STAT3 Inhibitor

STAT3-IN-49 (compound B16) is a potent and selective STAT3 inhibitor. STAT3-IN-49 binds to the SH2 domain of STAT3, thereby suppressing its phosphorylation and nuclear translocation. STAT3-IN-49 inhibits triple-negative breast cancer (TNBC) cell migration, invasion, and colony formation. STAT3-IN-49 inhibits tumor growth in an MDA-MB-231 xenograft mouse model. STAT3-IN-49 can be used for TNBC research.

Avicin D is a plant triterpenoid. Avicin D induces Autophagy by activation of AMPK. Avicin D inhibits mTOR and S6 kinase activity. Avicin D selectively induces Apoptosis and downregulates p-STAT-3, bcl-2, and Survivin. Avicin D has properties of being a selective Glucocorticoid receptor modulator. Avicin D inhibits NF-κB activation. Avicin D shows anti-tumor effects against cutaneous T-cell lymphomas.

P-gp-IN-36 is a potent P-glycoprotein (P-gp) inhibitor with an EC₅₀ of approximately 1 μM. P-gp-IN-36 inhibits the efflux function of P-glycoprotein, overcoming P-gp-mediated multidrug resistance in cancer cells. P-gp-IN-36 inhibits STAT3 phosphorylation and reduces total STAT3 expression. P-gp-IN-36 sensitizes P-gp-expressing cancer cells to the cytostatic effects of conventional cytostatic drugs. P-gp-IN-36 can be used for the research of multidrug-resistant cancer.

8α-Tigloyloxyhirsutinolide 13-O-acetate (8αTGH) is a potent and orally active STAT3 inhibitor. 8α-Tigloyloxyhirsutinolide 13-O-acetate induces early oxidative stress and pyroptosis, and late DNA damage, cell cycle arrest, apoptosis in the TNBC cells. 8α-Tigloyloxyhirsutinolide 13-O-acetate suppresses tumor cell growth in vitro and tumor growth in vivo.

(-)-Salcolin B (Tricin 4'-O-(threo-β-guaiacylglyceryl) ether) is an isomer of Salcolin B (HY-N16766) and anti-inflammatory agent. (-)-Salcolin B is isolable from Njavara. (-)-Salcolin B downregulates the activities of NF-κB and STAT3, reduces the expressions of iNOS and COX-2, activates the ERK signaling pathway, and inhibits LPS-induced NO and ROS production. (-)-Salcolin B induces Apoptosis. (-)-Salcolin B inhibits TPA (HY-18739)-induced ear edema. (-)-Salcolin B possesses antioxidant activity. (-)-Salcolin B can be used in research related to inflammatory diseases, colon adenocarcinoma, ovarian cancer and breast cancer.

CPA7 is a novel Stat3 inhibitor. CPA7 downregulates survivin, Bcl-XL, and Mcl-1. CPA7 induces Apoptosis. CPA7 enhances the radiosensitivity of prostate cancer. CPA7 has anti-cancer effects against prostate cancer.

KB-0118 (BBC0115) is an orally active BET bromodomain inhibitor. KB-0118 selective binds to BRD2 and BRD4 over BRD3, with K_d values of 36.7 μM for BRD2 BD1 and 47.4 μM for BRD4 BD1. KB-0118 inhibits pro-inflammatory cytokines, including TNF, IL-1β, and IL-23a and selectively suppresses Th17 cell differentiation. KB-0118 modulates Th17-driven inflammation occurs through epigenetic suppression of BRD4, confirmed by downregulation of STAT3 and BRD4 target genes. KB-0118 has immunomodulatory effects in inflammatory bowel disease (IBD) model.

G721-0282 is an orally active CHI3L1 inhibitor. G721-0282 can reduce the expression of inflammatory proteins and cytokines. G721-0282 inhibits the activation of the NF-κB signaling pathway. G721-0282 inhibits neuroinflammation and reduces anxious behavior. G721-0282 significantly inhibits the proliferation of osteosarcoma (OS) cells by suppressing the STAT3 signaling pathway. G721-0282 induces OS cell apoptosis by upregulating pro-apoptotic protein levels and downregulating anti-apoptotic protein levels. G721-0282 can be used for researches on neuroinflammatory conditions and cancer.

UT-105 is an orally active, selective androgen receptor (AR) degrader. UT-105 binds to the N-terminal domain of AR, inhibits the transactivation of AR, blocks the recruitment of AR to androgen response elements, and induces AR degradation. UT-105 inhibits the JAK-STAT signaling pathway, including reducing the expression of interferon-stimulated genes, inhibiting the phosphorylation of STAT1 and STAT3, and blocking the recruitment of STAT1 to response elements. UT-105 exhibits anticancer activity against AR-positive triple-negative breast cancer (TNBC). UT-105 can be used in the research of selective androgen receptor modulator-resistant ER-positive breast cancer and triple-negative breast cancer.

