multi-target

Multi-target kinase inhibitor 3 (compound 6i) is a potent multi-target anticancer agent.

Multi-target kinase inhibitor 4 (Compound 2) is a PI3K/DNA-PK inhibitor and a potent chemosensitizer that enhances the number of DNA double-strand breaks induced by Doxorubicin. It serves as an effective multidrug resistance (MDR) inhibitor, demonstrating inhibitory activity against P-glycoprotein (P-gp) mediated drug efflux. Multi-target kinase inhibitor 4 can be encapsulated in PEG-coated lipid nanoparticles.

Multi-target Pt (IV) is an antitumor agent that inhibits the phosphorylation of IKKβ, IκBα, and NF-κB p65, as well as the nuclear translocation of NF-κB p65, ultimately blocking the NF-κB signaling pathway.

Multi-target kinase-IN-5 (Compound 23) is an orally active ERK1/2 inhibitor with IC50 values of 3.04 nM and 1.57 nM, respectively. It notably suppresses cancer cell proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest. By inhibiting the phosphorylation of ERK1/2 and downregulating the activity of its downstream substrate RSK, Multi-target kinase-IN-5 exhibits antitumor effects. This compound can be utilized in cancer research.

Compound 5K (Multi-target kinase inhibitor 2) is a multi-targeted kinase inhibitor demonstrating activity against EGFR, Her2, VEGFR2, and CDK2 with IC50 values between 40 to 204 nM. It exhibits cytotoxic effects on HepG2, HeLa, MDA-MB-231, and MCF-7 cell lines, with IC50 values of 41, 57, 51, and 59 μM, respectively. Additionally, it induces cell cycle arrest and apoptosis specifically in HepG2 cells.

Multitarget AD inhibitor-2 (Compound VN-19) is a versatile inhibitor targeting multiple sites, acting on acetylcholinesterase (AChE, IC50 = 0.14 μM), butyrylcholinesterase (BChE, IC50 = 11.6 μM), and monoamine oxidase B (MAO B, IC50 = 0.45 μM). It inhibits amyloid-beta protein Aβ1-42 self-induced aggregation with an inhibition rate of 47.3% at 20 μM and reduces ROS levels in SH-SY5Y cells with an inhibition rate of 80% at 25 μM. Multitarget AD inhibitor-2 can also improve cognitive decline in a scopolamine-induced Alzheimer's zebrafish model.

Multitarget AD inhibitor-1 is a reversible and selective inhibitor of butyrylcholinesterase (BuChE) with IC50 values of 7.22 μM for human BuChE (hBuChE) and 1.55 μM for equine serum BuChE (eqBuChE). It also exhibits inhibitory activity towards β-secretase (IC50 41.60 μM), amyloid β aggregation (IC50 3.09 μM), and tau aggregation. As a diphenylpropylamine derivative, Multitarget AD inhibitor-1 is promising for research into multifunctional, disease-modifying treatments for Alzheimer's disease.

Ponatinib (AP24534) is an orally available, multitargeted kinase inhibitor with IC50 values of 0.37 nM (Abl), 1.1 nM (PDGFRα), 1.5 nM (VEGFR2), 2.2 nM (FGFR1), and 5.4 nM (Src).

Dovitinib lactate hydrate (TKI258) is the Lactate of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGFR1 and HER2. Phase 4.

Lenvatinib (E7080) is a multi-target receptor tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, KIT, PDGFR, and RET, and has oral activity. Lenvatinib has the strongest inhibitory activity on VEGFR2 and VEGFR3 (IC50=4/5.2 nM). Lenvatinib has strong anti-tumor activity.

C-Myc Inhibitor 7, serving as both a c-Myc inhibitor and a multi-target protein degrader, effectively degrades proteins c-MYC, CK1α, GSPT1, and IKZF1/2/3 across various tumor cell types. It holds potential for research into diseases associated with high c-Myc expression, including cancer, cardiovascular and cerebrovascular conditions, and viral infections.

