Angiogénesis

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

<p>EGFR/BRAF-IN-1 inhibits EGFR/BRAF (BRAFV600E IC50: 45 nM, GI50: 35 nM) and has antioxidant properties.</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>SJ-C1044 is an orally effective pan-RAF inhibitor demonstrating immunomodulatory and antitumor activities. It targets wild-type BRAF, wild-type CRAF, and BRAF(V600E) with IC50 values of 331, 257, and 187 nM, respectively. SJ-C1044 suppresses tumor cell proliferation by inhibiting kras activation and MEK-ERK phosphorylation. Additionally, it shows inhibition of VEGFR2, TIE2, and CSF1R, with IC50 values of 100, 23, and 235 nM respectively. The compound enhances the tumor immune microenvironment through inhibition of angiogenesis and modulation of macrophage function. SJ-C1044 is applicable for research in colorectal cancer.</p>

FLT3/TrKA-IN-1: Potent dual kinase inhibitor for FLT3 & TrKA, promising for AML research.

<p>FLT3/ITD-IN-1 inhibits FLT3-ITD with IC50s: 38.2 nM (FLT3) and 144.1 nM (ITD), and fights acute myeloid leukemia.</p>

<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>

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.

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

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>FAK-IN-3 inhibits FAK, reduces PA-1 cell migration/invasion, and tumor growth, with no major side effects.</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>

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

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

Sacibertinib inhibits Trk, targeting EGFR-TK (EC50 110 nM) & HER2 (EC50 244 nM), with anticancer properties.

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

TQ-3959 is an orally active BTKPROTAC degrader, with a DC50 of 14.6 nM. It exhibits antiproliferative activity against both wild-type BTK and BTK C481S mutant cell lines. TQ-3959 demonstrates tumor growth inhibition in female NOD-SCID mice with TMD-8 xenografts. This compound is applicable in the study of B-cell malignancies, such as lymphoma.

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.

<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>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>

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

<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>

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>

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.

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

<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>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>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>

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

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>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>

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

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

Si306, an Src inhibitor, exhibits antitumor activity by reducing the phosphorylation of focal adhesion kinase (FAK) and the expression of epidermal growth factor receptor (EGFR), thereby inhibiting the invasion of human glioblastoma (GBM).

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

FGFR-IN-6 (Compound 5) is an FGFR inhibitor.

JP-153 is an inhibitor of Src-FAK-Paxillin signaling. It suppresses Src-dependent phosphorylation of paxillin (Y118) and subsequent activation of Akt (S473). JP-153 reduces VEGF-induced migration and proliferation of retinal endothelial cells and is applicable in the study of neovascular eye diseases.

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

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

Antiallergic agent-1, an Src family kinase inhibitor, is a new and valuable lead compound with potential as an anti-allergic agent.

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.

TTT 3002: oral FLT3 inhibitor for AML research, blocks D835 mutations, potent at 0.2 nM IC50.

JAK2 JH2 binder-1: potent, selective, Ki=37.1 nM, potential for studying myeloproliferative neoplasms.

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

FAK inhibitor7, a potent FAK inhibitor, demonstrates an IC50 of 3.58 nM. This compound effectively inhibits downstream signaling cascades of FAK (such as Src and AKT), which leads to cell cycle arrest at the G0/G1 phase and induces cytotoxic autophagy in ovarian cancer cells. Additionally, FAK inhibitor7 has been shown to suppress tumor metastasis and growth in ovarian cancer mouse models.

EGFR-IN-18 strongly inhibits L858R/T790M/C797S mutant EGFR (4.9 nM) and also targets wild-type EGFR (47 nM).

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).

ALK ligand-Linker Conjugate 1 is an ALK ligand-connector conjugate used for the synthesis of PROTACALK degrader-4.

EGFR-IN-62: IC50 of 10-242 nM for various EGFR mutations, blocks A549/H1975 cell cycle, induces apoptosis, and inhibits cell motility and proliferation.

PF-06463922 acetate: ALK/ROS1 inhibitor, brain- penetrable, active vs crizotinib-resistant mutants, in NSCLC trials.

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

EGFR-IN-139 (compound PD 18) is an EGFR inhibitor with IC50 values of 12.88 nM (wild type), 10.84 nM (L858R/T790M), and 42.68 nM (L858R/T790M/C797S). It demonstrates significant anticancer activity against the A549 and H1975 cancer cell lines, which express high levels of EGFR. EGFR-IN-139 exhibits strong selectivity for cancer cells and can be utilized in research on non-small cell lung cancer (NSCLC).

