VEGFR Inhibitor

YLT192 is an orally active and highly bioavailable VEGFR2 inhibitor with potent anti-angiogenic activity and anti-tumor efficacy. YLT192 significantly inhibited the kinase activity of VEGFR2 and inhibited the proliferation, migration, invasion and tube formation of human umbilical cord vascular endothelial cells. YLT192 also inhibited VEGF-induced VEGFR2 phosphorylation and its downstream signaling regulators. YLT192 also showed the ability to inhibit angiogenesis in vivo in zebrafish embryo models and alginate-coated tumor cell experiments. YLT192 can directly inhibit the proliferation of cancer cells and induce their apoptosis.

EG00229 is an inhibitor for VEGF-A and NRP1 interaction with an IC₅₀ of 8 μM. EG00229 inhibits the migration of HUVECS and the phosphorylation of VEGFR2 in endothelial cells. EG00229 exhibits cytotoxicity in cancer cell A549.

MSB-0254 is a human monoclonal antibody (mAb) targeting VEGFR2/KDR/CD309. MSB-0254 inhibits the invasion, migration, and vascular mimetic (VM) formation of U251 and primary glioma cells. MSB-0254 inhibits the growth of U251 and GL261 cell transplanted tumors. MSB-0254 reduces the expression of CD34, VEGFR2, Ki67, MMP2, MMP9, and CD34/PAS. MSB-0254 can be used in advanced solid tumors research.

VEGFR-2-IN-57 (compound 6n) exhibited significant cytotoxicity in HUVEC cells (IC50 = 28.77 nM).

MW02 is a human monoclonal antibody (mAb) targeting VEGFA. MW02 can be used in Wet age-related macular degeneration research.

CS2009 is a trispecific antibody targeting PD-1, CTLA-4 and VEGFA. CS2009 blocks the interactions of PD-1/PD-L1, CTLA-4/CD80 and VEGFA/VEGFR2, mediates checkpoint inhibition, and suppresses tumor angiogenesis. CS2009 reactivates PD-1/CTLA-4 double-positive tumor-infiltrating T lymphocytes, induces T cell activation, enhances tumor growth inhibition, promotes vascular normalization, improves T lymphocyte infiltration, and converts the immunosuppressive tumor microenvironment into an immunocompetent one. CS2009 can be used for the research of various advanced solid tumors.

VEGF-IN-1 (compound 6) can reduce the release of VEGF in U87-MG cells and inhibit angiogenesis in vitro. VEGF-IN-1 can inhibit cell proliferation by inducing autophagy in tumor cells, with an IC₅₀ value of 28.35 μM for U87-MG cells.

CEP-7055 (compound 21) is a novel vascular endothelial growth factor R2 (VEGF-R2) tyrosine kinase inhibitor with potent inhibitory activity. Studies have found that the inhibitor activity can be significantly improved by optimizing the R9 substituent. Compound 21 has potent low nanomolar inhibition of human VEGF-R tyrosine kinase and shows good selectivity against multiple tyrosine and serine/threonine kinases. N,N-dimethylglycine ester 40 was prepared to improve its water solubility and oral bioavailability. In animal pharmacokinetic studies, a significant increase in the plasma level of 21 was observed after oral administration of 40. Compound 21 showed significant in vivo antitumor activity in multiple tumor models and has entered phase I clinical trials as a water-soluble N,N-dimethylglycine ester proagent of 40 (CEP-7055).

CPD-002 is an inhibitor for vascular endothelial growth factor receptor 2 (VEGFR 2), that inhibits angiogenesis through inhibition of VEGFR2/PI3K/AKT signaling pathway. CPD-002 exhibits anti-inflammatory activity and attenuates rheumatoid arthritis.

GW701427A is a dual inhibitor of Fluc and VEGFR2 with IC₅₀ of 0.12 μM and 603 nM, respectively. GW701427A acts as a protein kinase inhibitor across ATP-dependent and -independent luciferases with potential implications for Fluc reporter assays.

