fibrotic diseases

Ogerin is a selective GPR68 positive allosteric modulator (pEC50: 6.83) that blocks recall in fear conditioning in mice. It exhibits inverse agonist and antagonist activity (Ki, 220 nM) at the A2A receptor and weak antagonist activity (Ki, 736 nM) at the 5-HT2B receptor.

HA 155 (Autotaxin Inhibitor IV) is a boronic acid-based compound, inhibiting ATX with IC50 of 5.7 nM by selectively binding to its catalytic threonine.

AZD-8055 is an orally bioavailable, highly selective, ATP-competitive mTOR kinase inhibitor that directly binds to the ATP-binding pocket of the mTOR kinase domain, while potently inhibiting both mTORC1 and mTORC2 complexes (IC₅₀ values of 0.8 nM and 0.1 nM, respectively). AZD-8055 is suitable for research in oncology, metabolic diseases, and fibrotic disorders.

GPR84 antagonist 8 is a selective GPR84 antagonist applicable for investigating inflammatory and fibrotic diseases.

PAT-1251 is an inhibitor of LOXL2 with IC50s of 10, 0.12, and 0.16 μM for the mouse, rat, and dog and can be used in studies about fibrotic diseases.

Lenumlostat is an orally available, selective and potent lysyl oxidase-like protein 2 (LOXL2) inhibitor with inhibitory effects on hLOXL2, hLOXL3 and LOXL2 for the study of fibrotic diseases.

SR-302 is a potent and selective inhibitor of DDR/p38, with IC50 values of 0.125 μM for p38α, 0.023 μM for DDR1, and 0.018 μM for DDR2. It is utilized in research related to fibrotic diseases, such as kidney and lung fibrosis, atherosclerosis, and various types of cancer.

5-HT2B antagonist-2 (Compound 19c) is a 5HT2B receptor antagonist with an IC50 of 1.09 nM. It effectively downregulates the expression of fibrosis-related genes α-SMA, Timp1, Col1a1, and Col3a1, significantly reducing cellulose deposition. In a CCl4-induced liver fibrosis mouse model, it decreases the fibrotic area and inhibits the progression of fibrosis. This compound is useful for research into immune-inflammatory related diseases, particularly pulmonary fibrosis.

Galectin-3-IN-6 (Compound 12) is an orally active galectin-3 (Gal-3) inhibitor, with an IC50 of 12 nM and a Kd of 13 nM for Gal-3. In a CCl4-induced mouse model of acute liver injury and fibrosis, Galectin-3-IN-6 significantly reduces fibrosis markers collagen-1 and α-smooth muscle actin (αSMA) by 64% and 71%, respectively, demonstrating notable anti-fibrotic activity. Galectin-3-IN-6 is applicable for research in fibrosis-related diseases, cancer, and cardiovascular disorders.

HDAC6-IN-53 (Compound W28) is an inhibitor targeting histone deacetylase 6 (HDAC6) with an IC50 of 19.65 nM. It reduces the idiopathic pulmonary fibrosis (IPF) phenotype by inhibiting TGF-β1-induced collagen expression and demonstrates therapeutic efficacy in a bleomycin-induced mouse model of pulmonary fibrosis. HDAC6-IN-53 is applicable for research in idiopathic pulmonary fibrosis and related pulmonary fibrotic diseases.

BRD4-IN-10 (Compound 31) is a selective BRD4 inhibitor with an IC50 of 13.5 nM. It exhibits anti-inflammatory and anti-fibrotic effects, possesses good metabolic stability, favorable pharmacokinetic properties, and safety. BRD4-IN-10 is suitable for research in kidney fibrosis diseases.

JNK2/3-IN-1 (Compound 56d) is an irreversible covalent inhibitor of c-Jun N-terminal kinases 2/3 (JNK2/3), with IC50 values of 830 nM and 1909 nM, respectively. JNK2/3-IN-1 is potentially useful for research in neurodegenerative diseases such as Parkinson's and Alzheimer's, as well as fibrotic diseases.

ALK5-IN-85 (Compound 19) is an inhibitor of TGFβRI (ALK5) with an IC50 of less than 100 nM. It can be used for the treatment of respiratory diseases such as idiopathic pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, and lung cancer, as well as for research on skin and ocular fibrotic diseases.

THR-β agonist 11 is an orally active and selective thyroid hormone receptor (THR-β) agonist. It demonstrates robust cholesterol-lowering effects in cholesterol-fed rats. In a high-fat diet-carbon tetrachloride (HFD-CCl4) induced model of metabolic dysfunction-associated steatohepatitis (MASH) in mice, THR-β agonist 11 significantly reduces serum total triglycerides (TG), low-density lipoprotein cholesterol (LDL-cholesterol), liver total cholesterol (TC), and TG levels. Additionally, it alleviates hepatic steatosis, inflammation, and fibrosis. THR-β agonist 11 is applicable in the study of MASH and other fibrotic diseases.

