PF-05085727 is a potent, selective and brain penetrant Phosphodiesterase 2A (PDE2A) inhibitor with an IC50 of 2 nM.
Chlormethiazole is an potent and orally active GABAA agonist[1]. Chlormethiazole inhibits cytochrome P450 isoforms: CYP2A6 and CYP2E1 in human liver microsomes. Chlormethiazole is an anticonvulsant agent and has the potential for treating convulsive status epilepticus[2].
EC33 is a selective aminopeptidase A (APA) inhibitor. EC33 blocks the pressor response of exogenous Ang II. EC33 does not cross the blood-brain barrier. EC33 has the potential for salt-dependent model of hypertension research[1].
Phortress is a high affinity AhR ligand that elicits antitumor activity by inducing transcription of CYP1A1[1][2].
(S)-SBFI-26 is the (S) enantiomer of SBFI-26, an anti-nociceptive agent binds to anandamide transporters FABP5 and FABP7. (S)-SBFI-26 has anti-nociceptive and anti-inflammatory effects[1].
Trandolapril D5 (RU44570 D5) is a deuterium labeled Trandolapril (RU44570). Trandolapril is an orally active angiotensin converting enzyme (ACE) inhibitor for hypertension and congestive heart failure (CHF)[1].
H-Leu-Trp-Met-Arg-OH is a tetrapeptide. H-Leu-Trp-Met-Arg-OH can be used as a substrate for aminopeptidase-mediated hydrolysis studies[1].
Ursodeoxycholic acid-13C is the 13C labeled Ursodeoxycholic acid. Ursodeoxycholic acid (Ursodeoxycholate) is a secondary bile acid issued from the transformation of (cheno)deoxycholic acid by intestinal bacteria, acting as a key regulator of the intestinal barrier integrity and essential for lipid metabolism. Ursodeoxycholic acid acts as signaling molecule, exerting its effects by interacting with bile acid activated receptors, including G-protein coupled bile acid receptor 5 (TGR5, GPCR19) and the farnesoid X receptor (FXR). Ursodeoxycholic acid can be used for the research of a variety of hepatic and gastrointestinal diseases. Orally active[1][2].
BML-111, a lipoxin A4 analog, is a lipoxin A4 receptor agonist. BML-111 represses the activity of angiotensin converting enzyme (ACE) and increases the activity of angiotensinconverting enzyme 2 (ACE2). BML-111 has antiangiogenic, antitumor and anti-inflammatory properties[1][2].
Acetazolamide sodium is the sodium salt of Acetazolamide. Acetazolamide is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX. Acetazolamide has diuretic, antihypertensive and anti-gonococcal activities[1][4][5][6].
Entacapone is a specific, potent, peripherally acting catechol-O-methyltransferase (COMT) inhibitor with IC50 of 151 nM for PD treatment. IC50 Value: 151 nMTarget: COMTin vitro: Entacapone inhibits catechol-O-methyltransferase(COMT) with similar IC50 in different tissues including live, duodenum, kidney and lung, but entacapone is more active than tolcapone in those tissues. Entacapone (< 100 μM) is a potent inhibitor of α-syn and β-amyloid (Aβ) oligomerization and fibrillogenesis, and also protects against extracellular toxicity induced by the aggregation of both proteins in PC12 cells.in vivo: Levodopa/carbidopa/entacapone has been shown to improve the pharmacokinetic profile of levodopa and provide superior symptomatic control compared with conventional levodopa/dopa decarboxylase inhibitor therapy. We report four case histories describing clinical experience of using levodopa/carbidopa/entacapone 200/50/200 mg, one of the latest doses of this formulation, in a range of patients with Parkinson's disease. These cases illustrate that levodopa/carbidopa/entacapone 200/50/200 mg provides improvements in symptomatic control.Clinical trial: The combination product carbidopa/levodopa/entacapone (CLE) was approved in 2003 for the treatment of PD patients.
Coblopasvir (KW136, KW-136) is a novel HCV NS5A inhibitor under development for treatment of HCV infection. HCV Infection Phase 3 Clinical
h-NTPDase-IN-3 (compound 4d) is a pan-inhibitor of NTPDase with IC50s of 34.13 μM (h-NTPDase1), 0.33 μM (h-NTPDase2), 23.21 μM (h-NTPDase3), 2.48 μM (h- NTPDase8).
TPCK (L-1-Tosylamido-2-phenylethyl chloromethyl ketone; L-TPCK) is a potent serine protease inhibitor that reacts with the retinoblastoma protein (RB)-binding core of HPV-18 E7 protein and abolish its RB-binding capability. TPCK is able to modify E7 protein in live keratinocytes following its addition to the culture medium[1].
