JAK/Stat

AST-6 is a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, inhibits tumor growth both in vitro and in vivo

Chrysophanic acid (Chrysophanol) blocks proliferation of colon cancer cells by inhibiting EGFR/mTOR pathway.

Cryptotanshinone, a natural compound isolated from the roots of Salvia miltiorrhiza Bunge (Danshen), dramatically blocks STAT3 Tyr705 phosphorylation but not STAT3 Ser727 phosphorylation in DU145 cells, and significantly inhibits JAK2 phosphorylation with IC50 of ~5 μM without affecting the phosphorylation of upstream kinases c-Src and EGFR.

CUDC-101 is a novel compound which inhibits multiple targets, which is designed to inhibit HDAC, EGFR and Her2.

Curcumol induces apoptosis via caspases-independent mitochondrial pathway in human lung adenocarcinoma ASTC-a-1 cells.

Daphnetin is a coumarin analog that acts as an inhibitor of several protein kinases. It inhibits EGFR kinase (IC50 = 7.67 μM), PKA (IC50 = 9.33 μM), and PKC (IC50 = 25 μM), in vitro. The inhibition of EGFR kinase by daphnetin was competitive to ATP and non-competitive to the peptide substrate. Also acts as a potent antioxidant and anti-malarial agent.

Fludarabine or fludarabine phosphate (Fludara) is a chemotherapy drug used in the treatment of hematological malignancies (cancers of blood cells such as leukemias and lymphomas) .Fludarabine inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase. It is active against both dividing and resting cells.

Genistein, a soy isoflavone, is a multiple tyrosine kinases (e.g., EGFR) inhibitor which acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis.

Lapatinib is a dual tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway.

LY2784544 is identified as being highly selective for JAK2-V617F and has advanced into human clinical trials for the treatment of several myeloproliferative disorders.

Mubritinib (TAK 165) is a potent EGFR and p34cdc2 inhibitor with IC50 of 6 nM and 0.2 μM, respectively. Mubritinib(TAK 165) also inhibits p33cdk2 and p33cdk5.

PD153035 is an extremely potent and specific inhibitor of the tyrosine kinase activity of EGFR.

WZ3146 is an inhibitor of EGFR receptor kinase mutants carrying a mutation in an active site gatekeeper residue (T790M) and is much less potent against wild-type EGFR kinase.

WZ4002 is EGFR inhibitor against EGFR T790M (mutation of the gatekeeper T790 residue) which is detected in 50% of clinically resistant patients to gefitinib or erlotinib.

WZ8040 is a novel EGFR inhibitors that suppress the growth of EGFR-T790M-containing cell lines and inhibit EGFR phosphorylation.

ARRY-380 is an ErbB-2 inhibitor that selectively binds to and inhibits the phosphorylation of ErbB-2, resulting in growth inhibition and death of ErbB-2-expressing tumor cells.

XL647 is an orally bioavailable small-molecule RTK inhibitor that binds to and inhibits several tyrosine receptor kinases that play major roles in tumor cell proliferation and tumor vascularization, including EGFR, HER2, ERBB2, VEGFR and EphB4.

TG-101348 is an orally bioavailable, ATP-competitive and selective inhibitor of Janus-associated kinase 2 with potential antineoplastic activity.

Colivelin TFA is a brain penetrant neuroprotective peptide and a potent activator of STAT3, suppresses neuronal death by activating STAT3 in vitro. Colivelin TFA exhibits long-term beneficial effects against neurotoxicity, Aβ deposition, neuronal apoptosis, and synaptic plasticity deficits in neurodegenerative disease. Colivelin TFA has the potential for the treatment of alzheimer's disease and ischemic brain injury.

Colivelin is a brain penetrant neuroprotective peptide and a potent activator of STAT3, suppresses neuronal death by activating STAT3 in vitro. Colivelin exhibits long-term beneficial effects against neurotoxicity, Aβ deposition, neuronal apoptosis, and synaptic plasticity deficits in neurodegenerative disease. Colivelin has the potential for the treatment of alzheimer's disease and ischemic brain injury

SU-4313 is a small-molecule modulator of protein tyrosine kinases (PTKs). It inhibits multiple receptor tyrosine kinases with reported IC₅₀ values of 14.5 μM (PDGFR), 18.8 μM (FLK-1/VEGFR2), 11 μM (EGFR), 16.9 μM (HER2 kinase), and 8.0 μM (IGF-1R).

