Angiogenèse

<p>Dacomitinib metabolite M2 is also known as Dacomitinib cysteine conjugate. Dacomitinib inhibits both the wild-type (WT) EGFR and EGFR T790M.</p>

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

<p>Tephrosin induces degradation of of EGFR and ErbB2 by inducing internalization of the receptors, has potent antitumor activities.</p>

<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>PROTACFLT3/CDKs degrader-1 (Compound C3) is an agent that degrades cyclin-dependent kinase (CDK2 with a DC50 of 18.73 nM) and FMS-like tyrosine kinase 3 (FLT3). It induces differentiation in HL-60 cells, achieving a 72.77% differentiation rate at 6.25 nM, and inhibits proliferation of acute myeloid leukemia (AML) cells, with an IC50 ranging from 2.9 to 37 nM. PROTACFLT3/CDKs degrader-1 demonstrates potential for improving the treatment of AML.</p>

<p>AT-533 inhibits Hsp90, HSV, hinders HIF-1α/VEGF/VEGFR-2, Erk1/2, FAK, Akt/mTOR/p70S6K, and blocks tumor growth, angiogenesis, and HUVEC activities.</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>BV02 blocks 14-3-3 interactions, useful in chronic myeloid leukemia research, targets T315I mutant and wild-type Bcr-Abl cells.</p>

<p>EGFRT790M/L858R/ACK1-IN-1 (Compound 21a) is a dual inhibitor targeting EGFRT790M/L858R and ACK1 with IC50 values of 23 nM and 263 nM, respectively. This compound effectively inhibits cell proliferation and exhibits antitumor activity.</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>PROTACBTK Degrader-9 (compound 23) is a potent PROTACs degrader that specifically targets BTK. It effectively downregulates the RANKL-activated BTK-PLCγ2-Ca2+-NFATc1 signaling pathway. Consequently, PROTACBTK Degrader-9 inhibits osteoclastogenesis and reduces alveolar bone resorption in a mouse model of periodontitis.</p>

<p>Syk-IN-4: potent, selective SYK inhibitor, orally bioavailable, IC50=0.31 nM, targets autoimmunity, cancers.</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>AD57, a polypharmacological agent, blocks RET kinase (IC50: 2 nM), disrupts related kinases, and hinders cancerous activities like invasion and proliferation.</p>

<p>SJ988497: PROTAC JAK2 degrader, inhibits CRLF2r cell growth, degrades GSPT1, combines Ruxolitinib, linker, Pomalidomide; researched for ALL.</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>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>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>Phosphopeptide ligand for the src SH2 domain (IC50 = 42 nM); displays 30-fold higher affinity than N-acetyl-O-phosphono-Tyr-Glu-Glu-Ile-Glu (Ac-pYEEIE,).</p>

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

<p>Matuzumab (EMD 72000) is a humanized monoclonal antibody targeting EGFR that can be used to study non-small cell lung cancer.</p>

<p>FLT3-IN-20 (compound 34f) is a potent FLT3 inhibitor, demonstrating IC50 values of 1 nM for FLT3-D835Y and 4 nM for FLT3-ITD.</p>

<p>MS39N (compound 27) serves as the negative control for MS39, capable of binding to EGFR without causing its degradation.</p>

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

<p>EGFR-IN-93 (compound 18) is an allosteric inhibitor of the T790M/L858R double mutant EGFR. It is applicable for research in non-small cell lung cancer (NSCLC).</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>PROTACBTK Degrader-8 (compound 3) is an efficient PROTAC BTK degrader with a linker that can couple with ADC antibodies to form PAC.</p>

<p>PROTAC VEGFR-2 degrader-1 shows minimal VEGFR-2 inhibition &amp; low anti-proliferative effect on EA.hy926 cells.</p>

<p>CG-3-246 is a dual inhibitor targeting FLT3 and BCL-2, with dissociation constants (Kd) of 63 nM and 4.25 nM, respectively. This compound plays a significant role in acute myeloid leukemia research.</p>

<p>PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes.</p>

<p>SNIPER(ABL)-024, a compound that conjugates GNF5 (ABL inhibitor) to an LCL161 derivative (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels,</p>

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

<p>Tyrosine Protein Kinase JAK 2 (Phospho-Tyr8, 9) is a peptide derived from mouse JAK2, specifically composed of amino acids 475 to 491.</p>

