Angiogenesis

ZM323881 hydrochloride is a potent and selective VEGFR2 inhibitor with an IC50 of less than 2 nM.

Norcantharidin (Endothall anhydride) is a synthetic anticancer compound which is a dual inhibitor for c-Met and EGFR in human colon cancers.

2,5-Dihydroxybenzoic acid is a derivative of benzoic and a powerful inhibitor of fibroblast growth factors.

BTK inhibitor 1 (compound 27) is an inhibitor of BTK with an IC50 of 0.11 nM for Btk and inhibits B cell activation in hWB with an IC50 of 2 nM.

XL092 is an ATP-competitive inhibitor of multiple RTKs including MET, VEGFR2, AXL and MER, with IC50 values in cell-based assays of 15, 1.6, 3.4, and 7.2 nM respectively.

Emavusertib, also known as CA-4948 is a potent IRAK4/FLT3 inhibitor with anti-tumor activity. CA-4948 demonstrated good cellular activity in ABC DLBCL and AML cell lines. CA-4948 demonstrated moderate to high selectivity in a panel of 329 kinases as well as exhibited desirable ADME and PK profiles including good oral bioavailability in mice, rat, and dog and showed >90% tumor growth inhibition in relevant tumor models with excellent correlation with in vivo PD modulation.

Vodobatinib, also known as K-0706, is a novel 3rd generation (3G) TKI effective against wild-type and mutated BCR-ABL1 with limited off-target activity.

SU4984 is a cell-permeable, reversible, and ATP-competitive inhibitor of the tyrosine kinase activity of fibroblast growth factor receptor 1 (FGFR1; IC50 = 10-20 μM).

Seralutinibm, also known as PK-10571 and GB002, is a Inhaled Pdgfr Kinase Inhibitor.

E-7090 is a fibroblast growth factor receptor inhibitor potentially for the treatment of solid tumors.

JNJ 10198409 is a potent platelet-derived growth factor receptor (PDGFR) inhibitor (IC50 values are 4.2 and 45 nM for PDGFRβ and PDGFRα, respectively). Also inhibits c-Abl, Lck, c-Src and Fyn kinases (IC50 values are 22, 100, 185 and 378 nM respectively).

Multi-kinase inhibitor 1 is a potent multi-kinase inhibitor. Multi-kinase inhibitor 1 has the potential for diseases or disorders associated with abnormal or deregulated tyrosine kinase activity, particularly diseases associated with the activity of PDGF-R, c-Kit and Bcr-abl.

SU-4312, also known as DMBI, is a potent and selective inhibitor of VEGFR and PDGFR tyrosine kinases (IC50 values are 0.8 and 19.4 μM respectively).

SU-4313 is a small-molecule modulator of protein tyrosine kinases (PTKs). It inhibits multiple receptor tyrosine kinases with reported IC₅₀ values of 14.5 μM (PDGFR), 18.8 μM (FLK-1/VEGFR2), 11 μM (EGFR), 16.9 μM (HER2 kinase), and 8.0 μM (IGF-1R).

Through its multi-kinase inhibitory profile, SU-4313 modulates tyrosine kinase–mediated signal transduction pathways involved in the regulation of cell proliferation and growth. It is therefore commonly used as a research tool for investigating aberrant receptor tyrosine kinase signaling and proliferation-associated pathways.

5'-Fluoroindirubinoxime (5'-FIO, compound 13), an Indirubin derivative, is a potent FLT3 inhibitor, with an IC50 of 15 nM.

Gramicidin A is a peptide component of gramicidin, an antibiotic mixture originally isolated from B. brevis. Gramicidin A is a highly hydrophobic channel-forming ionophore that forms channels in model membranes that are permeable to monovalent cations. Gramicidin A induces degradation of hypoxia inducible factor 1 α (HIF-1α).

VSPPLTLGQLLS is a small peptide FGFR3 inhibitor, peptide P3, inhibits FGFR3 phosphorylation. VSPPLTLGQLLS inhibits 9-cisRA-induced tracheal lymphangiogenesis and blocks lymphatic endothelial cell (LEC) proliferation, migration, and tubule formation.

PRLX-93936 dihydrochloride (Compound 16) is a small-molecule inhibitor of hypoxia-inducible factor 1α (HIF-1α) with demonstrated anticancer activity. It also suppresses signaling within the activated Ras pathway, thereby inhibiting tumor cell proliferation and survival. PRLX-93936 shows potential therapeutic relevance in the study of relapsed or refractory multiple myeloma and other Ras-driven malignancies, making it a useful compound for investigating hypoxia-related and oncogenic signaling mechanisms in cancer.

