Angiogenèse

<p>Potent PROTAC EGFR degrader 2; IC50: 4.0 nM, DC50: 36.51 nM; inhibits cell growth; for NTR-responsive synthesis.</p>

<p>MLK3-IN-1 (Compound 37) is a selective inhibitor of mixed-lineage kinase 3 (MLK3) with an IC50 of less than 1 nM. It also inhibits FAK with an IC50 of 15.5 μM. In both murine and human liver microsomes, MLK3-IN-1 demonstrates excellent metabolic stability.</p>

<p>Apoptosisinducer 35 (Compound 6) is a multi-target inhibitor that reduces the expression of EGFR, AKT, ERK, and P38-MAPKα. It suppresses the proliferation of cancer cells A549 and Jurkat, induces cell cycle arrest at the S phase, and triggers apoptosis (cell death).</p>

<p>Syk signaling is key in lupus. Syk inhibitors reduce inflammation and sepsis severity in FcgRIIb-/- mice, lowering cytokines and organ damage.</p>

<p>MS9427 TFA: PROTAC EGFR degrader, Kd 7.1 nM (WT), 4.3 nM (L858R), targets mutant EGFR, inhibits NSCLC cell growth, for cancer research.</p>

<p>Syk-IN-4: potent, selective SYK inhibitor, orally bioavailable, IC50=0.31 nM, targets autoimmunity, cancers.</p>

<p>AD57, a polypharmacological agent, blocks RET kinase (IC50: 2 nM), disrupts related kinases, and hinders cancerous activities like invasion and proliferation.</p>

<p>PROTAC FAK degrader 1 is a selective and potent degrader of focal adhesion kinase (Fak) (IC50 of 6.5 nM).</p>

<p>BMS-599626 2HCL (AC480 2HCl) is a BMS-599626 derivative.</p>

<p>JAK1/TYK2-IN-1 is a dual inhibitor of TYK2 and JAK1 ( IC 50 = 29 and 41 nM respectively).</p>

<p>Potent, selective oral PROTAC BTK Degrader-1; IC50: 34.51 nM (WT), 64.56 nM (BTK-481S); reduces BTK protein, inhibits tumors.</p>

<p>PLM-101 is an anticancer compound orally active against acute myeloid leukemia by targeting FLT3 and RET.</p>

<p>PTD10, a highly potent PROTAC BTK degrader, exhibits a DC50 of 0.5 nM and a KD of 2.28 nM.</p>

<p>VEGFR/PARP-IN-1 (Compound 14b) is a dual inhibitor of VEGFR and PARP with IC50 values of 191 nM and 60.9 nM, respectively.</p>

<p>EGFR-IN-22: potent for EGFR (IC50: 4.91 nM) &amp; L858R/T790M/C797S mutation (IC50: 0.54 nM).</p>

<p>A unique collection of 1353 proangiogenic and antiangiogenic compounds for new targets identification, research in mechanisms of angiogenesis, and high</p>

<p>EGFR/CDK2-IN-2 (compound 6a) serves as a dual inhibitor targeting both EGFR and CDK-2, exhibiting IC50 values of 19.6 nM and 87.9 nM, respectively.</p>

<p>SNIPER(ABL)-050 is a chemical compound that combines Imatinib, an ABL inhibitor, with MV-1, an IAP ligand, using a linker.</p>

<p>Compound 5K (Multi-target kinase inhibitor 2) is a multi-targeted kinase inhibitor demonstrating activity against EGFR, Her2, VEGFR2, and CDK2 with IC50 values</p>

<p>HAT-SIL-TG-1&amp;AT: a hypoxia-activated JAK inhibitor that curbs HEL cell growth &amp; STAT3/5 phosphorylation in tumors.</p>

<p>EGFR-IN-42 (17b) is a potent EGFR inhibitor with nanomolar efficacy, merging tamoxifen/endoxifen and gefitinib, exhibiting enhanced anti-cancer action.</p>

<p>Compound 13b, a potent EGFR degrader, inhibits and induces apoptosis in NSCLC cells with a DC50 of 13.2 nM.</p>

