Angiogenèse

<p>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.</p>

<p>M-COPA disrupts Golgi, blocks MET &amp; Arf1 activation, and inhibits angiogenesis via VEGFR &amp; NF-kB pathways.</p>

<p>Compound 26F: potent enzyme inhibitor (IC50=28.2nM), low cytotoxicity (IC50=3.32μM), induces dose-dependent apoptosis in MDA-MB-231, blocks G0/G1 phase.</p>

<p>VEGFR-2-IN-15 (Compound 14b) is a potent inhibitor of VEGFR-2. VEGFR-2-IN-15 inhibits the growth of HepG2 cells in the Pre-G1 phase and induces apoptosis.</p>

<p>ALK-IN-23 inhibits ALK (IC50: 1.6-0.71 nM), hinders cancer cell spread, forms colonies in vitro, and reduces tumors in mice with low toxicity.</p>

<p>BTK-IN-10 is a potent inhibitor of BTK, acting on wild-type BTK (IC50&lt;5 nM) or mutant BTK (C481S) (IC50&lt;5 nM).</p>

<p>VEGFR-2-IN-14 (Compound 5) is a potent inhibitor of VEGFR-2, which inhibits the growth of HepG2 cells in the Pre-G1 phase and induces apoptosis.</p>

<p>NSC381467: Potent, oral EGFR-TK inhibitor with strong antiproliferative effects, promising for cancer research.</p>

<p>AZD0424: oral Src/Abl kinase inhibitor; potential anticancer; induces apoptosis, cell cycle arrest in lymphoma.</p>

<p>JAK1/TYK2-IN-3, orally active, selectively inhibits TYK2 (IC50: 6 nM), JAK1 (37 nM), JAK2 (140 nM), JAK3 (362 nM), and has anti-inflammatory effects.</p>

<p>FAK-IN-3 inhibits FAK, reduces PA-1 cell migration/invasion, and tumor growth, with no major side effects.</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>FGFR1inhibitor-16 (Compound 89) functions as an FGFR1 inhibitor, demonstrating an inhibition rate of 53.00% at a concentration of 50 μM and 24.95% at 10 μM. It is utilized in tumor research.</p>

<p>EGFR/HER2-IN-7: Potent, selective dual inhibitor for MCF-7 cancer; IC50: EGFR 0.18μM, HER2 0.146μM, DHFR 0.907μM.</p>

<p>GNE-431: potent, selective noncovalent Btk inhibitor, IC50=3.2 nM; effective against C481R, T474I, T474M mutants, may counter ibrutinib resistance.</p>

OXA-11 (FAK-IN-16) is a FAK inhibitor with anti-tumor activity, useful for cancer research.

<p>FLT3-ITD-IN-3 (13v) is an orally active inhibitor of FLT3-ITD (internal tandem duplication of FLT3), which works by blocking FLT3 signaling. This inhibition leads to cell cycle arrest in the G0/G1 phase and induces apoptosis. The compound is currently employed in studies related to acute myeloid leukemia (AML).</p>

<p>"JAK-IN-23: oral dual JAK/STAT &amp; NF-κB inhibitor; JAK1 (IC50: 8.9 nM), JAK2 (15 nM), JAK3 (46.2 nM); for IBD research."</p>

<p>EGFR/HER2-IN-5: Irreversible, oral dual EGFR inhibitor, IC50 0.6 nM, targets L858R/T790M mutations, anti-tumor in vivo for lung cancer study.</p>

<p>iBFAR2, an inhibitor of BFAR, restores the CD8+ tumor-resident memory T cell subset against solid tumors. It promotes the binding of JAK2-STAT1 and enhances the phosphorylation of STAT1.</p>

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

<p>Tyrphostin 63 (compound 13) is an epidermal growth factor receptor (EGFR) inhibitor, with an IC50 of 375 μM and a Ki of 123 μM.</p>

