ROS Kinase

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.

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.

Cucurbitacin B (Cuc B) has profound in vitro and in vivo antiproliferative effects against human pancreatic Y cells. It inhibited AKT signaling activation through up-regulation of PTEN. Cucurbitacin B is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung Y cells.

BRD5459 is a small molecule probe that elevates markers of oxidative stress without leading to cell death.

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.

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

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.

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.

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.

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.

MitoPQ (MitoParaquat) is a mitochondria-targeted small molecule compound that selectively enhances mitochondrial superoxide and hydrogen peroxide levels and inhibits insulin-stimulated glucose uptake and translocation of glucose transport protein 4 (GLUT4) to the plasma membrane in adipocytes and myotubes.MitoPQ can be used to MitoPQ can be used to study mitochondrial oxidative stress and regulated GLUT4 transporter.

Mefloquine (Ro 215998), a quinoline antimalarial agent, is an anti-SARS-CoV-2 entry inhibitor. Mefloquine is also a K+ channel (KvQT1/minK) antagonist with an IC50 of ~1 μM. Mefloquine can be used for malaria, systemic lupus erythematosus, and cancer research.

Mefloquine hydrochloride (Mefloquin hydrochloride) is a quinoline derivative used for the prevention and therapy of P. falciparum malaria.

L-Cystine (Cystine Acid) is not considered one of the 20 amino acids, L-Cystine (Cystine Acid) is a sulfur-containing derivative obtained from oxidation of cysteine amino acid thiol side chains. It functions as an antioxidant and protects tissues against radiation and pollution, slowing the aging process. It also aids protein synthesis. L-Cystine (Cystine Acid) is abundant in many proteins of skeletal tissues and skin, and found in insulin and digestive enzymes chromotrypsinogen A, papain, and trypsinogen.

Higenamine hydrochloride (norcoclaurine HCl) has been demonstrated to be a β2 adrenoreceptor agonist. Adrenergic receptors, or adrenoceptors, belong to the class of G protein–coupled receptors, and are the most prominent receptors in the adipose membrane, besides also being expressed in skeletal muscle tissue.

DMNQ is a 1,4-naphthoquinone that acts as a redox-cycling agent, typically increasing intracellular superoxide and hydrogen peroxide formation.DMNQ increases ROS generation

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

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.

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.

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.

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.

Merestinib dihydrochloride (LY2801653 dihydrochloride) is an orally available kinase inhibitor with antitumor activity that inhibits MET, AXL, RON, and MKNK1/2, and inhibits the growth of NTRK fusion-carrying tumors.

F-1 is IC50s of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM for ALKWT, ROS1WT, ALKL1196M and ALKG1202R, respectively. F-1 is a potent ALK and ROS1 dual inhibitor, suppresses phospho-ALK and its relative downstream signaling pathways.

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.