||Emricasan, also known as IDN 6556 and PF 03491390, is a first-in-class caspase inhibitor in clinical trials for the treatment of liver diseases. Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. IDN6556 facilitates marginal mass islet engraftment in a porcine islet autotransplant model. Oral IDN-6556 may lower aminotransferase activity in patients with chronic hepatitis C. Orally-administered PF-03491390 is retained in the liver for prolonged periods with low systemic exposure, exerting a hepatoprotective effect against alpha-fas-induced liver injury in a mouse model.
||QVD-OPH, also known as Quinoline-Val-Asp-Difluorophenoxymethylketone, is a broad spectrum caspase inhibitor with potent antiapoptotic properties. Q-VD-OPh prevents neonatal stroke in P7 rat: a role for gender. Q-VD-OPh has anti-leukemia effects and can interact with vitamin D analogs to increase HPK1 signaling in AML cells. Q-VD-OPh reduces trauma-induced apoptosis and improves the recovery of hind-limb function in rats after spinal cord injury
||Z-DEVD-fmk is a cell-permeable, irreversible inhibitor of caspase-3. Caspase-3 is a cysteinyl aspartate-specific protease which plays a central role in apoptosis.
||MDK4982, also known as Z-IETD-FMK, is a potent, cell-permeable, irreversible inhibitor of caspase-8 and granzyme B., The Caspase-8 Inhibitor II controls the biological activity of Caspase-8. MDK4982 effectively inhibits influenza virus-induced apoptosis in HeLa cells. MDK4982 also inhibits granzyme B. MDK4982 has CAS#210344-98-2.
||Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor. Z-VAD-FMK inhibits caspase processing and apoptosis induction in tumor cells in vitro (IC50 = 0.0015 - 5.8 mM).
||Belnacasan, also known as VX-765, is designed to inhibit Caspase, which is an enzyme that controls the generation of two cytokines, IL-1b and IL-18. VX-765 has been shown to inhibit acute seizures in preclinical models. In addition, VX-765 has shown activity in preclinical models of chronic epilepsy. VX-765 had been dosed in over 100 patients in phase-I and phase-IIa clinical trials relating to other diseases, including a 28-day phase-IIa clinical trial in patients with psoriasis. It has completed the treatment phase of a phase-IIa clinical trial of VX-765 that enrolled approximately 75 patients with treatment-resistant epilepsy. The double-blind, randomized, placebo-controlled clinical trial was designed to evaluate the safety, tolerability and clinical activity of VX-765.
||Maraviroc is an antiviral, potent, non-competitive CKR-5 receptor antagonist that inhibits binding of HIV viral coat protein gp120. Maraviroc inhibits MIP-1β-stimulated γ-S-GTP binding to HEK-293 cell membranes, indicating its ability to inhibit chemokine-dependent stimulation of GDP-GTP exchange at the CKR-5/G protein complex. Maraviroc also inhibits the downstream event of chemokine-induced intracellular calcium redistribution.
||Resatorvid, also known as TAK-242, is a cell-permeable inhibitor of TLR4 signaling, blocking LPS-induced production of NO, TNF-α, IL-6, and IL-1β in macrophages with IC50 values of 1-11 nM. Resatorvid binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Resatorvid provides neuroprotection in experimental traumatic brain injury: implication in the treatment of human brain injury
||ASK1 Inhibitor 10 is an orally bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1). It is selective for ASK1 over ASK2 as well as MEKK1, TAK-1, IKKβ, ERK1, JNK1, p38α, GSK3β, PKCθ, and B-RAF. It inhibits streptozotocin-induced increases in JNK and p38 phosphorylation in INS-1 pancreatic β cells in a concentration-dependent manner.
||K811 is an ASK1-specific inhibitor that prolongs survival in a mouse model of amyotrophic lateral sclerosis. K811 efficiently prevented cell proliferation in cell lines with high ASK1 expression and in HER2-overexpressing GC cells. Treatment with K811 reduced sizes of xenograft tumors by downregulating proliferation markers.
||K812 is an ASK1-specific inhibitor discovered to prolong survival in a mouse model of amyotrophic lateral sclerosis.
