Angiogenesis

Siphonaxanthin is a carotenoid found in green algae, known for targeting the death receptor 5 (DR5) on cancer cells to induce apoptosis. In human leukemia HL-60 cells, it increases DR5 expression, reduces Bcl-2 levels, and activates caspase-3. It also inhibits fibroblast growth factor receptor-1 (FGFR-1) signaling in endothelial cells. Siphonaxanthin suppresses the proliferation, migration, and tubular formation of human umbilical vein endothelial cells (HUVECs), as well as the growth of microvessels in rat aorta rings. Additionally, it has anti-inflammatory properties by blocking the translocation of high-affinity IgE receptors (FcεRI) to lipid rafts in mast cells. Siphonaxanthin shows potential for research into diseases such as cancer, diabetic retinopathy, and rheumatoid arthritis.

DHFR-IN-4 is a potent dihydrofolate reductase (DHFR) inhibitor with anti-tumour activity, inhibits EGFR and HER2 and can be used to study pancreatic cancer.

<p>DDO-02267 is a selective lysine-targeted covalent inhibitor of ALKBH5, with an IC50 value of 0.49 μM. It increases levels of N6-methyladenosine (m6A) and targets the ALKBH5-AXL signaling axis. DDO-02267 serves as a probe for studying the biological function of mRNA demethylases.</p>

FLT3/TrKA-IN-1: Potent dual kinase inhibitor for FLT3 & TrKA, promising for AML research.

JAK3/BTK-IN-3: strong dual JAK3/BTK suppressor, promising for autoimmune disease research.

JNJ-47117096 is a potent and selective MELK inhibitor with an IC50 of 23 nM, and it also exhibits strong activity against Flt3 with an IC50 of 18 nM.

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.

HI042 is an FMS-like tyrosine kinase 3 (FLT3) inhibitor, showing an IC50 value of 0.62 μM for MOLM-13 cells, 0.33 μM for MV4-11 cells, and 0.89 μM for OCI-AML3 cells. It selectively reduces the survival rate of FLT3-internal tandem duplication (FLT3-ITD) positive cell lines, induces apoptosis, disrupts cell cycle progression, and diminishes colony-forming ability. HI042 is applicable for acute myeloid leukemia (AML) research.

EGFR-IN-45: Strong EGFR/CDK2 inhibitor (IC50s: 0.4 & 1.6 μM), halts cancer cell cycle pre-G1, prompts apoptosis, also targets Topo I/II.

Antiangiogenic agent 3 blocks HUVEC cell migration, chemotaxis, and lowers Src, cdc42, MAPK gene expression.

Protein kinase inhibitor 11 (Compound I-96) is an agent that inhibits the activity of PIM-1, CDK-2, GSK-3, and SRC. It shows potential for research in cancer, autoimmune diseases, and neurodegenerative disorders.

VEGFR-2-IN-12 (compound 6g), a 2-oxoquinoxalinyl-1,2,4-triazole, is a potent inhibitor of VEGFR-2 (IC50: 0.037 μM). VEGFR-2-IN-12 has anti-tumour effects.

Potent EGFR/HER2/DHFR inhibitor for MCF-7 breast cancer; IC50: 0.153/0.108/0.291 μM; arrests G1/S phase, triggers apoptosis.

EGFR-IN-132 (Compound 23) is an EGFR inhibitor effective against various EGFR mutations including the wild-type, L858R/T790M, d19/T790M, L858R/T790M/C797S, and d19/T790M/C797S with IC50 values of 1.6, 0.025, 0.019, 0.022, and 0.029 nM, respectively. This compound demonstrates favorable pharmacokinetics with high oral bioavailability.

W23-1006 is a selective covalent ALKBH5 inhibitor. It binds to the ALKBH5 C200 residue with an IC50 value of 3.848 μM. The inhibitory activity of W23-1006 is approximately 30 times stronger than that of FTO and 8 times greater than that of ALKBH3. W23-1006 is applicable for research in triple-negative breast cancer (TNBC).

NS-062 is an orally effective, irreversible covalent inhibitor targeting EGFR, demonstrating antiproliferative activity in the resistant double mutant H1975 cells with an IC50 of 0.19 μM. It also exhibits antitumor activity in a murine H1975 xenograft model.