FGFR1 inhibitor-6, IC50: 16.31 nM, blocks cell cycle at pro-G1/G2/M and induces apoptosis.

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.

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

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.

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

<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>

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

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

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

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

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

D-69491 hydrochloride is an inhibitor of HER-2 tyrosine kinase activity, blocking the phosphorylation of HER-2 and inhibiting the proliferation of SKOV-3 cells. It exhibits antitumor activity.

<p>FLT3-IN-13 inhibits topoisomerase II/FLT3 in leukemia with IC50 of 2.26 μM, causes G2/M arrest, and promotes apoptosis.</p>

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

(S)-3-Hydroxy Midostaurin is a potent inhibitor of kinases(IC50 of <400 nM for 13 kinases (VEGFR-2, TRK-A, FLT3, et)).

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

BMS-986143: oral BTK inhibitor, IC50=0.26 nM, potential for autoimmune research, also targets TEC, BLK, BMX, TXK, YES1, ITK.

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

VEGFR-2-IN-10 has enhanced antiangiogenic potency against VEGFR2 phosphorylation induced by VEGF with an IC50 value of 0.7 μM and no cytotoxic effects.

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

7PPD-Q is a substituted p-phenylenediamine antioxidant derivative. It exhibits toxicity towards the bacterium V. fischeri (EC50= 14.9 mg/L).

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

Pred17 is an effective EGFR inhibitor with potential applications in lung cancer research.

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

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

JAK3/BTK-IN-3: strong dual JAK3/BTK suppressor, promising for autoimmune disease research.

FAK-IN-21 (compound 9) is a FAK inhibitor with an IC50 value of 37.52 nM. It inhibits cell growth and the phosphorylation of FAK, making it useful for research into diffuse gastric cancer.

Tyk2-IN-3 is an inhibitor of Tyk2 pseudokinase (IC50: 485 nM).

(-)-Cevimeline HCl hemihydrate, a muscarinic agonist, treats Sjogren's xerostomia. Quick absorption, species-dependent metabolism.

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

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.

EGFR-IN-130 (compound 14b) is an EGFR inhibitor and an inducer of apoptosis (apoptoosis). It effectively kills HeLa cancer cells by inducing apoptosis.

Tarloxotinib bromide (TH-4000) is an irreversible inhibitor of EGFR/HER2.

BTK-IN-38 (Example 125) is an efficacious inhibitor of BTK. It effectively suppresses the proliferation of DOHH2 and BT474 cells, with IC50 values of 114 nM and 340 nM, respectively.

BTK-IN-34 (compound 9h) functions as a selective BTK inhibitor, exhibiting antiproliferative effects in RAMOS cells by specifically targeting pBTK (Tyr223) while sparing upstream proteins such as Lyn and Syk in the BCR signaling pathway [1].

VEGFR2-IN-1 is a VEGFR2 inhibitor with antitumor activity used in the study of breast cancer.

BTK-IN-32 (compound C2) acts as a potent BTK inhibitor. Unlike isolated kinase domains, this compound activates full-length BTK as well as its smaller multidomain fragments [1].

EGFR-IN-133 (Compound 24) serves as an inhibitor targeting various mutations of the EGFR, including the wild type, L858R/T790M, d19/T790M, L858R/T790M/C797S, and d19/T790M/C797S with respective IC50 values of 0.1, 0.044, 0.036, 0.04, and 0.054 nM. The compound exhibits favorable pharmacokinetic properties and high oral bioavailability.

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

(Rac)-PT2399 is a potent and specific inhibitor of hypoxia-inducible factor 2a (HIF-2α)(IC50 of 0.01 μM).

HDHD4-IN-1 (compound 3) is an inhibitor of N-acetylneuraminate-9-phosphate phosphatase (HDHD4) with an IC50 value of 11 μM. It is utilized in the research of neurological disorders.

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>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>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>

SJ1008066 is a MAGE-A11 inhibitor with an IC50 of 0.13 μM. It binds to the MAGE homology domain (MHD) and disrupts the MAGE-A11:PCF11 interaction.

MK-8457 is a dual inhibitor of SYK and ZAP70, valuable for rheumatoid arthritis research [1].

CDDD11-8 is an orally administered, highly potent and selective CDK9 and FLT3-ITD inhibitor, with K i values of 8 nM and 13 nM, respectively. It effectively reduces the proliferation of leukemia cell lines, showing particular efficacy against those with the FLT3-ITD mutation [1] [2].