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

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

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

<p>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.</p>

<p>FGFR-IN-6 (Compound 5) is an FGFR inhibitor.</p>

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

<p>DA-0157 is an orally active inhibitor targeting EGFR and ALK, designed to overcome resistance mutations in non-small cell lung cancer (NSCLC). It effectively inhibits the proliferation of Ba/F3-EGFR Del19/T790M/C797S (IC50= 6.9 nM), Ba/F3-EGFR WT (IC50= 0.83 μM), Ba/F3-EML4-ALK-L1196M (IC50= 5.5 nM), and Ba/F3-EML4-ALK (IC50= 7.4 nM). Additionally, DA-0157 inhibits CYP2D6 with an IC50 of 5.26 μM and demonstrates antitumor activity in mouse models.</p>

<p>BTK-IN-15: Oral BTK inhibitor, IC50 0.7 nM, induces cancer cell apoptosis, selective with anti-tumor effects.</p>

<p>FLT3/TrKA-IN-1: Potent dual kinase inhibitor for FLT3 &amp; TrKA, promising for AML research.</p>

EGFR-IN-3 is an EGFR inhibitor with antitumor activity.EGFR-IN-3 inhibits EGFRwt-TK, induces apoptosis (cell death), and can block cells in the G2/M phase.

<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>

<p>EGFR/HER2-IN-8 inhibits EGFR, HER2, DHFR (IC50: 0.45, 0.244, 5.669 μM); useful in cancer research, safe and selective.</p>

<p>Milpecitinib (Compound 21a) is a potent and selective Janus tyrosine kinase (JAK) inhibitor with anti-inflammatory properties. It shows promise for research in cancer and inflammatory diseases.</p>

<p>VEGFR-2-IN-25 (compound 5d) is a potent inhibitor of VEGFR-2 (IC50: 12.1 nM).</p>

<p>VEGFR-2-IN-65 (Compound 07) functions as a VEGFR-2 inhibitor. It forms hydrogen bonds with Cys180 and can inhibit tube formation in HUVECs.</p>

<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>

<p>JAK-IN-19 inhibits JAK (pIC50: 7.2, 7.7), less so for VEGFR2 (7.0) and Aurora B (5.8).</p>

<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.</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>

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

<p>Ten01 exhibits a 5.0 nM inhibition of JAK1 kinase.</p>

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

<p>VVD-118313 (5a) is a potent JAK1 inhibitor targeting allosteric cysteine, blocking cytokine signaling for cancer research.</p>

<p>LT-850-166 is a potent inhibitor of FLT3 and has shown efficacy in overcoming a wide range of FLT3 mutations.</p>

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

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

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).

<p>Sacibertinib inhibits Trk, targeting EGFR-TK (EC50 110 nM) &amp; HER2 (EC50 244 nM), with anticancer properties.</p>

<p>EGFR-IN-34 is a low-toxicity, acrylamide derivative antitumor agent that is a potent inhibitor of EGFR.</p>

<p>FAK-IN-23 (Compound II) is an inhibitor of focal adhesion kinase (FAK).</p>

<p>HER2-IN-6, a potent HER2 inhibitor, may target wild/mutant EGFR and HER2-mediated tumors. (Patent WO2021164697A1, compound 11)</p>

<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>

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

<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>

<p>FGFR3-IN-4 is a selective inhibitor targeting FGFR3, demonstrating an IC50 value of under 50 nM.</p>

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

<p>TZEP7 functions as an EGFR kinase inhibitor in cancer cells. It exhibits cytotoxicity and induces apoptosis within these cells. TZEP7 downregulates the anti-apoptotic protein Bcl-2, upregulates the pro-apoptotic protein Bax, and increases caspase levels. This compound holds potential for research in anticancer drug development.</p>

<p>EGFR-IN-48: potent EGFR inhibitor, oral, IC50: 0.193-66.7 nM, blocks EGFR mutants &amp; BaF3/PC-9 cell proliferation.</p>

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

<p>EGFR-IN-23, identified as compound 8 in WO2021244502A1, is a potent EGFR tyrosine kinase inhibitor (TKI) demonstrating an inhibitory concentration (IC50) of 8.</p>

<p>HSN748 is an analog of ponatinib and acts as a multi-kinase inhibitor. It exhibits inhibitory activity against kinases such as FLT3, ABL1, RET, PDGFRα/β, MNK1, and MNK2. HSN748 can suppress the growth of chronic myeloid leukemia and acute myeloid leukemia cell lines, making it a useful compound in leukemia research.</p>