GBD-9 is a dual-action degrader that targets both BTK and GSPT1 by recruiting the E3 ligase cereblon (CRBN). It acts as a PROTAC to promote BTK degradation and functions as a molecular glue to induce GSPT1 degradation. GBD-9 exhibits significant antiproliferative activity in cancer cells, making it a promising candidate for cancer research.

LC-MB12 is an orally active PROTAC compound that targets FGFR2 degradation, with a DC₅₀ of 11.8 nM. It consists of the FGFR2 inhibitor BGJ398, a PROTAC linker, and a cereblon (CRBN) ligand. LC-MB12 effectively inhibits FGFR2 signaling in gastric cancer cells and exhibits antitumor activity.

ATWLPPR peptide is a biologically active heptapeptide and a specific antagonist of VEGFR2 (KDR/Flk-1). It binds to VEGFR2, completely blocking VEGF binding and thereby inhibiting VEGF-induced angiogenesis in vivo. ATWLPPR selectively inhibits human endothelial cell proliferation in vitro and fully suppresses VEGF-mediated angiogenesis in vivo.

DB0614 is a PROTAC molecule utilizing a cereblon ligand, designed as a selective and potent degrader of NEK9 and other kinases. It induces the degradation of multiple kinases, including ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1–3, MAP4K5, MAPK14, MAPK7–9, MAPKAPK2/3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1/3, SIK2/3, STK35, TNK2, and ULK1. DB0614 is suitable for research involving diseases or disorders driven by aberrant kinase activity.

Bleximenib (JNJ-75276617) is an orally active and highly selective menin–KMT2A (MLL) interaction inhibitor, with IC50 values of 0.1 nM in humans, 0.045 nM in mice, and ≤0.066 nM in dogs. It effectively inhibits the proliferation of tumor cells and induces apoptosis and differentiation, particularly in malignancies driven by KMT2A rearrangements. Bleximenib is a promising therapeutic candidate for the study and treatment of leukemia and other menin-dependent cancers.

Zongertinib (BI 1810631) is a potent and selective tyrosine kinase inhibitor targeting HER2 and EGFR, with IC50 values of 13 nM and 579 nM, respectively. It exhibits significant antitumor activity and is being investigated for the treatment of multiple solid tumors, particularly those driven by HER2 alterations.

Bleximenib (JNJ-75276617) oxalate is an orally active and highly selective inhibitor of the menin–KMT2A (MLL) interaction, with IC50 values of 0.1 nM in humans, 0.045 nM in mice, and ≤0.066 nM in dogs. It effectively inhibits tumor cell proliferation and induces apoptosis and differentiation, particularly in cancers driven by KMT2A rearrangements. Bleximenib oxalate is a promising candidate for research in leukemia and other menin–KMT2A-dependent malignancies.

6-Demethoxytangeretin is a flavonoid compound isolated from *Citrus reticulata* with demonstrated anti-inflammatory and anti-allergic properties. It inhibits IL-6 production and the expression of related genes in human mast cells by modulating the ALK and MAPK signaling pathways. Additionally, 6-Demethoxytangeretin enhances CRE-mediated transcription in hippocampal neurons, indicating potential neuroregulatory effects.

Flonoltinib is a potent and orally active dual JAK2/FLT3 inhibitor with IC50 values of 0.7 nM for JAK2, 4 nM for FLT3, 26 nM for JAK1, and 39 nM for JAK3. It exhibits strong anti-cancer activity and is a promising candidate for the treatment of hematologic malignancies and other JAK/FLT3-driven cancers.

Iruplinalkib (WX-0593) is an orally active and selective ALK/ROS1 inhibitor that effectively blocks tyrosine autophosphorylation of ALK, mutant ALK, and EGFR, with IC50 values ranging from 5.38 to 16.74 nM. Additionally, it inhibits the transport activity of MATE1, MATE2K, P-gp, and BCRP. Iruplinalkib is under investigation for the treatment of non-small cell lung cancer (NSCLC).

Methylnissolin (Astrapterocarpan), a natural compound isolated from *Astragalus membranaceus*, inhibits PDGF-BB-induced vascular smooth muscle cell proliferation with an IC50 of 10 μM. It exerts its effects by suppressing PDGF-BB-induced phosphorylation of ERK1/2, thereby blocking activation of the ERK1/2 MAP kinase signaling cascade.

JG26 is a potent ADAM inhibitor with IC50 values of 12 nM for ADAM8, 1.9 nM for ADAM17, and 150 nM for ADAM10. It also inhibits MMP-12 with an IC50 of 9.4 nM. JG26 suppresses AngII-induced EGFR transactivation and ERK activation, upregulates ACE2 expression, inhibits CD23 shedding, and reduces SARS-CoV-2 infection. Additionally, JG26 demonstrates anti-metastatic effects in colorectal cancer and holds research potential in Hodgkin lymphoma and vascular diseases.

