based probe at a concentration of 5 µM. Micromolar units are used to report IC50 values. After being resuspended in four volumes of lysis buffer (25 mM Tris pH 7.6, 150 mM NaCl, 1% CHAPS, 1% Tergitol NP-40 type, and 1% v/v phosphatase inhibitor cocktail II), cell pellets are sonicated using a tip sonicator and then thoroughly homogenized. By centrifuging lysates for 30 minutes at 100,000 g, lysates are removed. The cleared lysates are filtered through a 0.22 μM syringe filter and gel filtered into reaction buffer (20 mM Hepes pH 7.8, 150 mM NaCl, 0.1% triton X-100, and 1% v/v phosphatase inhibitor cocktail II). After that, MnCl2 is added to the lysate until it reaches a final concentration of 20 mM before the inhibitor treatment and probe labeling. The final inhibitor concentrations used to calculate IC50 are 10, 1, 0, and 0.1 μM. At 1,000, 100, 10, and 1 μM ATP, ATP competition experiments are conducted. Every inhibitor treatment is carried out at room temperature.
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| Cell Assay |
In a nutshell, cells are grown in DMEM high glucose enriched with 10% characterized fetal bovine serum and 1% penicillin/streptomycin/L-glutamine at 37°C, 5% CO2, and 95% humidity. Up until 70–95% confluency, cells are permitted to grow. A 384-well black clear bottom plate is filled with test compound serially diluted. In 50 μL of complete growth medium, 625 cells are added to each well. At 37°C, 5% CO2, and 95% humidity, plates are incubated for 67 hours. The plates are then incubated for an additional 5 hours at 37°C, 5% CO2, and 95% humidity, with 10 L of a 440 M solution of resazurin in PBS being added to each well.
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| Animal Protocol |
Briefly, female NIH nude rats receive a subcutaneous injection of 5×106 to 10×106 tumor cells in a 1:1 Matrigel mixture (0.2 mL total volume). Animals are randomly divided into groups of eight for efficacy studies once tumors reach the desired size of about 300 mm3. With the prescribed dosage schedules, medications (LY3009120 or PLX4032) are given orally (gavage) in a 0.6-mL volume of vehicle. The development of the tumor and body weight are tracked over time to assess effectiveness and potential toxicity.
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| References |
| Molecular Formula |
C23H29FN6O
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| Molecular Weight |
424.51
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| Exact Mass |
424.24
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| Elemental Analysis |
C, 65.07; H, 6.89; F, 4.48; N, 19.80; O, 3.77
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| CAS # |
1454682-72-4
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| Related CAS # |
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| Appearance |
Light yellow solid powder
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| SMILES |
CC1=CC(=C(C=C1C2=C(N=C3C(=C2)C=NC(=N3)NC)C)NC(=O)NCCC(C)(C)C)F
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| InChi Key |
HHCBMISMPSAZBF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H29FN6O/c1-13-9-18(24)19(29-22(31)26-8-7-23(3,4)5)11-16(13)17-10-15-12-27-21(25-6)30-20(15)28-14(17)2/h9-12H,7-8H2,1-6H3,(H2,26,29,31)(H,25,27,28,30)
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| Chemical Name |
1-(3,3-dimethylbutyl)-3-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.89 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 2: 0.5% CMC Na: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3557 mL | 11.7783 mL | 23.5566 mL | |
| 5 mM | 0.4711 mL | 2.3557 mL | 4.7113 mL | |
| 10 mM | 0.2356 mL | 1.1778 mL | 2.3557 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02014116 | Terminated | Drug: LY3009120 capsule | Neoplasms Melanoma |
Eli Lilly and Company | November 26, 2013 | Phase 1 |
Products are for research use only; We do not sell to patients
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