Through its multi-kinase inhibitory profile, SU-4313 modulates tyrosine kinase–mediated signal transduction pathways involved in the regulation of cell proliferation and growth. It is therefore commonly used as a research tool for investigating aberrant receptor tyrosine kinase signaling and proliferation-associated pathways.

AK-2292 is a potent and selective degrader of the STAT5 transcription factor, exhibiting a DC50 of 0.10 μM. This compound effectively induces the degradation of STAT5A/B proteins both in vitro and in vivo, demonstrating potential for tumor regression in acute myeloid leukemia and chronic myeloid leukemia xenograft mouse models. Additionally, AK-2292 features an alkyne group, enabling it to participate in copper-catalyzed azide-alkyne cycloaddition (CuAAc) reactions with azide-containing molecules, making it a valuable tool for chemical biology applications.

SJ10542 is a potent and selective PROTAC degrader targeting JAK2 and JAK3. With DC50 values of 14 nM for JAK2 and 11 nM for JAK3 in patient-derived xenograft cells (PDX), SJ10542 demonstrates significant antitumor activity. This compound is valuable for research in hematological malignancies and autoimmune diseases, facilitating the exploration of targeted degradation mechanisms in these therapeutic areas.

SJ988497 is a potent PROTAC JAK2 degrader that targets JAK2 for degradation, playing a critical role in the inhibition of CRLF2-rearranged (CRLF2r) cell proliferation. Functionally, SJ988497 induces degradation of the neosubstrate GSPT1 through its architecture consisting of a Ruxolitinib derivative, a linker, and the CRBN ligand Pomalidomide. This compound is particularly valuable for research focused on acute lymphoblastic leukemia (ALL).

PROTAC JAK1 Degrader 1 is a selective PROTAC agent targeting JAK1, exhibiting a DC50 of 214 nM. This compound initiates rapid degradation of JAK1, leading to significant antitumor activity. It serves as a valuable tool for investigating JAK1-related signaling pathways and developing therapeutic strategies for malignancies driven by JAK1 dysregulation.

MS154 is a novel E3 ligase cereblon-recruited degrader specifically targeting epidermal growth factor receptor (EGFR). It has demonstrated potent degradation of the EGFR L858R mutant in cancer cell lines with Kd values of 1.8 nM and 3.8 nM for wild-type and mutant EGFR, respectively. This selective degradation mechanism highlights its potential as an anticancer agent, particularly in lung cancer treatment. MS154 operates through an E3 ligase-dependent pathway, representing a promising therapeutic strategy for treating EGFR-driven malignancies.

PROTAC TYK2 degradation agent1 is a selective degrader targeting TYK2, effectively facilitating its degradation with a DC50 value of 14 nM. This compound highlights significant biological activity in modulating TYK2 levels, making it a useful tool for investigating autoimmune diseases. Research applications include studying the role of TYK2 in inflammatory pathways and evaluating potential therapeutic strategies.

Triacetylresveratrol is an acetylated analog of Resveratrol that functions as an inhibitor of STAT3 and NF-κB signaling pathways. It effectively reduces the phosphorylation levels of STAT3 and NF-κB in a dose- and time-dependent manner in PANC-1 and BxPC-3 cancer cell lines. Its promising anticancer activity makes it a valuable tool for research in cancer biology and therapeutic development.

Niclosamide (BAY2353) is an orally active antihelminthic agent used in parasitic infection research. Niclosamide is a STAT3 inhibitor with an IC50 of 0.25 μM in HeLa cells. Niclosamide has biological activities against cancer, inhibits DNA replication in Vero E6 cells.

Osunprotafib (ABBV-CLS-484) is an orally active and selective active site PTPN1 (IC50: 2.5 nM) and PTPN2(IC50: 1.8 nM) inhibitor. Osunprotafib has 6-8-fold weaker activity on PTPN9 and no detectable activity on SHP-1 or SHP-2. Osunprotafib increases the sensitivity of human cancer cell lines to IFNγ. Osunprotafib generates robust anti-tumor immunity by enhancing JAK-STAT signalling and reducing T cell dysfunction.