Ersentilide, a benzamide derivative, functions as both a β1-adrenergic receptor antagonist and an Ikr blocker. It has demonstrated efficacy in animal models of cardiac arrhythmias.

SJ11646 is a Dasatinib-based LCK PROTAC degrader with a DC50 of 0.00838 pM. It exhibits potent cytotoxicity against LCK-activated T-cell acute lymphoblastic leukemia (T-ALL) cells and primary leukemia samples, significantly prolongs LCK signal inhibition, and induces apoptosis in T-ALL cells. SJ11646 binds with high affinity to 51 human kinases, particularly ABL1, KIT, and DDR1. In mouse models of T-ALL, SJ11646 demonstrates exceptional anti-leukemic efficacy.

EGFR-IN-35, an acrylamide-based EGFR inhibitor, shows promise for EGFR mutation-related cancers like NSCLC.

FGFR-IN-16 (compound 7N) is a potent inhibitor of FGFR1, FGFR2, and FGFR4, exhibiting IC50 values of 8 nM, 4 nM, and 3.8 nM respectively. It plays a crucial role in cancer research.

<p>TYK2ligand 2 is the TYK2 ligand of PROTACTYD-68. TYD-68 is a highly potent and selective CRBN-recruiting TYK2 PROTAC degrader with a DC50 value of 0.42 nM.</p>

EGFR-IN-134 (compound 3f) is a triazolo[3,4-a]quinoline derivative and functions as a potent EGFR inhibitor with an IC50 of 0.023 µM. It induces apoptosis and necrosis in cells, and causes cell cycle arrest in the G2/M and pre-G1 phases. EGFR-IN-134 modulates the expression of apoptosis-regulating proteins by downregulating anti-apoptotic protein Bcl2 and upregulating pro-apoptotic proteins p53, Bax, and caspases 3, 8, and 9, demonstrating significant antiproliferative and anticancer activities.

SORT1-IN-5 (compound 3) is a SORT1 inhibitor capable of crossing the blood-brain barrier. The MSOH salt form of SORT1-IN-5 exhibits a certain degree of oral bioavailability.

JAK1-IN-16 (compound 4l) acts as an inhibitor of JAK1/STAT3 and effectively downregulates the expression of TLR4 protein.

FGFR1inhibitor-15 (Compound 23) is an FGFR1 inhibitor with an IC50 value of 27 μM, useful for tumor research.

ES-072, a selective inhibitor targeting the EGFR mutant (EGFR-T790M), is administered orally. By hindering EGFR-T790M activity, it activates GSK3α, which subsequently leads to the phosphorylation of PD-L1 at Ser279 and Ser283. This phosphorylation facilitates the recruitment of the E3 ubiquitin ligase ARIH1, resulting in the ubiquitination and proteasomal degradation of PD-L1. Such a process not only curtails the growth of cancer cells but also amplifies the anti-tumor immune response by diminishing PD-L1 levels. ES-072 has shown efficacy in impeding the proliferation of non-small cell lung cancer (NSCLC) cells.

RGB-286638 inhibits multiple CDKs and GSK-3β, TAK1, Jak2, MEK1 with IC50s as low as 1-54 nM.

FGFR4-IN-10 (compound 5a) is a potent, selective FGFR4 inhibitor with IC50 of 70.7 nM, sparing FGFR1-3.

WDR5-MYC-IN-2 is an inhibitor of the WDR5-MYC protein-protein interaction (PPI) with an IC50 of 0.59 μM. It is utilized in research on MYC-driven cancers and in the development of other potent WDR5-MYC PPI inhibitors.

BMS-066 is an IKKβ/Tyk2 pseudokinase inhibitor. With IC50s of 9 nM and 72 nM, respectively.

FGFR-IN-5 is a potent inhibitor of FGFR. FGFR-IN-5 has potential for research in cancer diseases.

MM-589 TFA is a potent WD repeat domain 5 (WDR5)inhibitor and mixed lineage leukemia (MLL) protein-protein interaction.

EGFR-IN-161 (Compound DD-8) is a potent and reversible inhibitor of the L858R/T790M/C797S mutant EGFR kinase, with an IC50 value of 0.87 nM. EGFR-IN-161 effectively inhibits tumor cell apoptosis, G1 phase arrest, and migration.

