X-396 is a potent and highly specific ALK small molecule tyrosine kinase inhibitors (TKIs). In Ambit kinome screens, cell growth inhibition studies, and surrogate kinase assays,X-396 was more potent inhibitors of ALK but less potent inhibitors of MET compared to PF-02341066. X-396 displayed potent antitumor activity in vivo with favorable pharmacokinetic and toxicity profiles.
Science. 2017 Dec 1;358(6367).
The target landscape of clinical kinase drugs
Ensartinib purchased from AbMole
|Source||Munich Industrial University (2018). Figure 36. X-396 (AbMole BioScience)|
|Method||Kinase binding of small molecule inhibitors|
|Cell Lines||BT-474 cells, Caki-1 cells, KM-12 and HEK-293 cells|
|Incubation Time||24 h|
|Results||Notably, the photosensitizing effect of small molecule inhibitors can also be used for photodynamic therapy of cancer.|
|Source||Science (2017). Figure 4. X-396 (Abmole Bioscience)|
|Method||Cell viability and proliferation assays|
|Cell Lines||A-431 and ACHN cells|
|Incubation Time||72 h|
|Results||Regardless of whether or not EGFR carried an activating mutation, the combination was always more effective in inhibiting cell viability and proliferation than any one drug alone.|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors.
Lovly CM et al. Cancer Res. 2011 Jul 15;71(14):4920-31. PMID: 21613408.
|Related ALK Products|
TPX-0005 is a potent ALK/ROS1/TRK inhibitor, with IC50 of 5.3 nM, 1.01 nM, 1.26 nM and 1.08 nM for SRC, WT ALK, ALK G1202R and ALK L1196M, respectively.
LDK378 2Hcl (Ceritinib) is potent inhibitor against ALK with IC50 of 0.2 nM, shows 40- and 35-fold selectivity against IGF-1R and InsR, respectively.
Entrectinib (RXDX-101) is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Phase 2.
Crizotinib is inhibitor of the c-Met kinase and the NPM-ALK. Crizotinib inhibited cell proliferation in ALK-positive ALCL cells (IC50s=30 nM). Crizotinib is useful in treatment of anaplastic large-cell lymphoma.
ALK-IN-1 is an analog of AP26113 which is a potent and selective ALK inhibitor. It is also an inhibitor of EGFR.
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