Cucurbitacin IIa is a potent EGFR inhibitor with an IC50 of 1.455 nM, demonstrating effective modulation of the EGFR signaling pathway. This compound induces caspase-3-dependent apoptosis, downregulates survivin expression, and enhances autophagy, while disrupting the actin cytoskeleton and arresting the cell cycle at the G2/M phase. Additionally, Cucurbitacin IIa exhibits anti-inflammatory properties, making it a valuable tool for research into inflammation-related diseases, depression, and various cancers, including non-small cell lung cancer.

Pentadecanoic acid is a saturated fatty acid that serves as an inhibitor of STAT3, a critical transcription factor involved in cellular signaling pathways. Its primary biological activity includes modulation of inflammatory responses and potential anti-cancer effects. This compound is utilized in research applications focused on cancer therapy, inflammation studies, and metabolic regulation.

STAT3-IN-13 is a potent inhibitor of the STAT3 signaling pathway, specifically targeting the SH2 domain with a binding affinity of 0.46 μM. This compound effectively inhibits the phosphorylation of STAT3 at Y705, subsequently reducing the expression of downstream target genes. In vitro studies demonstrate its ability to induce apoptosis, while in vivo applications show suppression of tumor growth and metastasis. STAT3-IN-13 is a valuable tool for cancer research, particularly in studies focused on the modulation of aberrant STAT3 activity.

Atiprimod hydrochloride is a potent inhibitor of the signal transducer and activator of transcription 3 (STAT3). It demonstrates significant antitumor, anti-inflammatory, and anti-angiogenic properties by blocking IL-6 and VEGF signaling pathways, inhibiting the phosphorylation of JAK2 and JAK3. Atiprimod effectively induces cell cycle arrest, autophagy, and apoptosis in various cancer cell types, particularly through the activation of the PERK/eIF2α/ATF4/CHOP pathway in breast cancer cells. Its efficacy in tumor xenograft mouse models underscores its potential for investigating therapeutic approaches in conditions such as pituitary adenoma, breast cancer, multiple myeloma, and acute myeloid leukemia (AML).

JP-11646 is a potent pan-PIM inhibitor specifically targeting PIM2 with an IC50 of 0.5 nM. This reversible, ATP non-competitive inhibitor significantly reduces the mRNA levels of PIM1, PIM2, and PIM3. JP-11646 has demonstrated efficacy in inhibiting cell viability in small cell lung cancer (SCLC) and large cell neuroendocrine carcinomas of the lung (LCNEC), leading to apoptosis or necroptosis through decreased p-4EBP-1 and altered caspase activity. This reagent is valuable for research applications in SCLC, LCNEC, acute myeloid leukemia (AML), multiple myeloma (MM), and triple-negative breast cancer (TNBC).

Pim-1 kinase inhibitor 10 is a selective inhibitor of PIM-1 and PIM-2 kinases, functioning through both competitive and non-competitive mechanisms. This compound effectively induces apoptosis in cancer cells, demonstrating significant anticancer activity. Additionally, Pim-1 kinase inhibitor 10 activates caspase 3 and 7, further contributing to its potential as a therapeutic agent in cancer research.

Atiprimod dimaleate is a selective inhibitor of the transcription factor STAT3, demonstrating significant antitumor, anti-inflammatory, and anti-angiogenic properties. By disrupting IL-6 and VEGF signaling pathways, it inhibits the phosphorylation of JAK2 and JAK3, effectively blocking the JAK-STAT signaling cascade. Atiprimod dimaleate induces cell cycle arrest, promotes autophagy and apoptosis, and activates the PERK/eIF2α/ATF4/CHOP pathway to trigger ER stress-mediated apoptosis in cancer cells. This reagent is valuable for research related to breast cancer, pituitary adenoma, multiple myeloma, and acute myeloid leukemia (AML), and has shown promising anti-tumor activity in xenograft mouse models.

WP-1034 is a selective JAK-STAT inhibitor that exhibits pro-apoptotic and antileukemic properties, particularly in acute myeloid leukemia (AML) models. By blocking the activation of Stat 3 and Stat 5, WP-1034 effectively induces cell cycle arrest and triggers apoptosis in affected cells. This reagent is valuable for research focused on understanding the mechanisms and therapeutic avenues in AML.

EGFR-IN-47 is a potent orally active inhibitor of the EGFR L858R/T790M/C797S mutations, with an IC50 of 0.01 μM. This compound effectively induces cell cycle arrest and promotes apoptosis in cancer cells. EGFR-IN-47 holds significant potential for research applications related to non-small cell lung cancer (NSCLC).