PARP1/2/TNKS1/2-IN-1 is a multi-target inhibitor of PARP-1, PARP-2, TNKS1, and TNKS2, with potential anti-tumor activity that induces apoptosis.

Antimicrobial agent-22 (THI 6c) is a broad-spectrum, multi-target antibacterial with rapid bactericidal efficacy, effective anti-biofilm activity, and low cytotoxicity and hemolytic properties [1].

Pazopanib Hydrochloride (Votrient HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively.

Regorafénib N-oxyde M2 is an active metabolite of Regorafenib, a multi-target inhibitor for VEGFR1/2/3, PDGFRβ, RET, Kit, and Raf-1 (IC50s: 13/4.2/46, 1.5, 22, 7, and 2.5 nM).

Imatinib-d8 (STI571 D8) is a 2H-labeled version of Imatinib. Imatinib is a multi-target receptor tyrosine kinase inhibitor with anti-tumor activity, selectively inhibiting BCR-ABL, v-Abl, PDGFR, c-kit kinases, and is used in chronic myeloid leukemia treatment.

N-Desmethyl imatinib (Imatinib metabolite N-Desmethyl imatinib) is a metabolite of Imatinib, which is a multi-target inhibitor of c-Kit, v-Abl, and PDGFR.

Compound AuL9, also known as iNOS/TopoI-IN-1, is a multi-target hybrid molecule possessing anti-tumor, anti-inflammatory, and antioxidant properties. This compound effectively inhibits the growth of MCF-7 and MDA MB-231 breast cancer cells in vitro, exhibiting IC50 values of 3.5 μM and 6.3 μM respectively. It also prompts DNA damage and apoptosis in these cells by inhibiting human topoisomerase I (TopoI) with a K_i of 2.72 μM. Additionally, iNOS/TopoI-IN-1 reduces the expression of iNOS by suppressing the activation of NF-kB, with a K_i of 1.49 μM.

TG-100435 is a novel multi-target oral protein tyrosine kinase inhibitor. The metabolic flux of TG100435 is entirely inhibited by methimazole and ketoconazole. In human liver microsomes or recombinant P450, the formation of TG100435 increases with the activity of cytochrome P450 reductase, suggesting that cytochrome P450 reductase may be involved.

hAChE/hBuChE/GSK-3β-IN-1 (Compound 6c) is a multi-target compound designed for Alzheimer's treatment capable of crossing the blood-brain barrier. It inhibits hAChE with an IC50 of 28.88 nM, hBuChE with an IC50 of 131.90 nM, and GSK-3β with an IC50 of 51.42 nM. Additionally, it acts as an inhibitor of tau protein and Aβ protein aggregation.

Apoptosisinducer 35 (Compound 6) is a multi-target inhibitor that reduces the expression of EGFR, AKT, ERK, and P38-MAPKα. It suppresses the proliferation of cancer cells A549 and Jurkat, induces cell cycle arrest at the S phase, and triggers apoptosis (cell death).

RA-PR058 is an orally active Ramalin derivative capable of penetrating the blood-brain barrier, with multi-target regulatory functions. By reducing BACE1 expression, decreasing excessive tau protein phosphorylation, and mitigating anxiety-like behaviors, along with displaying favorable pharmacokinetic properties, RA-PR058 shows promise as a multi-target modulator for Alzheimer's disease.

AChE/BChE/MAO-B-IN-5 is a multi-target inhibitor capable of crossing the blood-brain barrier, targeting cholinesterases (AChE and BChE) and monoamine oxidase MAO-B. It exhibits IC50 values of 0.24 µM for AChE, 6.29 µM for BChE, and 0.11 µM for MAO-B. AChE/BChE/MAO-B-IN-5 holds potential for research in neurodegenerative diseases such as Alzheimer's disease.

GSK3-IN-10 (Compound 4) is a multi-target inhibitor primarily affecting GSK3α and GSK3β with IC50 values of 1.0 nM and 2.0 nM, respectively. It inhibits the activation of β-catenin, enhances neuronal survival, and provides protective effects against endoplasmic reticulum stress.