CH7057288

• CAS: 2095616-82-1
• Catalog Number: ACM2095616821
• Category: Inhibitors
• Molecular Weight: 569.68
• Molecular Formula: C32H31N3O5S
• Description: CH7057288 is a selective TRK inhibitor that may be useful in inhibiting TRK fusion-positive cancer cell growth. TRK receptor tyrosine kinases are expressed as fusion proteins encoded by various fusion genes across a wide variety of cancer types, including lung and colorectal cancer.
• Synonyms: CH7057288; CH-7057288; CH 7057288
• IUPAC Name: N-(tert-butyl)-2-((6,6-dimethyl-8-(methylsulfonamido)-11-oxo-6,11-dihydronaphtho[2,3-b]benzofuran-3-yl)ethynyl)-6-methylisonicotinamide
• Canonical SMILES: CS(NC1=CC=C2C(C(C)(C)C(OC3=CC(C#CC4=NC(C)=CC(C(NC(C)(C)C)=O)=C4)=CC=C35)=C5C2=O)=C1)(=O)=O
• InChI: 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)
• InChI Key: DCGOHGQJHJXBGW-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: CH7057288 is a potent and selective TRK inhibitor with IC50 values of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB, and TRKC respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 67.47; H, 5.49; N, 7.38; O, 14.04; S, 5.63
• Exact Mass: 569.1984
• HS Tariff Code: 2934.99.03.00
• In Vitro Activity: CH7057288's cellular inhibition of TRK activity was investigated using three TRK fusion-positive cancer cell lines. CH7057288 potently inhibited autophosphorylation of TRK in a dose-dependent manner. As for downstream signaling of TRK fusion, phosphorylation of the PLCγ1, MAPK, and Akt pathways were investigated, since these three pathways are known to be involved in TRK. CH7057288 suppressed phosphorylation of PLCγ1 and ERK, although suppression levels varied somewhat in different cell lines, and Akt phosphorylation was slightly inhibited in CUTO-3 but strongly suppressed in KM12-Luc and MO-91. These observations indicate that CH7057288 has inhibitory activity to TRK and blocks TRK fusion-mediated signaling in cells.; Reference: Mol Cancer Ther. 2018 Dec;17(12):2519-2529. https://pubmed.ncbi.nlm.nih.gov/30242093/
• In Vivo Activity: CH7057288 was tested in an intracranial implantation model of CUTO-3-Luc that mimics metastasis to the central nervous system (CNS). Luminescence was reduced after CH7057288 treatment but was enhanced in the vehicle control group, indicating regression of intracranial tumors by the compound. When event-free survival was assessed, survival was significantly prolonged by 30-day CH7057288 treatment compared with vehicle treatment. The CH7057288-treated animals survived throughout the treatment without events, in contrast to the control mice, of which more than half were removed from the experiment by Day 26. Mean survival of the treated group reached 67 days after treatment initiation. These tests collectively show that CH7057288 demonstrated potent in vivo antitumor activity, with reasonable pharmacodynamic response in subcutaneous xenograft models and prolonged event-free survival in an intracranial model.; Reference: Mol Cancer Ther. 2018 Dec;17(12):2519-2529. https://pubmed.ncbi.nlm.nih.gov/30242093/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).