PD-1/PD-L1-IN-69 is an orally active PD-L1 dimerization inducer and FAK phosphorylation inhibitor (IC₅₀ = 18.7 nM for human PD-1/PD-L1 interaction). PD-1/PD-L1-IN-69 blocks the PD-1/PD-L1 interaction by stabilizing dimerization within the PD-L1 dimerization pocket, and inhibits VEGF-A-induced FAK phosphorylation and angiogenesis, thereby enhancing immune-mediated tumor cell death. PD-1/PD-L1-IN-69 can be used for research on colon adenocarcinoma.

CEP-5214, derived from a new indenopyrrolocarbazole template, is a potent inhibitor of vascular endothelial growth factor R2 (VEGF-R2) tyrosine kinase. Structurally, it features optimal substitutions at positions 9 (ethoxymethyl) and 12 (hydroxypropyl) on the indeno[2,1-a]pyrrolo[3,4-c]carbazole-5-one scaffold, leading to high potency against VEGF-R2 (IC₅₀ 8 nM). Compound 21 (CEP-5214) exhibits low-nanomolar inhibition of human VEGF-R tyrosine kinases (IC₅₀ 4 nM for VEGF-R2/KDR), with good selectivity over other kinases. The compound demonstrated significant cellular and in vivo antitumor activity across various models and advanced into phase I clinical trials as a water-soluble prodrug (CEP-7055) to enhance oral bioavailability.

AGN-745 sodium is a chemically modified siRNA targeted to VEGFR-1. It is used for the study of Macular degeneration.

VEGFR-2-IN-20 (Compound 7) is a potent inhibitor of VEGFR. VEGFR-2-IN-20 has the potential for the research of cancer diseases.

Antiproliferative agent-54 (Compound 6z) is the inhibitor for multiple kinases, such as ABL WT, B-RAF, EGFR, HCK, LYN A and SRC with IC₅₀ of 6-50 nM. Antiproliferative agent-54 inhibits proliferation of several cancer cell, inhibits HUVEC and HepG2, with EC₅₀ of 34 and 38 nM. Antiproliferative agent-54 exhibits good pharmacokinetic characteristics in rats.

VEGFR-2-IN-56 (compund 12e) is a potent VEGFR-2 inhibitor (IC₅₀=45.9 nM).

VEGFR-2-IN-52 (compound 14d) is a potent VEGFR-2 inhibitor with an IC₅₀ value of 191.1 nM. VEGFR-2-IN-52 decreases the protein expression of p-VEGFR-2, MMP9, p-ERK1/2 and p-MEK1. VEGFR-2-IN-52 shows cytotoxicity. VEGFR-2-IN-52 induces apoptosis and cell cycle arrest at G0/G1 phase. VEGFR-2-IN-52 increases the levels of ROS.

Jolkinolide A is a diterpenoid, can be extracted from the roots of Euphorbia fischeriana Steud. Jolkinolide A exhibits anti-tumor activity, by affecting on angiogenesis of tumor tissues. Jolkinolide A significantly inhibits the Akt-STAT3-mTOR signaling pathway and reduces the expression of VEGF in A549 cells.

VEGFR/PARP-IN-1 (Compound 14b) is a VEGFR/PARP dual inhibitor (IC₅₀s: 191 nM and 60.9 nM respectively). VEGFR/PARP-IN-1 inhibits DNA damage repair, induces cell apoptosis, and arrests cell in the G2/M phase. VEGFR/PARP-IN-1 has good antiproliferative efficacy against BRCA wild-type breast cancer cells (IC₅₀: 4.1 and 3.5 μM for MDA-MB-231 and MCF-7 cells). VEGFR/PARP-IN-1 is an antitumor and anti-metastasis agent.

VEGFR-2-IN-63 (Compound 12b) is the inhibitor for VEGFR2 that inhibits 87.2% VEGFR-2 at 10 μM. VEGFR-2-IN-63 exhibits antiproliferative activity in multiple cancer cell, IC₅₀s for HCT116, MCF7 and PaCa2 is 6.5 μM, 2.1 μM and 4.1 μM, respectively.