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Details

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
Structure of CAN-508

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+

HIDE SMILES / InChI

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
20.0 µM [IC50]
0.35 µM [IC50]
13.5 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
CAN-508 shows antiproliferative effects (IC50 values are 33, 49, 64 and 62 uM for MCF7, HOS, G361, and K562 cells respectively).