Lasmotinib (PHI-101) is a dual inhibitor of FLT3 and CHK2 with potent activity against FLT3 single activating mutations (ITD or TKD), as well as double (ITD/D835Y or ITD/F691L) and triple (ITD/D835Y/F691L) resistance mutations. It synergizes with Venetoclax or Azacytidine to enhance anti-leukemic effects and also demonstrates anticancer activity in ovarian and breast cancer models.

Ifebemtinib (BI-853520, IN-10018) is an orally active and potent inhibitor of focal adhesion kinase (FAK), with an IC50 of 1 nM against recombinant FAK. It exhibits antiproliferative activity in cancer cells and also inhibits FER and FES kinases, with IC50 values of 900 nM and 1040 nM, respectively.

Sulforaphene, a natural compound isolated from radish seeds, exhibits an ED₅₀ of approximately 2 × 10⁻⁴ M against velvetleaf seedlings. It promotes apoptosis and inhibits migration in cancer cells by suppressing signaling pathways including EGFR, phosphorylated ERK1/2 (p-ERK1/2), and NF-κB.

Avitinib (Abivertinib) maleate is a third-generation, irreversible, and orally active selective EGFR inhibitor with IC50 values of 0.18 nM for both EGFR^L858R and EGFR^T790M, and 7.68 nM for wild-type EGFR. In addition to its EGFR-targeting activity, Avitinib maleate also inhibits BTK phosphorylation and induces apoptosis in mantle cell lymphoma models, demonstrating broad-spectrum anticancer efficacy.

JND3229 is a reversible EGFR C797S inhibitor with IC50 values of 5.8 nM for EGFR^L858R/T790M/C797S, 6.8 nM for EGFR^WT, and 30.5 nM for EGFR^L858R/T790M. It exhibits potent antiproliferative activity and effectively suppresses tumor growth in vivo, making it a valuable tool for cancer research, particularly in the context of non-small cell lung carcinoma.

Silevertinib (BDTX-1535, EGFR-IN-76) is an orally bioavailable, blood-brain barrier-permeable, and selective EGFR inhibitor with demonstrated antitumor activity. It has shown efficacy in preclinical models of non-small cell lung cancer (NSCLC), glioblastoma patient-derived tumors, and intracranial tumor models.

Befotertinib (D-0316) mesylate is an orally active EGFR tyrosine kinase inhibitor that suppresses tumor cell proliferation. It is primarily investigated for its potential in treating EGFR T790M-positive non-small cell lung cancer (NSCLC).

O-Desmethyl gefitinib is an active plasma metabolite of gefitinib, formed via CYP2D6-mediated metabolism. It retains EGFR inhibitory activity with an IC50 of 36 nM in subcellular assays.

MTX-531 is an orally active small molecule that inhibits EGFR (IC50 = 14.7 nM) and multiple PI3K isoforms, with IC50 values of 6.4 nM (PI3Kα), 233 nM (PI3Kβ), 8.3 nM (PI3Kγ), and 1.1 nM (PI3Kδ), demonstrating potent antitumor activity. Additionally, MTX-531 functions as a weak PPARγ agonist (IC50 = 2.5 µM), which may mitigate PI3K inhibitor-induced hyperglycemia.

Rezivertinib (BPI-7711) is an orally active, highly selective, and irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It is designed to potently target both common activating EGFR mutations and the resistance-associated T790M mutation, which is a frequent cause of acquired resistance to earlier-generation TKIs. Rezivertinib also demonstrates excellent central nervous system (CNS) penetration, making it effective against brain metastases in EGFR-mutant non-small cell lung cancer (NSCLC). With its strong antitumor activity and favorable pharmacokinetic profile, Rezivertinib is a promising candidate for the treatment of EGFR-mutant NSCLC, particularly in patients with CNS involvement or T790M-driven resistance.

Dacomitinib (PF-00299804) hydrate is an orally active, irreversible pan-ErbB inhibitor targeting EGFR, HER2, and HER4. It potently inhibits ErbB family signaling pathways, suppressing tumor proliferation and survival. Dacomitinib hydrate is a valuable agent for research into cancers, particularly metastatic non-small cell lung cancer (NSCLC), where it demonstrates efficacy in targeting EGFR-driven oncogenesis.

PP 3 (Compound 3) is an EGFR tyrosine kinase inhibitor with an IC50 of 2.7 μM. It targets the EGFR signaling pathway, which is critical for cell proliferation and survival in various cancers. PP 3 is a useful tool for research into EGFR-driven malignancies, such as non-small cell lung cancer and head and neck squamous cell carcinoma, enabling studies on tumor growth inhibition and potential therapeutic strategies.

