TGF-beta/Smad Inhibitor

Itacnosertib (TP-0184) is the inhibitor for FLT3, ACVR1 (ALK2, IC₅₀=8 nM) and JAK2 (IC₅₀=8540 nM). Itacnosertib exhibits anti-leukemic activity.

Phyllanthin is an effective oral anticancer agent. Phyllanthin inhibits MOLT-4 cell viability, increases apoptosis, inhibits cell migration and invasion. Phyllanthin exerts anti-fibrotic effects by down-regulating TGF signaling pathway via ALK5 and Smad2/3. Phyllanthin also has anti-inflammatory and antibacterial properties .

3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles is an inhibitor for bone morphogenetic protein 2 (BMP2) with an IC₅₀ of 2.2 μM. 3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles is inhibitor for mitogen-activated protein kinase 1 (MEK1). 3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles exhibits anti-inflammatory and neuroprotective activity in EAE mouse model.

Cibotercept (KER-012) is a novel, modified, investigational activin receptor type IIB (ActRIIB) ligand trap designed to target select TGF-β ligands, including activins A and B, GDFs 8 and 11, to rebalance the defective activin receptor type II signaling observed in PAH.

Pirfenidone-d₅ (AMR69-d₅) is a deuterium labeled Pirfenidone. Pirfenidone is an antifibrotic agent that attenuates CCL2 and CCL12 production in fibrocyte cells. Pirfenidone has growth-inhibitory effect and reduces TGF-β2 protein levels in human glioma cell lines. Pirfenidone also has anti-inflammatory activities.

Disitertide (P144) is a peptidic transforming growth factor-beta 1 (TGF-β1) inhibitor specifically designed to block the interaction with its receptor. Disitertide (P144) is also a PI3K inhibitor and an apoptosis inducer.

Vevorisertib (ARQ 751) is an orally active allosteric AKT inhibitor that blocks AKT phosphorylation. Vevorisertib inhibits tumor cell proliferation through Cyclin D1 and Ki67. Vevorisertib inhibits liver fibrosis through collagen accumulation, alpha-SMA, COL1, and TGF-beta. Vevorisertib reduces total bilirubin. Vevorisertib significantly reduces tumor size in a cirrhotic rat HCC model. Vevorisertib can be used for research on hepatocellular carcinoma.

Kaempferol 3-O-gentiobioside is an orally active flavonoid, with a K_a value of 57 µM against human NOTCH1 and an IC₅₀ value of 50 μM against α-glucosidase. Kaempferol 3-O-gentiobioside inhibits the NOTCH signaling pathway. It downregulates the expression of TLR4 and NLRP3, and suppresses the activation and nuclear translocation of NF-κB. Kaempferol 3-O-gentiobioside inhibits the expression of MUC5AC, reduces nitrite and ROS levels, and attenuates excessive mucus secretion. It exhibits antibacterial activity, reducing the formation and growth of MRSA biofilms. Kaempferol 3-O-gentiobioside blocks the TGF-β/ALK5/Smad signaling pathway and inhibits epithelial-mesenchymal transition. It suppresses the proliferation, migration, invasion and metastatic growth of tumor cells. Kaempferol 3-O-gentiobioside alleviates airway inflammation and mucus hypersecretion in mice with allergic asthma. It reduces the volume of ovarian cancer xenografts in mice. Kaempferol 3-O-gentiobioside can be used in research related to allergic asthma, diabetes, MRSA infection, breast cancer, gastric cancer and ovarian cancer.

Halofuginone lactate (RU-19110 lactate), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a K_i of 18.3 nM. Halofuginone lactate is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity. Halofuginone lactate is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca²⁺ channels. Halofuginone lactate has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects.

TGFβ-IN-2 is an orally active TGF-β inhibitor. TGFβ-IN-2 suppresses the TGF-β-induced protein expression of COL1A1, α-SMA, and p-Smad3 in vitro. TGFβ-IN-2 demonstrates excellent anti-fibrotic efficacy in Bleomycin (HY-108345)-induced pulmonary fibrosis model. TGFβ-IN-2 can be used for the study of pulmonary fibrosis.