||MSC 2032964A is a potent and selective ASK1 inhibitor (IC50 = 93 nM). It blocks LPS-induced ASK1 and p38 phosphorylation in cultured mouse astrocytes and suppresses neuroinflammation in a mouse EAE model. MSC 2032964A is orally bioavailable and brain penetrant.
||Selonsertib, also known as GS-4997, is an orally bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with potential anti-inflammatory, antineoplastic and anti-fibrotic activities. GS-4997 targets and binds to the catalytic kinase domain of ASK1 in an ATP-competitive manner, thereby preventing its phosphorylation and activation. GS-4997 prevents the production of inflammatory cytokines, down-regulates the expression of genes involved in fibrosis, suppresses excessive apoptosis and inhibits cellular proliferation.
||MDK36122, also known as H-PGDS Inhibitor I, is a Prostaglandin D Synthase (hematopoietic-type) Inhibitor. MDK36122 has no code name, and has CAS#1033836-12-2. The last 5-digit was used for name for easy communication. MDK36122 selectively blocks HPGDS (IC50s = 0.7 and 32 nM in enzyme and cellular assays, respectively) with little activity against the related human enzymes L-PGDS, mPGES, COX-1, COX-2, and 5-LOX.
||Tepoxalin, also known as ORF-20485; RWJ-20485; is a 5-lipoxygenase inhibitor potentially for the treatment of asthma, osteoarthritis (OA). Tepoxalin has in vivo inhibitory activity against COX-1, COX-2, and 5-LOX in dogs at the current approved recommended dosage.Tepoxalin inhibits inflammation and microvascular dysfunction induced by abdominal irradiation in rats. Tepoxalin enhances the activity of an antioxidant, pyrrolidine dithiocarbamate, in attenuating tumor necrosis factor alpha-induced apoptosis in WEHI 164 cells.
||Tenidap, also known as CP-66248, is a COX/5-LOX inhibitor and cytokine-modulating anti-inflammatory drug candidate that was under development by Pfizer as a promising potential treatment for rheumatoid arthritis, but Pfizer halted development after marketing approval was rejected by the FDA in 1996 due to liver and kidney toxicity, which was attributed to metabolites of the drug with a thiophene moiety that caused oxidative damage.
||PF-4191834 is a novel, potent and selective non-redox 5-lipoxygenase inhibitor effective in inflammation and pain. PF-4191834 exhibits good potency in enzyme- and cell-based assays, as well as in a rat model of acute inflammation. Enzyme assay results indicate that PF-4191834 is a potent 5-LOX inhibitor, with an IC(50) = 229 +/- 20 nM. Furthermore, it demonstrated approximately 300-fold selectivity for 5-LOX over 12-LOX and 15-LOX and shows no activity toward the cyclooxygenase enzymes. In addition, PF-4191834 inhibits 5-LOX in human blood cells, with an IC(80) = 370 +/- 20 nM.
||MK-886, also known as L 663536, is a leukotriene antagonist. It may perform this by blocking the 5-lipoxygenase activating protein (FLAP), thus inhibiting 5-lipoxygenase (5-LOX), and may help in treating atherosclerosis. MK-886 inhibits cyclooxygenase-1 activity and suppresses platelet aggregation. MK-886 induces changes in cell cycle and increases apoptosis after photodynamic therapy with hypericin. MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis.
||L 691816 is a potent inhibitor of the 5-LO reaction both in vitro and in a range of in vivo models.
||CMI-977, also know as LPD-977 and MLN-977, is a potent 5-lipoxygenase inhibitor that intervenes in the production of leukotrienes and is presently being developed for the treatment of chronic asthma. CMI-977 inhibits the 5-lipoxygenase (5-LO) cellular inflammation pathway to block the generation of leukotrienes, which play a key role in triggering bronchial asthma.
||CJ-13610 is an orally active inhibitor of 5-lipoxygenase (5-LO) . CJ-13610 inhibits the biosynthesis of leukotriene B4 and regulates the IL-6 mRNA expression in macrophages. It is efficacious in preclinical models of pain.
||BRP-7 is a 5-LO activating protein (FLAP) inhibitor.
||TT15 is an agonist of the GLP-1R.
||VU0453379 is a CNS-penetrant glucagon-like peptide 1 receptor (GLP-1R) positive allosteric modulator (PAM)