Anaplastic lymphoma kinase (ALK) Inhibitor

Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitive ALK and c-Met inhibitor with IC₅₀s of 20 and 8 nM, respectively. Crizotinib inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC₅₀s of 24 and 11 nM in cell-based assays, respectively. Crizotinib is also a ROS1 inhibitor. Crizotinib has effective tumor growth inhibition.

Lorlatinib (PF-06463922) is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor with anticancer activity. Lorlatinib has K_is of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALK^L1196M, respectively. Lorlatinib targets to EML4-ALK, and inhibits ALK phosphorylation with IC₅₀s of 15-43 nM (ALK^L1196), 14-80 nM (ALK^G1269A), 38-50 nM (ALK^1151Tins), 77-113 nM (ALK^G1202R), respectively.

Entrectinib (NMS-E628) is an orally active, BBB-penetrated and centrally active inhibitor of TrkA/B/C, ROS1 and ALK, with IC₅₀ values of 1, 3, 5, 12 and 7 nM, respectively. Entrectinib induces apoptosis and cycle arrest in cancer cells, has antitumor activity, and attenuates bleomycin-induced lung fibrosis in mice.

Ceritinib (LDK378) is a selective, orally bioavailable, and ATP-competitive ALK tyrosine kinase inhibitor with an IC₅₀ of 200 pM. Ceritinib also inhibits IGF-1R, InsR, and STK22D with IC₅₀ values of 8, 7, and 23 nM, respectively. Ceritinib shows great antitumor potency.

Alectinib (CH5424802; RO5424802; RG7853) is a potent, selective, and orally available ALK inhibitor with an IC₅₀ of 1.9 nM and a K_d value of 2.4 nM (in an ATP-competitive manner), and also inhibits ALK F1174L and ALK R1275Q with IC₅₀s of 1 nM and 3.5 nM, respectively. Alectinib demonstrates effective central nervous system (CNS) penetration.

MS4078 is a ALK PROTAC degrader with a DC₅₀ of 11 nM in SU-DHL-1 cells and a DC₅₀ of 59 nM in NCI-H2228 cells, and its K_d value for ALK binding is 19 nM. MS4078 induces ALK degradation via the ubiquitin-proteasome pathway by recruiting cereblon, and inhibits the phosphorylation of ALK and STAT3, thereby suppressing cancer cell proliferation. MS4078 is applicable for the research of non-small cell lung cancer and anaplastic large cell non-Hodgkin's lymphoma.

Crizotinib (PF-02341066) acetate is an orally bioavailable, ATP-competitive ALK and c-Met inhibitor with IC₅₀s of 20 and 8 nM, respectively. Crizotinib acetate inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC₅₀s of 24 and 11 nM in cell-based assays, respectively. Crizotinib acetate is also a ROS1 inhibitor. Crizotinib acetate has effective tumor growth inhibition.

Brigatinib (AP-26113) is a highly potent, selective and orally active ALK inhibitor, with an IC₅₀ of 0.6 nM. Brigatinib can be used for research of NSCLC.

Repotrectinib (TPX-0005) is a potent ROS1 (IC₅₀=0.07 nM) and TRK (IC₅₀=0.83/0.05/0.1 nM for TRKA/B/C) inhibitor. Repotrectinib potently inhibits WT ALK (IC₅₀=1.01 nM). Repotrectinib has anti-cancer activity.

Ceritinib (LDK378) dihydrochloride is a selective, orally bioavailable and ATP-competitive ALK tyrosine kinase inhibitor with an IC₅₀ of 200 pM. Ceritinib dihydrochloride also inhibits IGF-1R, InsR, and STK22D with IC₅₀ values of 8, 7, and 23 nM, respectively. Ceritinib dihydrochloride shows great antitumor potency.

DDO-2728 (compound 19) is a selective AlkB homologue 5 (ALKBH5) inhibitor with an IC₅₀ of 2.97 μM. DDO-2728 increases the abundance of N⁶ methyladenosine (m⁶A) modifications, inducing cell apoptosis and cycle arrest. DDO-2728 suppresses tumor growth in the MV4 11 xenograft model with favorable safety profile, shows the potential of targeting ALKBH5 in cancer research.

Neladalkib (NVL-655) is an oral ALK inhibitor, the IC₅₀ for Neladalkib in inhibiting ALK is 2.8 nM. Neladalkib promotes cell apoptosis and has anti-tumor activity.

Alectinib (CH5424802; RO5424802; RG7853) Hydrochloride is a potent, selective, and orally available ALK inhibitor with an IC₅₀ of 1.9 nM and a K_d value of 2.4 nM (in an ATP-competitive manner), and also inhibits ALK F1174L and ALK R1275Q with IC₅₀s of 1 nM and 3.5 nM, respectively. Alectinib demonstrates effective central nervous system (CNS) penetration.

NVP-TAE 684 (TAE 684) is a highly potent and selective ALK inhibitor, which blocks the growth of ALCL-derived and ALK-dependent cell lines with IC₅₀ values between 2 and 10 nM.

AZD-3463 (ALK/IGF1R inhibitor) is an orally active ALK/IGF1R inhibitor, with a K_i of 0.75 nM for ALK. AZD3463 induces apoptosis and autophagy in neuroblastoma cells.

Crizotinib hydrochloride (PF-02341066 hydrochloride) is an orally bioavailable, selective, and ATP-competitive dual ALK and c-Met inhibitor with IC₅₀s of 20 and 8 nM, respectively. Crizotinib hydrochloride (PF-02341066 hydrochloride) inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC₅₀s of 24 and 11 nM in cell-based assays, respectively. It is also a ROS proto-oncogene 1 (ROS1) inhibitor. Crizotinib hydrochloride (PF-02341066 hydrochloride) has effective tumor growth inhibition.

UNC5293 is a MERTK-selective and potent inhibitor (K_i=190 pM). UNC5293 inhibits MERTK (IC₅₀=0.9 nM) and is more selective over Axl, Tyro3 and Flt3. UNC5293 exhibits excellent mouse PK properties and is used for bone marrow leukemia research.

Ensartinib (X-396) is a BBB-permeable and dual ALK/MET inhibitor with IC₅₀s of <0.4 nM and 0.74 nM, respectively.

R-268712 is an orally active and selective ALK-5 inhibitor, with an IC₅₀ of 2.5 nM. R-268712 inhibits the phosphorylation of Smad3 in a dose-dependent manner with an IC₅₀ of 10.4 nM. R-268712 suppresses glomerulonephritis as well as glomerulosclerosis by inhibiting TGF-β signaling, which can be used in studies of renal fibrosis and cancer.

ALKBH5-IN-3 is a selective, cell active ALKBH5 inhibitor with an IC₅₀ of 0.021 μM. ALKBH5-IN-3 stabilizes ALKBH5 in HepG2 cells, and increases m⁶A level in intact cells. ALKBH5-IN-3 can be used as a versatile chemical probe to explore the biological function of ALKBH5. ALKBH5-IN-3 can be used for the research of Cancer.