Nisevokitug (NIS-793) is a humanized IgG2λ monoclonal antibody and an inhibitor of the TGF-β signaling pathway. Nisevokitug blocks the binding of TGF-β to the membrane-bound TGF-βR1/TGF-βR2 receptors, inhibits both Smad-dependent and Smad-independent downstream cascade signaling, downregulates fibrosis-related genes, and reverses the TGF-β-mediated immunosuppressive microenvironment. Nisevokitug can be used in the research of diseases such as pancreatic ductal adenocarcinoma, colorectal cancer, myelofibrosis, and myelodysplastic syndrome.

Hydrochlorothiazide (Standard) is the analytical standard of Hydrochlorothiazide. This product is intended for research and analytical applications. Hydrochlorothiazide (HCTZ), an orally active diuretic agent of the thiazide class, inhibits transforming TGF-β/Smad signaling pathway. Hydrochlorothiazide has direct vascular relaxant effects via opening of the calcium-activated potassium (KCA) channel. Hydrochlorothiazide improves cardiac function, reduces fibrosis and has antihypertensive effect.

MY-673 is a colchicine binding site inhibitor (CBSI), that inhibits tubulin polymerization. MY-673 inhibits the ERK signaling pathway, which in turn affects SMAD4 protein expression levels in the TGF-β/SMAD pathway. MY-673 inhibited cell proliferation, migration and induced apoptosis in vivo and in vitro.

Myostatin inhibitory peptide 2 (compd 2) is a myostatin inhibitor with a K_d of 35.9 nM. Myostatin inhibitory peptide 2 can be used for researches of muscle atrophic disorders.

Luspatercept (mIgG2a) (RAP-536) is a fusion protein, consisting of a modified extracellular domain of human ActRIIB linked to the murine IgG2a Fc domain. Luspatercept (mIgG2a) inhibits Smad2/3 signaling, promotes differentiation of late-stage erythroid precursors and mitigates ineffective erythropoiesis (IE) in murine β-thalassemia. Luspatercept (mIgG2a) reduces anemia, α-globin aggregates, hemolysis, and disease complications of IE such as iron overload, splenomegaly, and bone defects.

Rilogrotug (AV-380) is a humanized IgG1 monoclonal antibody targeting GDF15.

Psicose (DL-Psicose) is an orally effective sugar substitute. Psicose activates the PI3K/Akt/mTOR pathway to promote muscle synthesis. Psicose upregulates IGF-1 and downregulates Myostatin. Psicose normalizes mitochondrial dysfunction by increasing G6P activity. Psicose enhances the activity of antioxidant enzymes and reduces oxidative stress markers. Psicose increases muscle mass, grip strength and muscle weight in aged mice and diet-induced obese mice. Psicose improves obesity and type 2 diabetes. Psicose can be used in the research of age-related sarcopenia.

Itacnosertib hydrochloride (TP-0184 hydrochloride) is the inhibitor for FLT3, ACVR1 (ALK2, IC₅₀=8 nM) and JAK2 (IC₅₀=8540 nM). Itacnosertib hydrochloride exhibits anti-leukemic activity.

Pentabromophenol (PBP) is a brominated flame retardant (BFR) widely used in various consumer products to reduce the flammability of materials used in different utility items. Pentabromophenol can accelerate the degradation of transforming growth factor-β (TGF-β) receptors by promoting clathrin-mediated endocytosis, thereby inhibiting the TGF-β signaling pathway. Additionally, Pentabromophenol can also induce apoptosis in peripheral blood mononuclear cells (PBMCs).

Hydrochlorothiazid-d₂ is the deuterium labeled Hydrochlorothiazide. Hydrochlorothiazide (HCTZ), an orally active diuretic agent of the thiazide class, inhibits transforming TGF-β/Smad signaling pathway. Hydrochlorothiazide has direct vascular relaxant effects via opening of the calcium-activated potassium (KCA) channel. Hydrochlorothiazide improves cardiac function, reduces fibrosis and has antihypertensive effect.