1256580-46-7

Hazard Information

Questions And Answer

• 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.;

• In vivo

  The oral treatment of CH5424802 can inhibit tumor growth. This role is dose-dependent, and the ED50 is 0.46 mg/kg. CH5424802 was treated at a dose of 20 mg/kg, causing a rapid regression of the tumor, with a recurrent rate of 168%. After 11 days of treatment (at day 28), the tumor volume in each mouse was less than 30 mm3, maintaining an effective anti-tumor effect; no tumor regurgitation occurs in no drug treatment period whitin 4 weeks.The half-life and oral bioavailability for CH5424802 treated mice were 8.6 hours and 70.8%, respectively. The mean plasma levels were 1.7, 1.5, and 0.3 nM after the treatment of 6 mg/kg repeated doses for 2, 7, and 24 hours.CH5424802 treatment inhibited tumor growth.Use CH5424802 to treat KARPAS-299 and NB-1 at a dose of 20 mg/kg, and on day 20, tumor growth was inhibited by 119% and 104%.CH5424802 inhibited STAT3 phosphorylation, which is dose-dependent (2-20 mg/kg), a decrease in phosphorylation of AKT was observed in the xenografts treated with CH5424802.;

• ALK Inhibitor

  Rizotinib is a first-generation anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) and plays an important role inthe treatment of ALK-positive advanced non-small cell lung cancer (NSCLC). However, as with other TKIs, resistance development can-not be avoided with crizotinib. Alectinib is a second-generation ALK-TKI developed by Roche, which can effectively solve the problem of crizotinib resistance.

  ;

Spectrum Detail

Supplier

Related Products