<p>VSLRGDTRG is a synthetic peptide derived from the RGD motif in cadherin17 (CDH17) that binds to the α2β1 integrin, activating its signaling pathways. By promoting high-affinity conformational changes in β1 integrins through the RGD motif, VSLRGDTRG enhances cell adhesion and the phosphorylation of FAK and ERK1/2, thereby driving tumor proliferation and metastasis. This peptide is useful for research on cancers expressing CDH17, such as colorectal and pancreatic cancer.</p>

<p>HIF-1 inhibitor-4 (HIF-1 inhibitor-4) is a HIF-1 inhibitor with IC50 of 560 nM.</p>

<p>Zilurgisertib (INCB-000928) is a selective and potent ALK 2 inhibitor for the study of cancer and MF anemia.</p>

<p>MY-1576 is a FAK inhibitor with an IC50 of 8 nM. It activates the Hippo pathway, thereby inhibiting YAP/TAZ regulation. Additionally, MY-1576 effectively suppresses tumor growth in the KYSE30 xenograft mouse model, demonstrates good safety, and efficiently downregulates FAK autophosphorylation and YAP/TAZ levels in vivo.</p>

<p>A unique collection of 1336 HIF-1 related small chemicals can be used for drug discovery in ischemic disease and cancer and related mechanism studies；</p>

<p>AG1478 HCl is an epidermal growth factor receptor protein inhibitor.</p>

<p>CNX-500: covalent Btk inhibitor linked to biotin, IC50 0.5 nM, low effect on EGFR and Src kinases.</p>

<p>Sorafenib D4 is deuterium-labeled Sorafenib, a multi-kinase inhibitor (Raf-1, B-Raf, VEGFR-3) with IC50s: 6, 20, 22 nM.</p>

<p>Ibrutinib dimer is an impurity of Ibrutinib. IIbrutinib dimer is a Dimer of Ibrutinib. Ibrutinib is an irreversible Btk inhibitor (IC50: 0.5 nM).</p>

<p>MPT0B390 is an inhibitor of HDAC and a TIMP3 inducer inhibiting tumor growth, metastasis, and angiogenesis.</p>

<p>CEP-5214: Powerful pan VEGF-R tyrosine kinase inhibitor; IC50: 16nM (R1), 8nM (R2), 4nM (R3); effective in cells.</p>

<p>Arg-IN-1 is a selective covalent inhibitor targeting Arginine (Arg), with IC50 values of 9.7 nM and 30.4 nM for FGFR2 and FGFR3, respectively. This compound is designed to potentially avoid the off-target toxicity of FGFR1/4 and overcome acquired resistance, offering potential in cancer therapies targeting FGFR.</p>

<p>Bevasiranib is a siRNA targeting VEGF production, key in choroidal neo-vascularization and wet AMD.</p>

<p>EGFR/HER2/DHFR-IN-3 (compound 4c) serves as an efficacious dual inhibitor specifically targeting EGFR/HER2, exhibiting IC50 values of 0.138 μM for EGFR and 0.</p>

<p>PROTAC EGFR degrader 4 targets mutant EGFR, degrades del19 and L858R/T790M (DC50: 0.51, 126 nM), and inhibits HCC827, H1975 cell growth (IC50: 0.83, 203.1 nM).</p>

<p>DB1113 is a bifunctional kinase degrader, targeting ABL1, ABL2, CDK4, MAPKs, and more for disease research.</p>

<p>GMB-475 is a PROTAC ligand targeting BCR-ABL1 for degradation via E3 ligase recruitment.</p>

<p>SNIPER(ABL)-033, a compound that conjugates HG-7-85-01 (ABL inhibitor) to a LCL161 derivative (IAP ligand) via a linker, effectively reduces BCR-ABL protein</p>

<p>EGFR-IN-78 (compound A5), a 2-aminopyrimidine derivative, serves as a reversible EGFR C797S-TK inhibitor and an apoptosis inducer.</p>

<p>ALK-IN-9 effectively inhibits cell growth with IC50 &lt;0.2 nM for Ba/F3-EML4-ALK, KM12, KG-1.</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>PROTAC BCR-ABL Degrader-1 (compound PROTAC 1), featuring a 2-oxoethyl linker, promotes Bcr-Abl degradation through the ubiquitin-proteasome pathway and</p>

<p>BTK-IN-5 is a covalent inhibitor of Bruton's tyrosine kinase (BTK) designed for the treatment of medical conditions including cardiovascular diseases,</p>