<p>Clifutinib (Compound 9e) is an orally active, selective inhibitor of FMS-like tyrosine kinase 3 (FLT3-ITD) with an IC50 of 15.1 nM. It inhibits FLT3-ITD kinase activity and blocks downstream signaling pathways, including RAS/MAPK, PI3K/AKT, and JAK/STAT5. Clifutinib induces apoptosis in FLT3-ITD mutated acute myeloid leukemia (AML) cells and is a potential candidate for research in relapsed/refractory FLT3-ITD positive AML.</p>

Ki11502 is a multi-target receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the activity of PDGFβ/α receptors (with an IC50 of less than 10 nM). It specifically suppresses PDGFβ receptor phosphorylation, proliferation, and proteoglycan synthesis in human vascular smooth muscle cells. Additionally, Ki11502 induces apoptosis and exhibits significant antiproliferative effects against specific leukemia subgroups, including those with Imatinib-resistant mutations. It is particularly suitable for studying the role of PDGF in vascular diseases and the involvement of proteoglycans in atherosclerosis.

PF-06263276 selectively inhibits pan-JAK with IC50: JAK1 (2.2 nM), JAK2 (23.1 nM), JAK3 (59.9 nM), TYK2 (29.7 nM).

FGFR-IN-15 (compound 18i) acts as a pan-FGFR inhibitor, exhibiting potent inhibitory activity against FGFR1-4.

Tandutinib (MLN518) sulfate is an effective and selective inhibitor of FLT3, with an IC50 value of 0.22 μM. It also inhibits c-Kit and PDGFR, displaying IC50 values of 0.17 μM and 0.20 μM respectively. This compound can be utilized in the treatment of acute myeloid leukemia and has the capability to cross the blood-brain barrier.

EGFR/VEGFR2-IN-3 (compound 9) is an effective inhibitor of EGFR and VEGFR-2, demonstrating IC50 values of 0.129 µM for EGFR, 0.142 µM for VEGFR-2, and 3.428 µM for COX-2. This compound exhibits cytotoxic properties and induces cell apoptosis (apoptosis) as well as cell cycle arrest at the G2/M phase.

VEGFR-2-IN-16 (Compound 15b) is a potent inhibitor of VEGFR-2 (IC50: 86.36 nM) that exhibits antitumour effects.

EGFR-IN-149 (Compound 3-OH) is an EGFR inhibitor with an IC50 value of 0.42 nM.

Gamendazole is a novel drug candidate for male contraception. It has been shown to reduce fertility in male rats without affecting testosterone levels.

<p>EGFR-IN-159 (compound 12) is a dihydropyrimidine and a potent EGFR inhibitor with an IC50 of 29.00 nM. It exhibits dose-dependent inhibition of EGFR and HER2. The compound shows cytotoxicity against MCF-7 breast cancer cells and Vero cells with IC50 values of 16.07 μg/mL and 35.98 μg/mL, respectively. EGFR-IN-159 does not cross the blood-brain barrier (BBB) and demonstrates significant anticancer activity.</p>

AFP464 (NSC710464) free base is an active HIF-1α inhibitor (IC50: 0.25 μM) and a potent aryl hydrocarbon receptor (AhR) activator.

BTK inhibitor 18 is a selective, potent, covalent, orally active Btk inhibitor (IC50: 142 nM) that exhibits anti-inflammatory effects.

JAK1-IN-9 (compound 23a) is a potent, selective inhibitor of JAK1, demonstrating an IC50 of 72 nM.

EGFR-IN-130 (compound 14b) is an EGFR inhibitor and an inducer of apoptosis (apoptoosis). It effectively kills HeLa cancer cells by inducing apoptosis.

FGFR2/3-IN-2 (compound 10) is an orally active inhibitor targeting FGFR2 and FGFR3. It exhibits IC50 values of 3.7 nM for FGFR2 and 31.2 nM for FGFR3, with a pre-incubation time of 1 hour. FGFR2/3-IN-2 demonstrates selectivity over FGFR1/4 and other kinases, and does not cause diarrhea or increased serum phosphate in vivo. In the SNU-16 gastric cancer model, FGFR2/3-IN-2 can induce tumor stasis or regression.

(Rac)-PT2399 is a potent and specific inhibitor of hypoxia-inducible factor 2a (HIF-2α)(IC50 of 0.01 μM).

VEGFR2-IN-1 is a VEGFR2 inhibitor with antitumor activity used in the study of breast cancer.