stat5 inhibitor

STAT5-IN-1 (STAT5 Inhibitor) is a cell-permeable inhibitor which suppresses Stat5 via binding to the SH2 domain.

Fedratinib (TG-101348) (TG101348) is an ATP-competitive inhibitor of JAK2 (IC50: 3 nM) with significantly less potent activity against JAK3.

Abrocitinib (PF-04965842) (PF-04965842) is a potent, specific and orally-active JAK1 inhibitor (IC50s: 29 803 nM for JAK1 2).

JAK3i is a selective covalent inhibitor of JAK3 kinase. JAK3i reveals two distinct temporal waves of STAT5 phosphorylation and more potently targets the second wave, which is required for cell cycle progression and T cell proliferation.

HODHBt is a STAT5-SUMO protein-protein interaction inhibitor.

Nifuroxazide (Diarlidan) is an orally available and cell-permeable nitrofuran-based antidiarrheal agent. It has the inhibitory effect against the activation of cellular STAT1 3 5 transcription.

Cenisertib is A potent ATP-competitive multi-kinase inhibitor, showing inhibitory effects on the activity of Aurora-kinase-A B, ABL1, AKT, STAT5, FLT3, as well as kinase inhibitors of FER and its homolog. Cenisertib inhibits the growth of tumor mast cells (MCS) by inhibiting the activity of several different molecular targets. Cenisertib also inhibits tumor growth in pancreatic, breast, colon, ovarian and lung cancer and leukemia in xenograft models.

BD750 is an effective immunosuppressant and a JAK3 STAT5 inhibitor, inhibits IL-2-induced JAK3 STAT5-dependent T cell proliferation(IC50 of 1.5 μM and 1.1 μM in mouse and human T cells, respectively)

HM43239 is an orally active and selective FLT3 inhibitor with IC 50 s of 1.1 nM, 1.8 nM and 1.0 nM for FLT3 WT, FLT3 internal tandem duplication (ITD) and FLT3 D835Y kinases, respectively. HM43239 directly inhibits the kinase activity of FLT3 as a reversible Type I inhibitor and effectively modulates downstream p-STAT5 and p-ERK. HM43239 also demonstrated inhibition of SYK, JAK1 2 and TAK1. HM43239 inhibits the proliferation and induces the apoptosis of leukemic cells [1] [2] [3].

WP1066 is a inhibitor of JAK2 (IC50: 2.30 μM) and STAT3 (IC50: 2.43 μM) in HEL cells; shows activity to JAK2, STAT3 5, and ERK1 2, not JAK1 and JAK3. WP1066 has been used in trials studying the treatment of Melanoma, Brain Cancer, Solid Tumors, and Central Nervous System Neoplasms.

Cryptotanshinone (Cryptotanshinon), a STAT3 inhibitor (IC50: 4.6 μM) in a cell-free assay, strongly inhibits phosphorylation of STAT3 Tyr705, with a little effect on STAT3 Ser727, but no inhibition for STAT1 nor STAT5.

STAT5-IN-2 is an inhibitor of STAT5 with antileukemic effects (EC50s: 9 μM and 5 μM in K562 and KU812 cells, respectively).

CAY10763 is a dual inhibitor of indolamine 2,3-dioxygenase 1 (IDO1; IC50= 46 nM) and STAT3 activation.1It binds to STAT3 (Kd= 530 nM) and selectively reduces the levels of STAT3 phosphorylated at the tyrosine in position 705 (STAT3Y705) over phosphorylated STAT3S727, STAT1, and STAT5 in SKOV3 cells when used at a concentration of 500 nM. It also inhibits STAT3 nuclear translocation in SKOV3 cells. CAY10763 is cytotoxic to HCT116, SKOV3, A549, and HepG2 cancer cells (IC50s = 37, 28, 33, and 12 nM, respectively). It reduces tumor growth in B16/F10 mouse melanoma and HepG2 mouse xenograft models when administered at doses of 100 and 10 mg/kg, respectively. 1.Huang, R., Jing, X., Huang, X., et al.Bifunctional naphthoquinone aromatic amide-oxime derivatives exert combined immunotherapeutic and antitumor effects through simultaneous targeting of indoleamine-2,3-dioxygenase and signal transducer and activator of transcription 3J. Med. Chem.63(4)1544-1563(2020)

CDK8-IN-13 is a CDK8 inhibitor (IC50: 51.9 nM) with potent, selective and oral activity. CDK8-IN-13 induces apoptosis and reduces the expression of p-STAT1 S727 and p-STAT5 S726. CDK8-IN-13 exhibits anti-tumour activity.

BP-1-108 is a potent and selective STAT5 inhibitor.

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.

NS-3-008 hydrochloride (NS-3-008 HCl) is a transcriptional G0 G1 switch 2 (G0s2) inhibitor( IC50 of 2.25 μM).

BVB808 (NVP_BVB808) is a selective inhibitor of JAK2, exhibiting approximately 10 times greater selectivity for JAK2 compared to other members of the JAK family (such as JAK1, JAK3, or TYK2) in vitro. By inhibiting the activation of JAK2, BVB808 reduces the phosphorylation of STAT5, thereby blocking the cell proliferation and survival signaling pathways that depend on JAK2. This compound is utilized in cancer research.

MS-1020 is a JAK3 and STAT3 inhibitor. MS-1020 selectively blocks constitutively-active JAK3 and consistently suppressed interleukin-2-induced JAK3/STAT5 signalling. MS-1020 potently inhibits persistently-active STAT3 in a cell type-specific manner.

SH-4-54 is a most potent, small molecule, nonphosphorylated STAT3 inhibitor.

Compound A8, known as JAK2-IN-9, is a selective JAK2 inhibitor with an IC50 of 5 nM. It effectively inhibits the phosphorylation of JAK2, STAT3, and STAT5, possesses metabolic stabilities, and induces apoptosis. This compound is utilized in the study of myeloproliferative neoplasms (MPNs) [1].

Debio 0617B is a multi-kinase inhibitor that reduces maintenance and self-renewal of primary human AML CD34+ stem progenitor cells. debio 0617B targets key kinases upstream of STAT3 STAT5 signalling, such as JAK, ABL, SRC and class III V receptor tyrosine kinases. debio 0617B can be used to study STAT3 driven solid tumours.

XL019 is a potent and selective JAK2 inhibitor with IC50 of 2.2 nM, 100 fold selectivity over JAK1.

Tyk2-IN-22 (Compound A8) is a selective inhibitor of tyrosine kinase 2 (Tyk2), effectively inhibiting Tyk2, JAK1, and JAK3 with IC50 values of 9.7 nM, 148.6 nM, and 883.3 nM, respectively. Additionally, Tyk2-IN-22 suppresses downstream STAT5 phosphorylation.