Stereochemistry | ACHIRAL |
Molecular Formula | C9H10N6O |
Molecular Weight | 218.2153 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=C(\N=N\C2=CC=C(O)C=C2)C(N)=NN1
InChI
InChIKey=AYZRKFOEZQBUEA-OUKQBFOZSA-N
InChI=1S/C9H10N6O/c10-8-7(9(11)15-14-8)13-12-5-1-3-6(16)4-2-5/h1-4,16H,(H5,10,11,14,15)/b13-12+
CAN-508 is an ATP-competitive inhibitor of cyclin-dependent kinase 9 (Cdk9; IC50 = 350 nM) and moderate inhibitor of similar enzymes including Cdk2-cyclin E. In the HT-29 cancer cell line, CAN-508 was observed to attenuate the frequency of the S-phase. Other CAN-508 effects were shown to involve inhibition of mRNA synthesis, induction of p53, inhibition of IL-6 signaling and reduced phosphorylation of both retinoblastoma protein and RNA polymerase II at the C-terminal domain. CAN-508 has been observed to be an effective antitumor and antimetastatic agent by disrupting TNFα signaling. CAN-508 is an inhibitor of Cdk4, cyclin D1 and p70 S6 Kinase. CAN508 inhibits endothelial cell migration and tube formation. In addition, it reduces phosphorylation of the C-terminus of RNA polymerase II and inhibits mRNA synthesis in endothelial cells, in accordance with previous observations that it has high selectivity towards the positive transcriptional regulator P-TEFb. Moreover, CAN-508 reduces expression of vascular endothelial growth factor by several human cancer cell lines. The findings suggest that P-TEFb may be an attractive target for anti-angiogenic therapy.
Approval Year
PubMed
Patents
Sample Use Guides
In xenograft mouse models, CAN-508 (60 mg/kg/dayx10 days) caused 50.8% reduction in xenograft tumors as compared to control on post-treatment day 21.
Route of Administration:
Intraperitoneal