LIFR/GPBAR1 modulator 1 is an orally active, potent GPBAR1 agonist (EC50= 0.2 μM) and LIFR inhibitor (IC50= 7.9 μM). It enhances the expression of leukemia inhibitory factor (LIF)-mediated LIFR and GPBAR1 mRNA, while significantly reducing the expression of fibrosis markers (COL1A1, ASMA, and TGFβ), decreasing TIMP1 levels, and increasing MMP9 expression. LIFR/GPBAR1 modulator 1 is applicable for research into human fibrotic diseases.

ROCK2-IN-12 (Compound A25) is a selective inhibitor of ROCK2, exhibiting an IC50 of 7.0 nM for ROCK2, demonstrating greater efficacy compared to ROCK1 inhibition. It exerts potent anti-fibrotic effects via the TGF-β/Smad and ROCK2/STAT3 signaling pathways. In a Bleomycin-induced mouse pulmonary fibrosis (PF) model, ROCK2-IN-12 significantly reduces collagen deposition and reverses fibrosis progression. This compound is applicable in research on pulmonary diseases such as lung fibrosis.

OSU-ERβ-12 is a selective orally active ERβ agonist capable of crossing the blood-brain barrier, exhibiting an EC50 of 78.3 nM and a Ki of 2.02 nM. It demonstrates over 200-fold selectivity for ERβ over ERα. OSU-ERβ-12 binds strongly to ERβ and reduces the expression of TGF-β-mediated profibrotic genes, thereby aiding in the reduction of liver fibrosis. This compound is useful for studying fibrotic liver diseases, non-alcoholic fatty liver disease (NAFLD), and neuroinflammation.

Tranilast Sodium has been used for the treatment of bronchial asthma. Tranilast is also used to autoimmune diseases, atopic and fibrotic pat.

GRI918013 is a compound that selectively and competitively inhibits the autocrine motility factor (ATX/NPP2), thereby suppressing tumor cell invasion and metastasis. GRI918013 binds competitively to the active site of ATX, preventing the entry of lipid substrates such as lysophosphatidylcholine (LPC). This reduces the ATX-catalyzed hydrolysis of LPC to form lysophosphatidic acid (LPA), thereby inhibiting cell invasion and metastasis associated with the ATX-LPA axis. GRI918013 exhibits an inhibitory effect on the ATX-catalyzed hydrolysis of the LPL substrate FS-3, with an IC50 of 31.42 nM and a Ki of 12.98 nM. GRI918013 can serve as a tool for studying invasion and metastasis in cancers such as melanoma, and is also suitable for research on ATX-LPA axis-related diseases, including fibrotic diseases, neuropathic pain, and cholestatic pruritus.

MnTBAP chloride (Mn(III)TBAP) is a cell-permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger that reduces the doubling time of SOD-E. coli by a factor of 2. MnTBAP chloride exhibits anti-inflammatory effects through upregulation of BMPR-II and inhibition of NFκB signaling. mnTBAP chloride is a manganese porphyrin complex with antioxidant properties and has potential for use in the study of fibrotic responses in chronic kidney diseases (CKDs).

S1P2 antagonist 1 is an orally bioavailable S1P2 antagonist used in the treatment of fibrotic diseases.

PXS-6302 is an irreversible inhibitor of lysyl oxidase with IC50s of 3.7 μM for Bovine LOX, 3.4 μM for rh LOXL1, 0.4 μM for rh LOXL2, 1.5 μM for rh LOXL3, 0.3 μM for rh LOXL4, respectively. PXS-6302 can readily penetrate the skin, reduces collagen deposition and cross-linking, and significantly improves scar appearance without reducing tissue strength. PXS-6302 also has potentially broader applications in other fibrotic diseases.

TGFβ1-IN-1 is an orally active TGF-β1 inhibitor that inhibits the production of TGF-β1-induced fibrotic markers (α-SMA and fibronectin) and can be used for the study of cancer and autoimmune diseases.

ALK5-IN-28 is a selective inhibitor of ALK-5 with an IC50 ≤ 10 nM that inhibits TGF-β-induced SMAD signalling.ALK5-IN-28 has the potential to inhibit tumour growth in vivo.ALK5-IN-28 can be used to study proliferative diseases (e.g. cancer, fibrotic diseases, systemic sclerosis).