Tyrphostin AG1433 (SU1433) is a tyrosine kinase inhibitor that selectively targets platelet-derived growth factor receptor beta (PDGFRβ) and vascular endothelial growth factor receptor 2 (VEGFR-2/Flk-1/KDR), with IC₅₀ values of 5.0 μM and 9.3 μM, respectively. By inhibiting these key angiogenic receptors, AG1433 disrupts downstream signaling involved in endothelial cell proliferation and migration, thereby effectively preventing blood vessel formation (angiogenesis). It is a valuable compound for research into tumor angiogenesis, vascular disorders, and anti-angiogenic therapeutic strategies.

VEGFR2-IN-2 (compound 6e) is a highly potent and selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), exhibiting an IC50 of 19.32 nM. It effectively targets VEGFR2-mediated signaling, which is critical for tumor angiogenesis, thereby inhibiting tumor growth and metastasis. VEGFR2-IN-2 is a valuable tool for research into anti-angiogenic therapies, particularly for cancers such as colorectal, breast, lung, and ovarian cancers, where VEGFR2-driven angiogenesis plays a significant role. Its high selectivity and potency make it suitable for studying VEGFR2-specific mechanisms in tumor progression and evaluating combination therapies with other targeted agents.

EVT801 is an orally active, selective VEGFR-3 inhibitor (IC50=11 nM) with potent antitumor properties. It suppresses VEGF-C-induced human endothelial cell proliferation and tumor-associated lymphatic angiogenesis in mouse models. EVT801 reduces tumor hypoxia, immunosuppressive cytokines (CCL4, CCL5), and myeloid-derived suppressor cell (MDSC) production. When combined with immune checkpoint therapy (ICT), EVT801 enhances response rates and improves tumor inhibition in cancer mouse models. Additionally, EVT801 is a click chemistry reagent containing an alkyne group, enabling copper-catalyzed azide-alkyne cycloaddition (CuAAC) with azide-containing molecules.

Tinengotinib (TT00420) is an orally bioavailable, spectrally selective small-molecule kinase inhibitor targeting Aurora A/B (IC50=1.2–3.3 nM), FGFR1/2/3 (IC50=1.5–3.5 nM), VEGFRs, JAK1/2, and CSF1R. It disrupts Aurora kinase-mediated cell cycle progression, inducing G2/M arrest, inhibits the FGFR/JNK-JUN signaling pathway, and activates the MEK/ERK-dependent apoptotic pathway. Tinengotinib exhibits potent anti-tumor proliferation, pro-apoptotic, anti-angiogenic, and tumor microenvironment-modulating activities. It is a promising candidate for research in triple-negative breast cancer (TNBC), gallbladder cancer, and tumor immune microenvironment studies.

Gunagratinib (ICP-192) is a low-toxicity, orally active, irreversible pan-FGFR inhibitor that covalently binds to fibroblast growth factor receptors (FGFR1–4), potently and selectively blocking FGFR-mediated signaling. It is designed for the treatment and study of FGFR-driven cancers, including those with FGFR alterations implicated in tumor growth and survival.

Irpagratinib (ABSK011) is an orally active and highly potent FGFR4 (fibroblast growth factor receptor 4) inhibitor with an IC₅₀ of less than 10 nM. It effectively inhibits FGFR4 autophosphorylation, thereby blocking downstream signaling pathways critical for tumor cell survival and proliferation. Pharmacokinetic studies in mice, rats, and dogs have demonstrated high systemic exposure of Irpagratinib, supporting its potential for oral dosing in clinical applications. In preclinical models, Irpagratinib has shown significant antitumor activity, particularly in subcutaneous xenograft tumor models, making it a promising candidate for the treatment of FGFR4-driven cancers such as hepatocellular carcinoma.

Resigratinib (KIN-3248) is an irreversible, orally active covalent inhibitor targeting fibroblast growth factor receptors FGFR1–4. It binds covalently to the conserved cysteine residue Cys492 within the kinase domain, effectively blocking FGFR signaling. Resigratinib demonstrates potent activity against both wild-type FGFRs and clinically relevant drug-resistant mutations, including FGFR2 V565F and FGFR3 V555M.

Lirafugratinib (RLY-4008) is an orally active, irreversible, and highly selective inhibitor of fibroblast growth factor receptor 2 (FGFR2), with an IC₅₀ of 3 nM. It covalently binds to cysteine 491 (Cys491) in the FGFR2 kinase domain, enabling durable inhibition of FGFR2 signaling. Lirafugratinib is specifically designed to target FGFR2-driven cancers, including those with primary activating alterations and acquired resistance mutations, while sparing other FGFR family members to minimize off-target effects. It has demonstrated potent antitumor activity, including tumor regression, making it a promising therapeutic candidate for FGFR2-altered malignancies such as intrahepatic cholangiocarcinoma and other solid tumors.