Angiogenèse

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

<p>HER2-IN-8 is an inhibitor of HER-2 that can be used in the study of cancer and inflammation-related diseases.</p>

<p>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.</p>

<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>

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

<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>

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

<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>

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

<p>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>

<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>

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

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

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

<p>XMD-17-51 Trifluoroacetate is a pyrimido-diazepinone compound that regulates protein kinases.</p>

<p>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.</p>

<p>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.</p>

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

<p>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.</p>

<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.<br>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)</p>

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

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

<p>Tyrosine-protein kinase ABL, IC50: 1500 nM</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>

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

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

<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>

<p>VEGFR inhibitor</p>