Alectinib

Details:

Boiling point     722.5±60.0 °C(Predicted)
density     1.28
pka    13.70±0.40(Predicted)

Bioactivity    Alectinib (CH5424802) is an efficient ALK inhibitor. Its IC50 is 1.9nM and it is sensitive to the L1196M mutant, which is highly selective for ALK than PF-02341066, NVP-TAE684 and PHA-E429.
Solubility    In vitro (25 ° C): DMSO-2 mg/mL heating (4.14 mM); Water-<1 mg/mL (<1 mM); Ethanol-<1 mg/mL (<1 mM)
In vivo (25 ° C): 30% PEG 400/0.5% Tween 80/5% propylene glycol-30 mg/mL.
In vitro    Alteinib (CH5424802) can act on ALK and it is ATP-competitive, with a dissociation constant (KD) of 2.4 nM. CH5424802 has a strong inhibitory effect on ALK and L1196M. The Ki is 0.83 and 1.56 nM, respectively. CH5424802 acts on NCI-H2228 NSCLC cells expressing EML4-ALK, inhibiting ALK autophosphorylation. CH5424802 can also inhibit STAT3 and AKT, rather than ERK1/2 phosphorylation. CH5424802 completely inhibited Tyr705, a phosphorylation site of STAT3. CH5424802 preferentially acted on NCI-H2228 cells expressing EML4-ALK without acting on negative NSCLC cell lines that contains ALK, including monolayer cultured HCC827 cells (deletion of EGFR exon19), A549 cells (KRAS mutations) or NCI-H522 cells (EGFR wild type, KRAS wild type, and ALK wild type). CH5424802 acted on NCI-H2228 spherocytes, causing apoptosis-caspase-3/7-like activation. CH5424802 cam inhibit the growth of two lymphoma cells, KARPAS-299 and SR, containing NPM-ALK fusion protein and does not affect the growth of HDLM-2 lymphoma cells without ALK fusion. CH5424802 acted on KARPAS-299 with highly targeted selectivity and stronger antiproliferative activity. When CH5424802 inhibits KAPRAS-299, the IC50 is 3 nM. When inhibit KDR, IC50 was 1.4 μM. The metabolic stability of CH5424802 was high.