<p>EGFR-IN-24 is a potent inhibitor of EGFR and inhibits EGFR (del19/T790M/C797S) and EGFR (L858R/T790M/C797S).</p>

<p>Multi-kinase-IN-1, a powerful kinase inhibitor, exhibits antitumor properties by inducing cell apoptosis.</p>

<p>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.</p>

<p>HER2-IN-9, an oral HER2 inhibitor (IC50: 0.03 μM), hinders growth and spread of HER2+ breast cancer.</p>

VEGFR/PDGFR-IN-1 (Compound 1) is an inhibitor of VEGFR with an IC50 of 0.4 μM. It can inhibit angiogenesis in HUVEC cells and holds promise for impeding tumor growth and metastasis.

<p>BTK-IN-7 is a potent inhibitor for BTK with 4.0 nM IC50, highly selective over ITK and EGFR, showing strong antitumor activity.</p>

<p>LSD1/EGFR-IN-1 (compound L-1) is an effective inhibitor of LSD1, EGFRT790M/L858R, and EGFRL858R/T790M/C797S, with IC50 values of 6.24, 2.06, and 5.01 μM, respectively. This compound plays a significant role in cancer research.</p>

<p>EGFR/HER2-IN-6 is a dual inhibitor of EGFR, HER2, and DHFR with IC50s: 0.122, 0.078, and 0.585 μM, showing anticancer potential and selectivity.</p>

<p>HER2-IN-21 (compound 657994) is an inhibitor of the human epidermal growth factor receptor 2 (HER2) with an IC50 value of 3.85 μM.</p>

<p>FGFR4-IN-6: covalent, reversible FGFR4 blocker, 5.4 nM IC50, good oral bioavailability, reduces Hep3B2.1-7 tumors in mice, low toxicity.</p>

<p>Protein kinase inhibitor 10 is a protein kinase inhibitor with IC50 values of 28.9 μM, 13.6 μM, and 2.41 μM for TAM receptors, FAK, and KIT, respectively. It can inhibit abnormal and excessive cell proliferation, showing potential for research in the field of cancer treatment.</p>

<p>VEGFR-2-IN-26 inhibits VEGFR-2 (IC50: 15.5 nM), combating various cancers' cell growth.</p>

<p>FGFR4-IN-9 is a selective inhibitor of FGFR4 (IC50: 75.3 nM) that effectively inhibits the growth and angiogenesis of hepatocellular carcinoma cells.</p>

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

<p>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>

<p>DualCathepsinL/JAK-IN-1 (Compound A8) serves as a dual inhibitor of Cathepsin L (CTSL) and JAK, exhibiting IC50 values of 0.68 μM for CTSL and 337.1 nM, 5.251 nM, 27.29 nM, and 172.6 nM for JAK1/2/3 and TYK2, respectively. This compound effectively prevents the activation of MAPK, NF-κB, and JAK/STAT signaling pathways, leading to significant anti-inflammatory therapeutic effects. DualCathepsinL/JAK-IN-1 is applicable in research on acute lung injury (ALI).</p>

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

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

<p>EGFR-IN-17: potent, selective EGFR inhibitor, IC50 of 0.2 nM, overcomes C797S drug resistance.</p>

<p>E7090 succinate inhibits FGFR1, FGFR2, and FGFR3 with IC50: 0.71, 0.50, 1.2 nM; less so FGFR4 at 120 nM.</p>

<p>ALK-IN-31 (Compound Ld-10) is an orally active ALK inhibitor with an IC50 of 1135 nM. It demonstrates excellent antiproliferative activity against lung cancer cells H2228, with an IC50 value of 1.35 μM. ALK-IN-31 induces apoptosis and arrests cell proliferation at the G0/G1 phase by affecting mitochondrial function. It exhibits antitumor effects by downregulating the expression of p-AKT and p-mTOR in the PI3K-AKT-mTOR signaling pathway downstream of ALK. This compound is applicable for research into non-small cell lung cancer (NSCLC).</p>