<p>DC-Srci-6649 is a potent and selective inhibitor of c-Src kinase, effectively blocking its phosphorylation and stabilizing it in an inactive conformation.</p>

<p>SNIPER(ABL)-015, a compound that conjugates GNF5 (ABL inhibitor) to MV-1 (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels with a DC50 of 5</p>

<p>Simotinib hydrochloride: selective oral EGFR inhibitor, IC50 19.9 nM, potent anticancer agent.</p>

<p>TYK2activator-1 (16b) is a TYK2 activator with an EC50 value of 1.78 μM. It inhibits JAK2 and JAK3 with IC50 values of 6.8 μM and 6.3 μM, respectively.</p>

<p>PF15 TFA, a PROTAC targeting FLT3 kinase and CRBN, exhibits selective degradation of FLT3-ITD with a DC50 of 76.7 nM.</p>

<p>SI-2, a SRC-3 inhibitor, triggers breast cancer cell death (IC50: 3-20 nM), sparing normal cells.</p>

<p>VEGFR-2-IN-64 (Compound 28) is an inhibitor of VEGFR2 with an IC50 of 27.8 nM. It suppresses the proliferation of cancer cells A549, T-47D, and Caco-2, exhibits anti-migration and anti-colony formation activities in T-47D cells, and induces apoptosis in T-47D cells.</p>

<p>7-Hydroxyneolamellarin A, from Dendrilla nigra, inhibits HIF-1α and VEGF in cancer research.</p>

<p>Tomuzotuximab: fully human, glycoengineered IgG1 anti-EGFR monoclonal antibody with anticancer properties.</p>

<p>AD57 is a potent inhibitor of both c-Src and Abl with IC50 of 0.025 μM and 0.041 μM, respectively.</p>

<p>EGFR-IN-153 (Compound 5l) is an EGFR inhibitor that suppresses the proliferation of MDA-MB-231 cells with an IC50 of 0.73 μM and induces apoptosis. It is applicable for research in breast cancer.</p>

<p>Sotiburafusp alfa is a humanized bispecific fusion protein comprising a VEGFR-1 extracellular domain fragment (129-228, 1-100 in the current sequence) connected</p>

<p>SJF 1521 is an EGFR degrader belonging to the PROTAC class that selectively degrades EGFR while preserving HER2.</p>

<p>PACAP-38 (31-38), human, mouse, rat demonstrates potent, efficacious, and sustained stimulatory effects on sympathetic neuronal NPY and catecholamine production</p>

<p>SNIPER(ABL)-020, a Dasatinib-Bestatin conjugate via linker, inhibits ABL and targets IAP, reducing BCR-ABL protein.</p>

<p>MHES0488A is a selective humanized antibody targeting HER2, with a KD value of 0.8 nM. It constitutes the antibody portion of DHES0815A. Upon cellular internalization, MHES0488A is transported to lysosomes, releasing PBD-monoamide into the nucleus, where it alkylates DNA, inducing DNA damage and apoptosis. It shows potential for research in cancers such as HER2-positive breast cancer and gastric cancer.</p>

<p>VSLRGDTRG acetate is a synthetic peptide of the RGD motif from cadherin17 (CDH17), capable of binding to α2β1 integrin and activating its signaling pathways. It facilitates the high-affinity conformational change of β1 integrin via the RGD motif, enhancing cell adhesion and phosphorylation of FAK and ERK1/2, thereby promoting tumor proliferation and metastasis. VSLRGDTRG acetate is applicable in research on cancers expressing CDH17, such as colon and pancreatic cancers.</p>

<p>EGFR-IN-140 (Compound 31) is an inhibitor of EGFR, effectively targeting both wild-type EGFR and the EGFRL858R/T790M/C797S mutant, with Ki values of 0.95 nM and 2.1 nM, respectively. Additionally, it inhibits EGFRdel19/T790M/C797S in Ba/F3 cells with an IC50 of 56.9 nM and demonstrates antitumor activity in mouse models.</p>

<p>EGFR-IN-83 (Compound 9), an EGFR inhibitor with an IC50 of 2.53 nM, exhibits antiproliferative effects on MCF-7 and MDA-MB-231 cell lines, with respective IC50</p>

<p>JAK 3 inhibitor IV (ZM 39923 hydrochloride) is a JAK1/3 inhibitor with pIC50 of 4.4/7.1, almost no activity to JAK2 and modestly potent to EGFR; also found to</p>

