roskinase

Entrectinib (RXDX-101) is a Trk, ROS1, and ALK inhibitor that inhibits TrkA, TrkB, TrkC, ROS1, and ALK (IC50=1 3 5 12 7 nM) with oral activity and blood-brain-barrier penetration. Entrectinib exhibits both antitumor and CNS activity.

Crizotinib (PF-02341066) is an ATP-competitive small-molecule tyrosine kinase inhibitor of c-MET (IC50: 8 nM) and ALK (IC50: 20 nM) receptors.

Merestinib (LY2801653) is an orally available, small molecule inhibitor of the proto-oncogene c-Met (Ki: 2 nM) with potential antineoplastic activity. Merestinib electively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing the constitutively activated c-Met protein.

Ros-generating agent 1 has anticancer activity and generates ROS by covalently modifying Sec-498 residues of TrxR. ROS-generating agent 1 reduces intracellular TrxR protein levels and promotes ROs-dependent apoptosis and ferroptosis in NCI-H460 cells.

APG-2449, an orally active inhibitor of ALK, ROS1, and FAK, demonstrates antitumor efficacy in mouse models of non-small cell lung cancer (NSCLC) [1].

HS-291, a HtpG inhibitor targeting Borrelia burgdorferi (Bb), comprises BX-2819 (high affinity for Bb HtpG), a PEG linker, and Verteporfin (a photoactive toxin). Upon light activation, HS-291 generates reactive oxygen species that oxidize HtpG and selectively inactivate nearby proteins, leading to the rapid and irreversible inactivation of Bb [1].

PRDX1-IN-1 is a selective and potent PRDX1 inhibitor with potential anti-inflammatory and anticancer activity for the study of breast and esophageal cancer.

Anti-inflammatory agent 64 (compound 4b) demonstrates antioxidant and anti-inflammatory properties, effectively inhibiting IL-6 and TNF-α secretion and reducing paw edema [1] in both in vitro and in vivo studies.

Methyl 12-methyltridecanoate ((R)-betaxolol hydrochloride), a biosurfactant derived from Brevibacterium casei LS14, enhances the biocompatibility of functionalized silver nanoparticles in vivo [1].

ROS kinases-IN-1 is a ROS tyrosine kinase inhibitor with IC50 value of 1.22 μM. ROS kinases-IN-1 shows anti-tumor activity.

Crizotinib hydrochloride (PF-02341066 hydrochloride) is a novel inhibitor of anaplastic lymphoma kinase and c-Met, with IC50 values of 20 nM and 8 nM, respectively.

ROS kinases-IN-2, with an inhibition rate of 21.53% at 10 μM, is a potent ROS kinase inhibitor with potential anticancer activity and applications in studying abnormal cell growth.

Topo I II-IN-2 (Compound 3g) is an inhibitor of both Topo I and Topo II. It exhibits inhibitory activity against NCI-H446 and NCI-H1048 cells with IC50 values of 1.30 μM and 1.42 μM, respectively. Topo I II-IN-2 induces mitochondrial apoptosis, disrupts mitochondrial function, and stimulates activity generation. Additionally, it inhibits the PI3K Akt mTOR pathway, effectively preventing the proliferation, invasion, and migration of small cell lung cancer (SCLC) cells in vitro.

CM-728 is an oxazanonaphthoquinone that exhibits cytotoxic and antibacterial properties. It acts as a human peroxidase-1 inhibitor and serves as a source of oxidative stress affecting mitochondrial function.

ALK ROS1-IN-5 (compound X4) is a selective inhibitor of ALK and ROS1 kinases, with IC50 values of 0.512 μM for ALK and 0.766 μM for ROS1. It inhibits H2228 cells with an IC50 of 0.034 μM and induces apoptosis in cancer cells in a dose-dependent manner. Additionally, ALK ROS1-IN-5 effectively suppresses the expression of p-ALK and p-ERK in cancer cells.

Uniconazole is a plant growth regulator that inhibit cytochrome P450 707As (Ki=68 nM). CYP707As is a major ABA catabolic enzyme that catabolize Abscisic acid, accordingly suppress gibberellin and sterol biosynthesis.

Lorlatinib (PF-6463922) is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity.

Salvigenin is a potent hMAO-A inhibitor, has neuroprotective, antitumor and immunomodulatory effects.

Repotrectinib (TPX-0005) is a potent ALK ROS1 TRK inhibitor, with IC50 values of 1.01 nM for WT ALK, 5.3 nM for SRC, 1.08 nM for ALK L1196M, and 1.26 nM for ALK G1202R.

Taletrectinib (AB-106) is a new-generation selective inhibitor of ROS1 NTRK including ROS1,NTRK1,NTRK2 and NTRK3 with IC50 of 0.207 nM,0.622 nM,2.28 nM and 0.980 nM, respectively.

Iruplinalkib (WX-0593) is an orally active, selective and potent ALK and ROS1 tyrosine kinase inhibitor with anticancer activity for use in the study of non-small cell lung cancer.

ROS1-IN-2 (Compound 3), a ROS1 inhibitor, is utilized in cancer research.

Taletrectinib free base (AB-106 free base) is a novel potent, selective and orally active ROS1 NTRK inhibitor.Taletrectinib free base has potent inhibitory effects on recombinant ROS1, NTRK1, NTRK2, and NTRK3, with IC50s of 0.207, 0.622, 2.28 and 0.98 nM, respectively, Taletrectinib free base also inhibited ROS1 G2032R and other Crizotinib-resistant ROS1 mutations.

Zidesamtinib (NVL-520) is an orally active, selective, potent, and blood-brain-barrier-crossing inhibitor of ROS1 fusion and resistance mutations, inhibits ROS1 and ROS1 G2032R, and can be used in the study of non-small-cell lung cancer and solid tumors.