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Purity: ≥98%
CH7057288 is a novel, potent and selective inhibitor of TRK (tyrosine receptor kinase) with IC50 values of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB, and TRKC respectively. In cell-free kinase tests, CH7057288 demonstrated specific inhibitory activity against TRKA, TRKB, and TRKC. It also inhibited the growth of TRK fusion-positive cell lines, but not that of TRK-negative cell lines. Significant tumor growth inhibition was seen in xenograft models of TRK fusion-positive cells that were implanted subcutaneously. Moreover, in an intracranial implantation model that replicates brain metastasis, CH7057288 significantly increased event-free survival and caused intracranial tumors to recede. In patients exhibiting disease progression following treatment with a TRK inhibitor in clinical development, resistant mutations in TRK have recently been reported. In vitro and in vivo activity levels of CH7057288 against some of the resistant mutants were comparable to those observed with wild-type TRK. In conclusion, CH7057288 shows promise as a treatment for cancers that fuse the TRK gene. Lung and colorectal cancer are among the many cancer types in which TRK receptor tyrosine kinases are expressed as fusion proteins encoded by different fusion genes. Due to their strong carcinogenic properties, these fusion proteins are considered to be promising targets for therapy.
| Targets |
TrkA (IC50 = 1.1 nM); TrkC (IC50 = 5.1 nM); TrkB (IC50 = 7.8 nM)
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| ln Vitro |
CH7057288 inhibits the growth of TRK fusion-positive cell lines, but not that of TRK-negative cell lines, and exhibits selective inhibitory activity against TRKA, TRKB, and TRKC in cell-free kinase assays. As a downstream signaling of TRK fusion, CH7057288 inhibits the E2F and mitogen-activated protein kinase (MAPK) pathways[1].
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| ln Vivo |
Subcutaneously implanted xenograft tumor models of TRK fusion-positive cells show strong in vivo inhibitory effects on tumor growth. Additionally, CH7057288 significantly induces tumor regression and enhances event-free survival in an intracranial implantation model that mimics brain metastasis. In all three models, CH7057288 induces strong tumor growth inhibition, with notable tumor regression in CUTO-3 and MO-91. Exposure to CH7057288 varies with dose. The plasma concentration decreased to about a few tenths to a hundredth of Tmax 24 hours after the dose due to the relatively short terminal half-life (3 to 5 hours)[1].
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| Cell Assay |
The indicated concentrations of CH7057288 are applied for two hours to the TRK fusion-positive cancer cell lines CUTO-3, KM12-Luc, and MO-91. Western blotting is performed after the cells have been lysed.
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| References |
| Molecular Formula |
C32H31N3O5S
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| Molecular Weight |
569.670646905899
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| Exact Mass |
569.20
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| Elemental Analysis |
C, 67.47; H, 5.49; N, 7.38; O, 14.04; S, 5.63
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| CAS # |
2095616-82-1
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| Related CAS # |
2095616-82-1
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| Appearance |
Solid powder
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| SMILES |
CC1=CC(=CC(=N1)C#CC2=CC3=C(C=C2)C4=C(O3)C(C5=C(C4=O)C=CC(=C5)NS(=O)(=O)C)(C)C)C(=O)NC(C)(C)C
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| InChi Key |
DCGOHGQJHJXBGW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H31N3O5S/c1-18-14-20(30(37)34-31(2,3)4)16-21(33-18)10-8-19-9-12-24-26(15-19)40-29-27(24)28(36)23-13-11-22(35-41(7,38)39)17-25(23)32(29,5)6/h9,11-17,35H,1-7H3,(H,34,37)
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| Chemical Name |
N-tert-butyl-2-[2-[8-(methanesulfonamido)-6,6-dimethyl-11-oxonaphtho[2,3-b][1]benzofuran-3-yl]ethynyl]-6-methylpyridine-4-carboxamide
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| Synonyms |
CH7057288; CH-7057288; CH 7057288
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| HS Tariff Code |
2934.99.03.00
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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: ~100 mg/mL (~175.5 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (4.83 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 27.5 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 | 1.7554 mL | 8.7770 mL | 17.5540 mL | |
| 5 mM | 0.3511 mL | 1.7554 mL | 3.5108 mL | |
| 10 mM | 0.1755 mL | 0.8777 mL | 1.7554 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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