<p>BV02 blocks 14-3-3 interactions, useful in chronic myeloid leukemia research, targets T315I mutant and wild-type Bcr-Abl cells.</p>

<p>SNIPER(ABL)-058, a compound that links Imatinib (ABL inhibitor) with a derivative of LCL161 (IAP ligand) through a linker, effectively decreases BCR-ABL protein</p>

<p>AZ12672857 is an inhibitor of EphB4 with IC50 of 1.3 nM.</p>

<p>hCA/VEGFR-2-IN-3 (compound 8j) is an indolinonylbenzenesulfonamide with potential as a dual inhibitor of cancer-associated hCA IX/XII and VEGFR-2.</p>

<p>TL13-12 is a selective degrader of ALK-PROTAC and inhibits ALK activity (IC50: 0.69 nM).</p>

<p>SJ1008030 (compound 8) formic is a selective JAK2 degrader within the PROTAC class, demonstrating efficacy in inhibiting MHH-CALL-4 leukemia cell growth with an</p>

<p>Varlitinib Tosylate is a selective and potent inhibitor of ErbB1(EGFR) and ErbB2(HER2).</p>

<p>EGFR-IN-86 (compound 4i), an EGFR inhibitor (IC50: 1.5 nM), demonstrates potent activity against glioblastoma by inducing apoptosis and causing G2/M phase cell</p>

<p>AKN-028 is an orally active and potent FLT3 tyrosine kinase inhibitor ( IC 50 = 6 nM). AKN-028 causes dose-dependent inhibition of FLT3 autophosphorylation.</p>

<p>SNIPER(ABL)-039, conjugating Dasatinib (ABL inhibitor) to LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of</p>

<p>(R)-3-Hydroxy Midostaurin: potent kinase inhibitor, major midostaurin metabolite via CYP3A4, potential AML treatment.</p>

<p>SC209, a STRO-002 metabolite from patent WO2021247798, synthesizes anti-EGFR ADCs.</p>

<p>FDU73 is a potent and selective BTK PROTAC degrader with a DC50 of 2.9 nM in JeKo-1 cells. It inhibits tumor cell proliferation and exhibits antitumor activity.</p>

<p>FAK-IN-27 (compound 8A) is a potent and selective inhibitor of FAK, with an IC50 of 4.968 nM. It effectively inhibits the proliferation of H1299 cells, with an IC50 of 0.28 μM, and is applicable for research in non-small cell lung cancer (NSCLC).</p>

<p>Multi-kinase-IN-5 (compound 15c) is a multi-kinase inhibitory agent that shows significant inhibition against a range of protein kinases including RET, KIT,</p>

<p>SJ988497: PROTAC JAK2 degrader, inhibits CRLF2r cell growth, degrades GSPT1, combines Ruxolitinib, linker, Pomalidomide; researched for ALL.</p>

<p>hCA/VEGFR-2-IN-1 (compound 13a) is a potent dual inhibitor targeting both Carbonic Anhydrase (CA) IX/XII and Vascular Endothelial Growth Factor Receptor 2 (</p>

<p>Lyso-Monosialoganglioside GM3 (Lyso-GM3) is an analog of Ganglioside GM3 with antitumor properties. It inhibits the increase in EGFR kinase activity induced by EGF in A431 epithelial cancer cells.</p>

<p>Axltide mimics mouse Insulin receptor substrate 1, amino acids 979-989 with sequence KKSRGDYMTMQIG.</p>

<p>SOS1/EGFR-IN-2 (Compound 4) functions as a dual inhibitor of SOS1 and EGFR, exhibiting IC50 values of 8.3 and 14.6 nM, respectively. It demonstrates significant antiproliferative effects on cancer cells harboring various KRAS mutations.</p>

<p>JAK-IN-15 is a JAK inhibitor. WO2016119700A1 (Compound 15).</p>

<p>VEGFR2/HDAC1-IN-1 (compound 13) is a potent dual inhibitor of VEGFR-2 and HDAC, with IC50 values of 57.83 nM for VEGFR-2 and 9.82 nM for HDAC.</p>

