Angiogenèse

FGFR1inhibitor-17 (Compound 92) is a potent inhibitor of FGFR1, with promising applications in cancer research.

TrxR/EGFR-IN-1 (Compound L1Au2) is a TrxR/EGFR inhibitor with activity against both gefitinib-sensitive and -resistant lung cancer, effectively suppressing tumor proliferation and promoting apoptosis. It enhances GPX4 degradation through autophagosome-lysosome and proteasome pathways, leading to ferroptosis. Additionally, it induces endoplasmic reticulum stress and triggers immunogenic cell death, making it applicable for studies on gefitinib-resistant lung cancer.

<p>Tyrosine kinase-IN-9 (Compound B) is an inhibitor of c-Abl. It is useful for studying neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.</p>

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.

<p>TGF-βRI inhibitor 3 (Compound 9ac) is a selective inhibitor of TGF-β that effectively suppresses the TGF-β signaling pathway. It exhibits IC50 values of 13 μM for c-Src kinase and 0.63 μM for ALK5 kinase.</p>

<p>Lirucitinib is a JAK inhibitor known for its anti-inflammatory properties.</p>

<p>LNK01004 is a JAK inhibitor that exhibits potent inhibitory effects on JAK1 (IC50: 10 nM), JAK2 (IC50: ＜0.51 nM), and TYK2 (IC50: 1.0 nM). It can concurrently inhibit multiple cytokine-induced p-STAT signaling pathways and is applicable for research on diseases such as atopic dermatitis.</p>

EGFR-IN-147 (compound ID-5841161) is a potent EGFR inhibitor, demonstrating a 14% inhibition rate at a concentration of 1μM. It holds promise for cancer research applications.

(Rac)-Ibrutinib alkyne (Compound 8) is a Btk inhibitor with an IC50 of 0.72 nM. This compound effectively inhibits B cell receptor signaling functions, with an IC50 of 9 nM for calcium flux inhibition in Ramos cells. (Rac)-Ibrutinib alkyne is applicable in research on diseases such as rheumatoid arthritis.

EGFR-IN-135 (compound 3d) is an EGFR inhibitor with an IC50 value of 0.086 µM. It inhibits cell growth and arrests the cell cycle in the S phase in breast cancer cell lines.

HPK1-IN-61 (Compound 1) serves as an inhibitor of hematopoietic progenitor kinase 1 (HPK1) with a Ki of 0.4 nM, and also inhibits Abl with an IC50 of less than 0.51 nM. Additionally, HPK1-IN-61 displays inhibitory activity against LCK, with an IC50 of 24 nM.

WZH-15-125 is a potent ALK inhibitor capable of overcoming resistance, particularly with complex ALK mutations. It exhibits an IC50 of 101.7 nM against the highly recalcitrant Lorlatinib-resistant G1202R/L1196M mutation. Additionally, WZH-15-125 can serve as a PROTAC target protein ligand for synthesizing PROTACWZH-17-002. This compound is applicable in non-small cell lung cancer research.

Tuspetinib (HM43239) dihydrochloride is a selective FLT3 inhibitor with oral bioactivity, exhibiting IC50 values of 1.1 nM for FLT3 wild type, 1.8 nM for FLT3ITD mutant type, and 1.0 nM for FLT3D835Y mutant type. As a reversible type I inhibitor, it directly suppresses FLT3 kinase activity and modulates p-STAT5, p-ERK, SYK, JAK1/2, and TAK1. Tuspetinib dihydrochloride inhibits the proliferation of leukemia cells and induces apoptosis (apoptosis).

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>EGFR-IN-125 (example 37) is a potent EGFR inhibitor with IC50 values of &lt;0.3 nM for EGFR(d746-750/T790M/C797S), 0.52 nM for EGFR(L858R/T790M/C797S), 0.5 nM for EGFR(d746-750/C797S), 0.69 nM for EGFR(L858R/C797S), and 0.92 nM for EGFR (wild type).</p>

RET-IN-14 inhibits RET (IC50: <0.51-9.3 nM) & BTK (C481S) (IC50: 9.2-15 nM), promising for tumor research.

CEP-18770: oral proteasome inhibitor; blocks NF-kappaB; may cause cancer cell apoptosis; less toxic than bortezomib in normal cells.

Ifebemtinib (tosylate) (BI-853520 (tosylate); IN-10018 (tosylate)) is a highly selective PTK2 kinase inhibitor with anti-tumor properties. It inhibits FAK autophosphorylation in prostate cancer cells and suppresses spheroid formation and in situ tumor growth in vivo. Ifebemtinib (tosylate) is applicable in cancer research, including studies on solid tumors, breast cancer, and malignant pleural mesothelioma.

EGFRligand-14 serves as an EGFR ligand and is utilized in the synthesis of SJF-1521.

VEGFR-2-IN-38 (compound 3) acts as a potential inhibitor of the vascular endothelial growth factor receptor-2 [1].

N-Deshydroxyethyl Dasatinib-C3-NH2 is a target protein ligand-linker conjugate, comprising an LCK ligand and a PROTAC linker, designed to recruit E3 ligase. It is utilized in the synthesis of [PROTACSJ11646].

EGFR-IN-58 is a potent, selective, ATP-competitive inhibitor of EGFR. EGFR-IN-58 exhibits significant cytotoxicity against melanoma, colon and blood cancers.

