Angiogenèse

EG31 is an EGFR inhibitor that effectively suppresses the proliferation of triple-negative breast cancer (TNBC) cells by inhibiting the EGFR signaling pathway. It demonstrates a GI50 value of 498.90 nM for MDA-MB-231 cells and 740.73 nM for Hs578T cells, while also inducing apoptosis. Additionally, EG31 retains its antiproliferative activity against 5-fluorouracil (5-FU) resistant TNBC cells, with a GI50 of 519.5 nM. EG31 is applicable in research on TNBC resistance.

Neptinib (NEP010), a derivative of Afatinib, exhibits enhanced antitumor properties and improved pharmacokinetics when administered orally. It demonstrates a notable suppression of tumor expansion in mouse models of non-small cell lung cancer harboring various EGFR mutations. Furthermore, Neptinib effectively inhibits the EGFR kinase family, exhibiting IC 50 values of 0.24 nM for EGFR wt, 7.25 nM for EGFR L858R/T790M, 0.46 nM for EGFR L858R, and 1.79 nM for EGFR T790M.

BTK-IN-34 (compound 9h) functions as a selective BTK inhibitor, exhibiting antiproliferative effects in RAMOS cells by specifically targeting pBTK (Tyr223) while sparing upstream proteins such as Lyn and Syk in the BCR signaling pathway [1].

Tarloxotinib bromide (TH-4000) is an irreversible inhibitor of EGFR/HER2.

EGFR-IN-48: potent EGFR inhibitor, oral, IC50: 0.193-66.7 nM, blocks EGFR mutants & BaF3/PC-9 cell proliferation.

DualCathepsinL/JAK-IN-1 (Compound A8) serves as a dual inhibitor of Cathepsin L (CTSL) and JAK, exhibiting IC50 values of 0.68 μM for CTSL and 337.1 nM, 5.251 nM, 27.29 nM, and 172.6 nM for JAK1/2/3 and TYK2, respectively. This compound effectively prevents the activation of MAPK, NF-κB, and JAK/STAT signaling pathways, leading to significant anti-inflammatory therapeutic effects. DualCathepsinL/JAK-IN-1 is applicable in research on acute lung injury (ALI).

Protein kinase inhibitor 10 is a protein kinase inhibitor with IC50 values of 28.9 μM, 13.6 μM, and 2.41 μM for TAM receptors, FAK, and KIT, respectively. It can inhibit abnormal and excessive cell proliferation, showing potential for research in the field of cancer treatment.

Cernuumolide J (TMJ-105) functions as a JAK2/STAT3 inhibitor and exhibits potent activity against HEL leukemia cells by inhibiting their growth in both time-dependent and concentration-dependent manners, with an IC 50 value of 1.79 μM. This compound effectively induces G2/M phase arrest and apoptosis by downregulating the phosphorylation of JAK2, STAT3, and Erk, while simultaneously upregulating the phosphorylation of JNK and p38 MAPK. Cernuumolide J holds potential for research applications in anti-cancer therapy.

Tyk2-IN-10 acts as an inhibitor of the Tyrosine Kinase 2 (Tyk2)-mediated signaling pathway, which plays a role in inflammation regulation.

BPI-15086 is an orally active, effective, irreversible inhibitor selective for mutations, targeting both EGFR and the T790M resistance mutation tyrosine kinase. It can be utilized in the study of non-small cell lung cancer.

VEGFR-2-IN-52 (compound 14d) serves as a powerful inhibitor of VEGFR-2, exhibiting an IC 50 of 191.1 nM. It effectively reduces the protein expression levels of p-VEGFR-2, MMP9, p-ERK1/2, and p-MEK1. In addition, VEGFR-2-IN-52 demonstrates cytotoxic properties by inducing apoptosis and arresting the cell cycle at the G0/G1 phase, and it enhances the levels of ROS.

HER2-IN-21 (compound 657994) is an inhibitor of the human epidermal growth factor receptor 2 (HER2) with an IC50 value of 3.85 μM.

JP-153 is an inhibitor of Src-FAK-Paxillin signaling. It suppresses Src-dependent phosphorylation of paxillin (Y118) and subsequent activation of Akt (S473). JP-153 reduces VEGF-induced migration and proliferation of retinal endothelial cells and is applicable in the study of neovascular eye diseases.

CEP-11981 is an orally active TIE2/pan-VEGFR inhibitor with broad tyrosine kinase inhibitory activity, antitumour and anti-angiogenic, refractory solid tumours.

NDI-034858 (TAK-279) is a tyrosine kinase 2 (TYK2) inhibitor (Kd<200 pM) that targets the JH2 structural domain of Tyk2 for the treatment of autoimmune diseases

Vatalanib hydrochloride (PTK787 hydrochloride) is an orally available and highly potent tyrosine kinase (VEGF) inhibitor that reduces the number and size of Aβ plaques in the cortex of 5xFAD mice, which may be useful in the study of Alzheimer's disease and cancer.

JDTic, a 4-phenylpiperidine derivative distantly related to analgesics like meperidine and ketobemidone and more closely to the mu opioid antagonist alvimopan, exhibits a notably long duration of action, maintaining effects in animals for weeks following a single dose. This duration is not due to irreversible binding to the kappa opioid receptor but rather to altered activity of c-Jun N-terminal kinases. As a highly selective antagonist for the κ-opioid receptor, without influencing the μ- or δ-opioid receptors, JDTic has shown potential in animal studies for producing antidepressant and anxiolytic effects. It also demonstrates promise in treating addiction to substances such as cocaine and morphine, distinguishing itself structurally from other kappa antagonists like norbinaltorphimine.

XMD-17-51 Trifluoroacetate is a pyrimido-diazepinone compound that regulates protein kinases.

JAK2-IN-7 selectively inhibits JAK2 (IC50: 3 nM), shows 14-fold selectivity over JAK1/3, FLT3, induces G0/G1 arrest, apoptosis, and has antitumor effects.