Dehydrocrenatidine is a natural alkaloid that functions as a selective inhibitor of Janus kinases (JAK). This compound exhibits significant biological activity by inhibiting voltage-gated sodium channels, which may alleviate mechanical allodynia in neuropathic pain models. Dehydrocrenatidine serves as a valuable tool for research in pain mechanisms and the therapeutic targeting of JAK pathways.

EGFR-IN-78 is a reversible inhibitor of the EGFR variant C797S-TK, classified as a 2-aminopyrimidine derivative. This compound induces apoptosis and exhibits significant anti-proliferative activity by inhibiting EGFR phosphorylation. Additionally, EGFR-IN-78 effectively arrests the cell cycle at the G2/M phase, making it a valuable tool for research applications focused on targeted cancer therapies.

HDAC/JAK/BRD4-IN-1 is a potent inhibitor targeting histone deacetylases (HDAC), Janus kinases (JAK), and bromodomain-containing protein 4 (BRD4). This compound demonstrates significant anti-proliferative effects and promotes apoptosis in MDA-MB-231 breast cancer cells. Additionally, HDAC/JAK/BRD4-IN-1 exhibits promising anticancer activity in vivo, making it a valuable tool for research in cancer therapeutics and the study of epigenetic and signaling pathways.

EGFR-TK-IN-4 is a potent and selective inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK). It has been demonstrated to induce apoptosis in cancer cells and exhibits significant antitumor activity. This compound is suitable for studying EGFR signaling pathways and developing targeted therapies in oncology research.

YS-363 is a potent and selective orally active inhibitor of the epidermal growth factor receptor (EGFR), exhibiting IC50 values of 0.96 nM for wild-type and 0.67 nM for the L858R mutant form. This compound effectively induces G0/G1 cell cycle arrest and promotes apoptosis in target cells. YS-363 is valuable for research applications focused on cancer therapeutics and the molecular mechanisms of EGFR signaling.

LY5 is a potent inhibitor of STAT3, exhibiting an IC50 of 0.5 μM. It induces apoptosis and effectively inhibits STAT3 phosphorylation, demonstrating significant antitumor activity in vivo. This compound is utilized in cancer research to explore the mechanisms of STAT3-related signaling pathways and their implications in tumorigenesis.

Pim-1 kinase inhibitor 8 is a selective inhibitor of the PIM-1 kinase, exhibiting an IC50 value of 14.3 nM. This compound effectively disrupts cellular proliferation and migration by inhibiting PIM-1, leading to the induction of apoptosis and autophagy. In vivo studies demonstrate its capability to inhibit solid tumor growth in Solid Ehrlich Carcinoma (SEC)-bearing mice. Pim-1 kinase inhibitor 8 is valuable for research focused on breast and liver cancer.

HJC0123 is a potent STAT3 inhibitor that effectively suppresses the proliferation of hepatic stellate cells while inducing cell cycle arrest and apoptosis. It reduces STAT3 phosphorylation, nuclear translocation, and transcriptional activity, leading to increased IL-6 production and inhibition of Smad2/3 phosphorylation, along with down-regulation of SOCS3. HJC0123 serves as a valuable tool for investigating liver fibrosis and related pathways.

Os30 is a potent fourth-generation EGFR inhibitor specifically targeting the EGFRC797S-TK mutation. With IC50 values of 18 nM and 113 nM for EGFRDel19/T790M/C797S TK and EGFRL858R/T790M/C797S TK, respectively, Os30 effectively inhibits EGFR phosphorylation, induces G1 phase cell cycle arrest, and triggers apoptosis in KC-0116 (BaF3-EGFRDel19/T790M/C797S) cells. This compound demonstrates significant antitumor activity in non-small cell lung cancer (NSCLC) harboring the EGFRC797S mutation, making it a valuable tool for cancer research and therapeutic exploration.

CDK6/PIM1-IN-1 is a potent dual inhibitor targeting CDK6 and PIM1, with IC50 values of 39 nM and 88 nM, respectively, and an additional inhibition of CDK4 at an IC50 of 3.6 nM. This reagent significantly inhibits the proliferation of acute myeloid leukemia (AML) cells, induces G1 phase cell cycle arrest, and promotes apoptosis. CDK6/PIM1-IN-1 demonstrates strong anti-AML activity, making it a valuable tool for research in cancer biology and therapeutic development.