<p>PKCε (85-92) (ψεRACK) is a peptide and selective PKCε activator, induces a pro-angiogenic response, promotes FGF-2 cytosolization, regulates VEGF activity.</p>

<p>PRMT5/EGFR-IN-1 (Compound 10p) is an orally active dual inhibitor targeting PRMT5 and EGFR, with IC50 values of 15.47 μM and 19.31 μM, respectively. It demonstrates antiproliferative activity against the A549, MCF7, HeLa, and MDA-MB-231 cell lines. This compound also exhibits favorable pharmacokinetic (PK) and pharmacodynamic (PD) properties in vivo and significantly inhibits the growth of MCF7 orthotopic xenograft tumors.</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>HER2-IN-20 (compound 32) is a potent and selective inhibitor of HER2WT and HER2YVMA, with IC50 values of 49 and 42 nM, respectively. It holds potential for research in non-small cell lung cancer (NSCLC).</p>

<p>FAK PROTAC B5: a degrader with 14.9 nM IC50, strong degradation, anti-growth, good plasma stability, and fair permeability.</p>

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

<p>Coumermycin A1 is a JAK2 signal activator. Coumermycin A1 inhibits DNA Gyrase which thereby inhibits cell division in bacteria.</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>KIT/PDGFRA-IN-1 (compound 19) is an inhibitor targeting the stem cell growth factor receptor (KIT) and platelet-derived growth factor receptor alpha (PDGFRA). Its IC50 values are 2.3 µM for KIT-wt, 12 µM for KIT-D816H, 492 µM for KIT-T670I, 0.8 µM for PDGFRA-wt, 99.9 µM for PDGFRA-D842V, 42.3 µM for PDGFRA-T674I, and 4.3 µM for PDGFRA-G680R. The GR50 values for GIST-T1, T1-a-D842V, and GIST-48B cell lines (gastrointestinal stromal tumor cell lines with PDGFR and KIT mutations) are 12 nM, 8900 nM, and ≥10,000 nM, respectively.</p>

<p>Ranibizumab is a humanized monoclonal antibody fragment designed to target and inhibit vascular endothelial growth factor (VEGF), including VEGF110, VEGF121,</p>

<p>MS9449 is a powerful EGFR PROTAC; Kd: 17 nM (WT), 10 nM (L858R); targets mutant EGFRs via UPS and autophagy; hinders NSCLC cell growth.</p>

<p>ML 2-23 is a potent BCR-ABL degrader operating as a PROTAC, exhibiting selective proteasome-dependent degradation of BCR-ABL within leukemia cells [1].</p>

<p>AST5902 is the active metabolite of Alflutinib.</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>HIF-1 inhibitor-4 (HIF-1 inhibitor-4) is a HIF-1 inhibitor with IC50 of 560 nM.</p>

<p>JAK3-IN-14 is a potent, selective and orally active FLT3 inhibitor, with IC50s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively.</p>

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

<p>ALK-IN-12: potent ALK inhibitor (IC50: 0.18 nM), affects IGF1R and InsR (IC50: 20.3/90.6 nM), potential for cancer therapy.</p>

<p>Mersalyl is an organic mercurial diuretic.</p>

<p>VGX100 is a humanized antibody targeting VEGFC for the study of solid tumors.</p>

<p>EGFR-IN-43 (17c) is a potent EGFR inhibitor with ER antagonist action, tamoxifen/endoxifen+gefitinib linkage, and strong anticancer activity.</p>

<p>Sunitinib D10, a deuterium-enriched version, inhibits VEGFR2 and PDGFRβ tyrosine kinases (IC50: 80 nM/2 nM).</p>

<p>PND-1186 hydrochloride (VS-4718 hydrochloride) is a highly specific, reversible and potent inhibitor of FAK (IC50: 1.5 nM), which can selectively induce</p>

<p>Naphazoline nitrate: α1-adrenergic agonist, induces autophagy, necrosis in cancer cells, inhibits differentiation, treats congestion and eye issues.</p>

<p>Nilotinib D6 is a deuterium labeled Nilotinib which is an orally available inhibitor of Bcr-Abl tyrosine kinase ,and with antineoplastic activity.</p>

<p>BI-4142 is a HER2 inhibitor that inhibits cancer cell proliferation, suppresses her2-dependent cell lines and inhibits downstream signalling.</p>