<p>Trastuzumab envedotin (DP303c) is an antibody-drug conjugate (ADC) targeting the human epidermal growth factor receptor 2 (HER2). It consists of the anti-HER2 antibody DP001 linked to the microtubule polymerization inhibitor MonomethylauristatinE (MMAE) through a cleavable linker. This compound is utilized in research involving HER2-positive solid tumors such as breast cancer, colorectal cancer, and gastric cancer.</p>

<p>TL13-112 is a selective degrader of ALK-PROTAC and inhibits ALK activity (IC50: 0.14 nM).</p>

<p>Compound 8g (hCA/VEGFR-2-IN-2) is an indolinonylbenzenesulfonamide identified as a potential dual inhibitor targeting cancer-associated isozymes hCA IX/XII and</p>

<p>LC-MB12 is a PROTAC FGFR2 compound that degrades FGFR2 and can be used to study gastric cancer.</p>

<p>Coumermycin A1 is a JAK2 signal activator. Coumermycin A1 inhibits DNA Gyrase which thereby inhibits cell division in bacteria.</p>

<p>SA-PA, a self-assembled intracellular PROTAC leveraging azide-alkyne click chemistry, selectively degrades VEGFR-2, PDGFR-β, and EphB4 proteins within U87 cells</p>

<p>K882 (Compound 4e) is an Src inhibitor with a KD of 0.315 μM. It induces apoptosis and inhibits XIAP and Survivin. Additionally, K882 blocks the activation of the PI3K/Akt/mTOR, Jak1/Stat3, and Ras/MAPK signaling pathways. K882 exhibits antitumor activity against non-small cell lung cancer.</p>

<p>DSPE-PEG5000-GE11 is a PEG compound composed of DSPE and the EGFR-targeting peptide (GE11). GE11 is applicable for cancer cells with EGFR overexpression. DSPE-PEG5000-GE11 is utilized in drug delivery.</p>

<p>FLT3-IN-28 (Compound 12y) is an orally active FLT3 inhibitor with antitumor properties. It selectively targets cancer cells with FLT3 internal tandem duplication (ITD) mutations, demonstrating IC50 values of 85, 290, 130, 65, and 220 nM against BaF3-FLT3-ITD, BaF3-TEL-VEGFR2, MV4-11, MOLM-13, and MOLM-14 cell lines, respectively. These lines include acute myeloid leukemia (AML) cells harboring FLT3-ITD mutations such as MV4-11 and MOLM-13/14. The compound also reduces phosphorylation levels of FLT3 and STAT5 in MOLM-13 cells, leading to cell cycle arrest and apoptosis. With an oral bioavailability of 19.2% in SD rats, FLT3-IN-28 extends survival in a dose-dependent manner in MOLM-13 xenografted NSG mouse models. It holds promise for research in FLT3-ITD-related cancer studies.</p>

<p>FAK-IN-24 (Compound 9f) is a potent FAK inhibitor with an IC50 of 0.815 nM. It induces DNA damage and apoptosis, and exhibits activity against glioblastoma. FAK-IN-24 effectively inhibits proliferation of glioblastoma cell lines U87-MG (IC50= 15 nM) and U251 (IC50= 20 nM), and suppresses tumor growth in U87-MG xenograft models.</p>

<p>FLT3/VEGFR2-IN-1 (Compound 26) is a potent inhibitor of FLT3, VEGFR2, and HDAC, exhibiting IC50 values of 14.5 nM, 3.9 nM, and 30.8 nM against FLT3, VEGFR2, and HDAC1, respectively. It effectively inhibits the phosphorylation of STAT3 and ERK1/2, as well as the proliferation of leukemia cells. FLT3/VEGFR2-IN-1 demonstrates antitumor activity and is applicable in research on acute myeloid leukemia.</p>

<p>AXL/Angiokinase-IN-1 (compound 11b) is an inhibitor of AXL/triple angiokinase, with an IC50 of 3.75 nM for AXL expression. This compound suppresses epithelial-mesenchymal transition (EMT) in Bxpc-3 cells and prevents metastasis in lung cancer cells. Additionally, AXL/Angiokinase-IN-1 impairs the functions of vascular and fibroblast cells and induces apoptosis in both cancer and fibroblast cells. It is characterized by low toxicity and favorable metabolic stability.</p>

<p>JH-XI-10-02 selectively degrades CDK8 (IC50: 159 nM) through proteasome, sparing CDK8 mRNA and CDK19.</p>