<p>CLM3, a pyrazolopyrimidine derivative, functions as a multitargeted tyrosine kinase inhibitor. It exhibits antiproliferative and proapoptotic activities on endothelial and cancer cells, activities that are synergistically enhanced by SN38. The primary mechanism of action for CLM3 involves the inhibition of phosphorylation in tyrosine kinases such as VEGFR-2, EGFR, and RET, along with their associated signaling pathways.</p>

SYHA1815, an orally active RET inhibitor (IC50=0.9 nmol/L), demonstrates antitumor activity. It exhibits greater selectivity for RET over KDR (IC50=15.9 nmol/L). SYHA1815 operates by downregulating c-Myc, arresting the G1 cell cycle, and inhibiting RET-driven cell proliferation.

<p>Protein Kinase Inhibitor 12 (compound 1-91) is protein kinase inhibitor,PIM-1, CDK-2, GSK-3, and SRC mammalian protein kinases.</p>

<p>Anticancer agent 69 targets PC3 cells (IC50=26 nM), raises ROS, lowers EGFR, and induces apoptosis.</p>

<p>Multi-kinase inhibitor 3 (compound 12) is an orally active and effective multikinase (multikinase) inhibitor, demonstrating potent IC50 values against FLT1/VEGFR1, KDR/VEGFR2, FLT4/VEGFR3, FLT3, PDGFRα, and PDGFRβ, at 1.59, 1.23, 1.19, 0.59, 0.22, and 1.15 nM respectively. This compound exhibits anti-proliferative and anticancer activities.</p>

<p>Antiallergic agent-1, an Src family kinase inhibitor, is a new and valuable lead compound with potential as an anti-allergic agent.</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>SILA-123, an inhibitor of FLT3 (FLT3-WT: IC50=2.1 nM; FLT3-ITD: IC50=1.0 nM), induces cell apoptosis by hindering the cell cycle progression at the G0/G1 phase through the suppression of FLT3 phosphorylation and its downstream signaling pathways. This compound is utilized in the study of acute myeloid leukemia.</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>I194496 is an effective inhibitor of cystathionine γ-lyase (CSE) with an IC50 value of 0.79 mM. It inhibits the growth of human TNBC cells by dual targeting the PI3K/Akt and Ras/Raf/ERK pathways. Additionally, I194496 suppresses the metastasis of human TNBC cells by downregulating the Anxa2/STAT3 and VEGF/FAK/Paxillin signaling pathways.</p>

<p>JAK3/BTK-IN-4, a dual inhibitor for JAK3/BTK, shows synergy in autoimmune disease treatment. (Patent WO2021147953A1, compound 003)</p>

<p>FAK-IN-6: Potent FAK inhibitor (IC50=1.415 nM), anti-cancer, for pancreatic studies.</p>

<p>Compound 8b inhibits VEGFR-2/DHFR, combats various bacteria, and fights cancer cells.</p>

<p>YSY01A is a proteasome inhibitor that suppresses cancer cell survival by inducing apoptosis (Apoptosis). It demonstrates IC50 values against various cell lines such as HEK293T, A549, MCF-7, MGC-803, and PC-3M with values of 51.01, 9.21, 5.21, 8.9, and 35.4 nM respectively. Additionally, YSY01A serves as a degrader of gp130 and JAK2, eliminating constitutive STAT3 signaling in human A549 lung cancer cells by downregulating gp130 and JAK2. YSY01A holds potential for research in cancer therapeutics.</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>

Multi-kinase inhibitor 4 (compound 14) serves as an orally effective inhibitor targeting FLT1, KDR, FLT3, FLT4, PDGFRα, and PDGFRβ, exhibiting IC50 values of 1.97 nM, 1.04 nM, 0.33 nM, 1.44 nM, 0.18 nM, and 0.89 nM respectively. This compound plays a crucial role in cancer research.

<p>CEE321 is an effective pan-JAK inhibitor with an IC50 of 54 nM. It effectively inhibits biomarkers associated with atopic dermatitis.</p>

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

ALKBH5-IN-3 (Compound 20m) is a selective ALKBH5 inhibitor (IC50=21 nM), effectively stabilizes ALKBH5 in HepG2 cells and elevates m6A levels in intact cells.

<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>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>

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.