<p>IBT6A hydrochloride: Ibrutinib impurity, Btk inhibitor IC50: 0.5 nM, used in dimer/adduct synthesis.</p>

<p>SM1-71 is a TAK1 inhibitor that inhibits MKNK2 and RSK2.SM1-71 acts as a kinase probe with anticancer activity.</p>

<p>Erlotinib Hydrochloride inhibits purified EGFR kinase with an IC50 of 2 nM. Erlotinib D6 hydrochloride a deuterium labeled Erlotinib Hydrochloride.</p>

<p>Lck inhibitor 2 blocks tyrosine kinases LCK, BTK, LYN, SYK, TXK with IC50s: Lck 13nM, Btk 9nM/26nM, Lyn 3nM, Txk 2nM.</p>

<p>Ponatinib D8 is a deuterium-enriched, oral multi-kinase inhibitor (Abl, PDGFRα, VEGFR2, FGFR1, Src; IC50s: 0.37-5.4 nM).</p>

<p>KG-548 is a dual inhibitor of ARNT/TACC3 and HIF-1α, inhibiting lactate production, and can be used in cancer research.</p>

<p>SU11652 is an effective and competitive receptor tyrosine kinase (RTK) inhibitor, including VEGFR, FGFR, PDGFR, and Kit.</p>

<p>Tucatinib (Irbinitinib) hemiethanolate is a potent, orally active and selective HER2 inhibitor with an IC50 of 8 nM.</p>

<p>(E/Z)-Zotiraciclib ((E/Z)-TG02) hydrochloride is a potent inhibitor of CDK2, JAK2, and FLT3.</p>

<p>Atinvicitinib, a selective JAK1 inhibitor, blocks cytokine signaling, modulating itch, allergy, and inflammatory responses, immune and therapeutic studies.</p>

<p>Regorafenib D3 is a deuterium labeled Regorafenib. Regorafenib is a multi-targeted receptor inhibitor of tyrosine kinase.</p>

<p>NX-5948 (BTK-IN-24) is a PROTAC-type BTK degrader with anti-inflammatory and anticancer activities, inhibiting B cell activation.</p>

<p>LDN193189 is a BMPI receptor inhibitor, blocking ALK2 and ALK3 effectively, while weak on ALK4, ALK5, ALK7.</p>

<p>Cediranib maleate (AZD2171 maleate) is a VEGFR2 inhibitor that inhibits Flt1, KDR, Flt4, PDGFRα, PDGFRβ, c-Kit.</p>

<p>N-piperidine Ibrutinib hydrochloride is a BTK inhibitor that inhibits WT BTK and C481S BTK , which inhibits the growth and proliferation of cancer cells.</p>

<p>Surfen dihydrochloride (Aminoquinuride dihydrochloride) is a heparin sulfate antagonist with antimicrobial properties and inhibits blockade of signaling.</p>

<p>Gefitinib is an EGFR tyrosine kinase inhibitor, with IC50 of 2-37 nM in NR6wtEGFR cells. Gefitinib D8 is a deuterium labeled Gefitinib.</p>

<p>Ribociclib-d6 is a deuterated compound of Ribociclib (LEE011) for isotope tracing.Ribociclib is an orally available CDK4/6 inhibitor with antitumor activity.</p>

<p>Momelotinib sulfate is an ATP-competitive JAK1/JAK2 inhibitor (IC50: 11 nM/18 nM). It has 10-fold selectivity versus JAK3.</p>

<p>Elsubrutinib (ABBV-105) is a highly active, potent, and selective orally-administered inhibitor of Bruton's tyrosine kinase (BTK). It irreversibly inhibits the catalytic domain of BTK with an IC50 value of 0.18 μM. Elsubrutinib holds potential for the advancement of research on inflammatory diseases.</p>

<p>(3S, 4S)-PF-06459988, a less active S enantiomer, specifically inhibits T790M mutant EGFR with high selectivity.</p>

<p>HIF-IN-1 is a inhibitor of hypoxia-inducible factor, which is associated with tumor and cancer cell proliferation and inhibits HIF-1α protein aggregation.</p>

<p>iHCK-37 (ASN05260065) is an Hck inhibitor with antitumor activity and blocks HIV-1 replication, used in chronic myelogenous leukemia (CML) research.</p>