HBI-2375 (HYBI-084) is a selective inhibitor that penetrates the blood-brain barrier and is orally active, targeting the MLL1-WDR5 interaction. It inhibits WDR5 with an IC50 of 4.48 nM and demonstrates antiproliferative activity in MV4;11 leukemia cells with an IC50 of 3.17 µM. Furthermore, HBI-2375 disrupts histone methyltransferase activity in cancer cells and is useful for researching leukemia, glioma, and glioblastoma.

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

BTK-IN-16 is a potential inhibitor of wild-type BTK and C481S mutants.BTK-IN-16 can be used to study various autoimmune diseases and cancers caused by BTK.

EGFRLigand-Linker Conjugates 1 is a Target Protein Ligand-Linker Conjugate comprising an EGFR ligand and a PROTAC linker, designed to recruit the E3 ligase. It is used in the synthesis of PROTACEGFRdegrader 3.

PROTACHer3-binding moiety 2 is an inhibitor of Her3. It is applicable in the synthesis of PROTACHer3 Degrader-8.

G-744 is a selective and orally active inhibitor of Btk (IC50: 2 nM).

TAS05567 is a potent, highly selective, and ATP-competitive Syk inhibitor (IC50: 0.37 nM).

<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>

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

FLT3-IN-32 is a potent FLT3 inhibitor with high selectivity, effectively suppressing FLT3 activating mutations and inducing apoptosis. It demonstrates good tolerance in non-tumor-bearing mice. In NOD/SCID mice loaded with MV4-11 cells, FLT3-IN-32 exhibits outstanding antitumor efficacy, significantly extending mouse survival. FLT3-IN-32 is applicable for acute myeloid leukemia research.

UNC9750 is an inhibitor of inositol phosphate multikinase (IPMK), with IC50 values of 31.6 nM for IPMK and 374 nM for IP6K2. It effectively suppresses the accumulation of InsP5, a direct product of IPMK kinase activity, without affecting InsP6 or InsP7 levels. Additionally, UNC9750 inhibits over 75% of the activity of four kinases: DAPK1, DYRK1B, PDGFR, and KDR. This compound is applicable in glioblastoma research.

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.

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

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.

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.

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

Ibrutinib is a selective, irreversible Btk inhibitor (IC50: 0.5 nM). Ibrutinib Racemate is the racemate of Ibrutinib.

<p>PM-8002 is a bispecific antibody that targets PD-L1 and VEGF-A. It is applicable for research on solid tumors.</p>

PCI 45227 is an active metabolite of the Bruton's tyrosine kinase inhibitor ibrutinib .1PCI 45227 is formed from ibrutinib by the cytochrome P450 (CYP) isoform CYP3A. 1.Veeraraghavan, S., Viswanadha, S., Thappali, S., et al.Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: Application to a pharmacokinetic studyJ. Pharm. Biomed. Anal.107151-158(2015)

Imbotolimod, a humanized monoclonal antibody of the immunoglobulin G1-kappa class, exhibits both anti-ERBB2 and antineoplastic activities.

Tyrosine-protein kinase ABL, IC50: 1500 nM

<p>HMBD-001 is a humanized IgG1 monoclonal antibody inhibitor that targets HER3. By inhibiting the dimerization of HER3, HMBD-001 suppresses the growth and proliferation of tumor cells. It holds potential for research in cancer treatments, specifically for pancreatic cancer and non-small cell lung cancer.</p>

<p>Nimotuzumab (powder) is a humanized IgG1 monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR), possessing a dissociation constant (KD) of 0.21 nM. It blocks the binding to its ligand by targeting the extracellular domain of EGFR. Nimotuzumab exhibits strong antitumor activity by inducing both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), exerting cytolytic effects on target tumors.</p>

ENMD-2076 is an orally active kinase inhibitor. It also has antiangiogenic and antiproliferative mechanisms of action.

XMU-MP-3 is a robust, non-covalent inhibitor of BTK, exhibiting exceptional potency with IC50 values of 10.7 nM and 17.0 nM for BTK WT and BTK C481S mutation, respectively, in the presence of 10 μM ATP. Moreover, XMU-MP-3 elicits apoptosis.

(3R,4S)-Tofacitinib, the less active enantiomer of Tofacitinib, is a JAK3 inhibitor with an IC50 of 1 nM.

<p>Desidustat is an inhibitor of HIF hydroxylase.</p>

Olmutinib (BI1482694) is a Novel Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

PF-03814735 is a novel, potent and reversible inhibitor of Aurora A/B with IC50of 0.8 nM/5 nM, is less potent to Flt3, FAK, TrkA, and minimally active to Met and FGFR1. Phase 1.

<p>Duligotuzumab (MEHD-7945A) is a bispecific humanised IgG-κ monoclonal antibody targeting HER3 and EGFR, solid tumours, head and neck cancer,colorectal cancer.</p>

<p>Applications 3,3',4,4'-Tetrabromobiphenyl is multi-persistent organic pollutants analyzed in breast milk of first time mothers. An environmental pollutant that affects copper and molybdenum metabolism in rats. Also, it is derived from 1-Bromo-2- nitrobenze (B686175), which is an organic building block used for the synthesis of various pharmaceutical compounds. It is an intermediate for the synthesis of novel Diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity.<br>References Tlustos, C., et al.: Organohalogen Compd., 75, 1185-1188 (2013); Salman, K. N., et al.: Environ. Sci. Pollut. R., 21, 6400-6409 (2014); Dao, P., et al.: Bioorg. Med. Chem. Lett., 23, 4552 (2013);<br></p>

VEGFR inhibitor