CG428

CG428 is a potent and selective tropomyosin receptor kinase (TRK) PROTAC degrader that has anti-tumor activity. CG428 reduces levels of the tropomyosin 3 (TPM3) -TRKA fusion protein in KM12 colorectal carcinoma cells (DC50 = 0.36 nM) and inhibits downstream PLCγ1phosphorylation (IC50 = 0.33 nM) . CG428 has a higher binding affinity for TRKA than TRKB and TRKC (Kd = 1 nM, 28 nM and 4.2 nM, respectively) . In addition, CG428 effectively inhibits KM12 cell growth (IC50 = 2.9 nM) [1]. (Pink: TRK inhibitor (HY-118271) ; Black: linker (HY-W067489) ; Blue: CRBN Ligand (HY-41547) )

Product Specifications

CAS Number

[2412055-93-5]

UNSPSC

12352005

Target

PROTACs; Trk Receptor

Type

Reference compound

Related Pathways

Neuronal Signaling; PROTAC; Protein Tyrosine Kinase/RTK

Applications

Cancer-Kinase/protease

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/cg428.html

Purity

98.26

Solubility

DMSO : 100 mg/mL (ultrasonic)

Smiles

O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3NCCOCCC(N4CCN(C5=NC(C6=CN=C7C=CC(N8[C@@H](C9=CC=CC(F)=C9)CCC8)=NN76)=CC=C5)CC4)=O)=O

Molecular Formula

C43H43FN10O6

Molecular Weight

814.86

References & Citations

[1]Chen L, et al. Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders. J Med Chem. 2020 Dec 10;63 (23) :14562-14575.