<p>Ifidancitinib (ATI-50002) is a JAK kinase 1/3 inhibitor used to study autoimmune diseases.</p>

<p>FLT3-IN-16 is a potent FLT3 inhibitor (IC50 = 1.1 μM) for acute myeloid leukemia research.</p>

<p>Tyrphostin 8(4-Hydroxybenzylidenemalononitrile) is a potent GTPase inhibitor that inhibits EGFR kinase with an IC50 of 560 μM.Tyrphostin 8 inhibits protein</p>

<p>QL47 acts as an inhibitor of viral translation and a BTK inhibitor with antiviral activity against dengue virus and can be used in the study of lymphoma.</p>

<p>HIF-1α-IN-2 is a HIF-1α inhibitor with anticancer activity that inhibits the expression of HIF-1α and VEGF, and inhibits cell migration.</p>

<p>Conteltinibtetrahydrochloride (CT-707 tetrahydrochloride) is the tetrahydrochloride form of Conteltinib. It acts as an inhibitor for FAK (IC50=1.6 nM), ALK, and Pyk2. When used in combination with Cabozantinib, Conteltinib tetrahydrochloride exhibits a synergistic antitumor effect.</p>

<p>Afatinib D6 (BIBW 2992 D6) is a deuterium-labeled Afatinib. Afatinib is an irreversible EGFR family inhibitor.</p>

<p>Asciminib (ABL001) hydrochloride is a selective and potent mutant BCR-ABL1 inhibitor that inhibits Ba/F3 cell growth (IC50: 0.25 nM).</p>

<p>Telatinib mesylate is a potent, orally active inhibitor of VEGFR2 (IC50: 6 nM), VEGFR3 (IC50: 4 nM), PDGFα (IC50: 15 nM) and c-Kit (IC50: 1 nM).</p>

<p>Rociletinib hydrobromide is an orally delivered inhibitor of the mutant form of EGFR kinase (Kis: 21.5 nM and 303.3 nM for EGFR L858R/T790M and EGFR WT).</p>

<p>Ilunocitinib is a non-selective and orally active Janus kinase (JAK) inhibitor for pruritus and atopic dermatitis caused by atopic dermatitis in dogs.</p>

<p>(Z)-Orantinib, oral ATP-competitive blocker for Flk-1/KDR, PDGFRβ, FGFR1 (IC50: 2.1, 0.008, 1.2 μM), is a strong antiangiogenic, antitumor drug.</p>

<p>Tirbanibulin is an inhibitor of Src that targets the peptide substrate site of Src (GI50: 9-60 nM in cancer cell lines).</p>

<p>Disitamab (RC48-0) is a humanized anti-HER2 monoclonal antibody used in ADC synthesis.</p>

<p>Tetrac (Tetraiodothyroacetic acid) is a derivative of L-thyroxine (T4), a thyroxine integrin receptor antagonist.Tetrac induces antiproliferation by blocking</p>

<p>Erlotinib is a directly acting inhibitor EGFR tyrosine kinase inhibitor with an IC50 of 2 nM for human EGFR. Erlotinib D6 is a deuterium labeled Erlotinib .</p>

<p>PGV-1, an oral Curcumin analog, induces apoptosis by inhibiting COX-2, VEGF, and NF-κB activation.</p>

<p>EW-7195 inhibits ALK5/TGFβR1 (&gt;300x selective over p38α) with 4.83 nM IC50, blocking TGF-β1 signaling, EMT, and breast cancer lung metastasis.</p>

<p>Imatinib D4 is a deuterium-labeled Imatinib. Imatinib is an orally bioavailable tyrosine kinases inhibitor that selectively inhibits BCR/ABL, PDGFR, v-Abl, and c-kit kinase activity.</p>

<p>Poseltinib is an oral, irreversible BTK inhibitor (IC50 1.95 nM) with higher selectivity over BMX, TEC, and TXK, blocking BCR, FcR, and TLR signaling.</p>

<p>Bleximenib oxalate (Menin-MLL inhibitor 24 oxalate) is a menin-MLL inhibitor that blocks the binding of the menin-KMT2A complex to chromatin at gene promoters.</p>

<p>Itacitinib adipate: oral JAK1 inhibitor, tested in phase II myelofibrosis trial.</p>