WR-S-462 is a STAT3 inhibitor. WR-S-462 effectively suppresses STAT3 phosphorylation and biological functions in vitro. WR-S-462 inhibits MDA-MB-231 cells with an IC₅₀ of 0.03 μM. WR-S-462 displays a strong binding affinity towards the STAT3 protein with a K_d of 58 nM. WR-S-462 inhibits the nuclear translocation of p-STAT3, selectively inhibits the expression of p-STAT3^Tyr705 and downstream target genes regulated by STAT3 in MDA-MB-231 cells such as Cyclin D1, Bcl-2, and Bcl-xl. WR-S-462 inhibits TNBC (triple-negative breast cancer) growth and metastasis.

EC-70124 is an orally active multikinase inhibitor targeting IKKβ and JAK2. EC-70124 blocks IkB phosphorylation and STAT3 (Tyr705) activation, suppressing NF-κB nuclear translocation and STAT3 transcriptional activity. EC-70124 reduces tumor growth and cancer stem cell (CSC) populations in prostate cancer cells and xenograft models. EC-70124 is promising for research of prostate cancer.

JAK1/STAT3-IN-1 (compound 4f) is an anti-AD (atopic dermatitis) agent by inhibiting JAK1/STAT3 signaling pathway. JAK1/STAT3-IN-1 inhibits NO generation with an IC₅₀ of 2.17 μM. JAK1/STAT3-IN-1 improves the skin condition of AD-like mice, reduces inflammatory infiltration, inhibits the expressions of p-JAK1/JAK1 and p-STAT3/STAT3, and mitigates the excessive immune response on Calcipotriol (HY-10001) (MC903)-induced AD-like mice.

STAT3-IN-54 is a STAT3 inhibitor. STAT3-IN-54 induces Apoptosis and G0/G1 cell cycle arrest. STAT3-IN-54 exhibits selective anticancer activity against non-small cell lung cancer cells. STAT3-IN-54 can be used for research on non-small cell lung cancer.

Sorafenib-d₃ (Donafenib) tosylate is the deuterated-labeled Sorafenib tosylate (HY-10201A). Sorafenib (Bay 43-9006) tosylate is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib tosylate induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib tosylate inhibits tumor growth and metastasis in mouse and rat models. Sorafenib tosylate can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

CHI3L1-IN-4 (Compound 8) is a Chitinase-3-Like Protein 1 (CHI3L1) inhibitor with a K_d of 6.8  μM. CHI3L1-IN-4 significantly reduces glioblastoma (GBM) spheroids viability and attenuates phospho-STAT3 levels by disrupting CHI3L1 pathway. CHI3L1-IN-4 can be used for GBM research.

JAK1-IN-20 (Compound 38) is a gut-restricted, orally active, selective JAK1 inhibitor with an IC₅₀ of <0.5 nM. JAK1-IN-20 inhibits the enzymatic activity of JAK1, reduces the production of proinflammatory cytokines (TNF-α, IL-6), and suppresses the phosphorylation of STAT3. JAK1-IN-20 ameliorates ulcerative colitis. JAK1-IN-20 can be used for the research of inflammatory bowel disease.

EGFR/Akt/STAT3-IN-1 is an EGFR/Akt/STAT3 inhibitor (IC₅₀ values of 9.79 μM, 17.80 μM, and 8.30 μM, respectively) that induces apoptosis and G0/G1 cell cycle arrest by inhibiting EGFR tyrosine kinase, Akt kinase, and STAT3 transcriptional activity, and exhibits selective cytotoxicity against cancer cells. EGFR/Akt/STAT3-IN-1 can be used for research on non-small cell lung cancer.

GL-4512 is an orally active LILRB4/ILT3 inhibitor with an IC₅₀ of 37 nM against human targets, and human K_d values of 18.1 nM and 39.2 nM, respectively. GL-4512 directly binds to the extracellular pockets of LILRB4/ILT3 that accommodate their ligands, blocks the LILRB4-SCG2 signaling pathway, and inhibits the downstream SHP1/SHP2 and STAT3 signaling pathways. GL-4512 restores anti-tumor immune activity, promotes the production of IFN-γ and IL-2, enhances the activation of cytotoxic T cells, reduces tumor cell viability, inhibits tumor growth, and strengthens intratumoral immune activation. GL-4512 can be used in research related to colorectal cancer and acute myeloid leukemia.

YN11 is a STAT3 inhibitor (K_d=11.9 μM). YN11 directly binds to the SH2 domain of STAT3, inhibits the phosphorylation of STAT3, and reduces the expression of downstream target proteins. YN11 induces cell cycle arrest, promotes apoptosis, and inhibits cell invasion and migration in prostate cancer cells. YN11 suppresses tumor growth in a prostate cancer xenograft mouse model. YN11 does not cause significant body weight loss or obvious histopathological changes in major organs in xenograft mice. YN11 is applicable to relevant research on prostate cancer.

WP1193 is a novel JAK2/STAT3 pathway inhibitor. WP1193 suppresses phosphorylation of JAK2 and STAT3. WP1193 decreases expression of stem cell markers including CD133 and c-myc. WP1193 can be used in the research of glioblastoma.