Oprozomib (ONX 0912; PR047) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.IC50 value: 36 nM/82 nM(20S proteasome β5/LMP7) [1]Target: 20S proteasomeThe anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP, as well as inhibition of migration of MM cells and angiogenesis. Oprozomib is demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It is well tolerated with repeated oral administration at doses resulting in >80% proteasome inhibition in most tissues and elicited an antitumor response in multiple human tumor xenograft and mouse syngeneic models.
ODM-204 is novel nonsteroidal dual inhibitor of both androgen receptor and CYP17A1 enzyme, with IC50s of 80 nM and 22 nM, respectively.
JG-231 is an allosteric inhibitor that disrupts the Hsp70-BAG3 interaction (Ki=0.11 uM), inhibits breast cancer cells MCF-7 and MDA-MB-231 with IC50 of 0.12 and 0.25 uM, respectively; reduces tumor burden in an MDA-MB-231 xenograft model (4 mg/kg, ip).
Ginsenoside F4 (GF4), ginseng saponinis, isolated from notoginseng or red ginseng. Ginsenoside F4 (GF4) has inhibitory effect on human lymphocytoma JK cell by inducing its apoptosis[1].Ginsenoside F4 (GF4) inhibits matrix metalloproteinase 13 (MMP 13) expression in IL-1β-treated chondrocytes and blocks cartilage breakdown in rabbit cartilage tissue culture, shows therapeutic potential for preventing cartilage collagen matrix breakdown in diseased tissues[2].
U-73122 is an inhibitor of phospholipase C (PLC), phospholipase A2, and 5-LO (5-lipoxygenase).
UK-371804 is a urokinase-type plasminogen activator (uPA) inhibitor with a Ki of 10 nM.
Z-Phe-Tyr(tBu)-diazomethylketone is a potent cathepsin L inhibitor. Z-Phe-Tyr(tBu)-diazomethylketone mediates reovirus disassembly. Z-Phe-Tyr(tBu)-diazomethylketone decreases viral detection[1][2].
EA4, a derivative of quinone, is an inhibitor for both rPLA and cPLA. EA4 can inhibit rPLA2 with a Ki value of 130 μM. EA4 can be used for the research of hemostasis, thrombosis, and erythropoiesis[1].
Azaleatin is an O-methylated flavonol isolated from Rhododendron species. Azaleatin is a dipeptidyl peptidase-IV inhibitor. Azaleatin can be used for the research of type-2 diabetes and obesity[1][2].
Doxycycline (hyclate) is a tetracycline antibiotic and broad-spectrum metalloproteinase (MMP) inhibitor.
HDAC/HSP90-IN-3 (compound J5) is a potent and selective fungal Hsp90 and HDAC dual inhibitor, with IC50 values of 0.83 and 0.91 μM, respectively. HDAC/HSP90-IN-3 shows antifungal activity against azole resistant C. albicans. HDAC/HSP90-IN-3 can suppress important virulence factors and down-regulate drug-resistant genes ERG11 and CDR1[1].
Andolast is an anti-allergic agent for the treatment of bronchial asthma, chronic obstructive pulmonary disease (COPD). Andolast inhibits dose dependently guinea-pig lung cAMP-phosphodiesterase with an IC50 of 50 mM.
Diprotin A (TFA) is an inhibitor of dipeptidyl peptidase IV (DPP-IV).
KRIBB11 is an inhibitor of Heat shock factor 1 (HSF1), with IC50 of 1.2 μM.
Salvianolic acid A could protect the blood brain barrier through matrix metallopeptidase 9 (MMP-9) inhibition and anti-inflammation.
PF-3845 is a selective fatty acid amide hydrolase (FAAH) inhibitor (Ki = 0.23 μM); showing negligible activity against FAAH2.IC50 value: 0.23 uMTarget: FAAHPF-3845 selectively inhibits FAAH by carbamylating FAAH's serine nucleophile [1]. PF-3845 treated mice (10 mg/kg, i.p.) shows rapid and complete inactivation of FAAH in the brain, as judged by competitive activity-based protein profiling (ABPP) with the serine hydrolase-directed probe fluorophosphonate (FP)-rhodamine. PF-3845 shows a long duration of action up to 24 hour. PF-3845-treated mice also shows dramatic (>10-fold) elevation in brain levels of AEA and other NAEs (N-pamitoyl ethanolamine [PEA] and N-oleoyl ethanolamine [OEA]). FAAH is AEA-degrading enzyme fatty acid amide hydrolase. PF-3845 (1–30 mg/kg, oral administration [p.o.]) causes a dose dependent inhibition of mechanical allodynia with a minimum effective dose (MED) of 3 mg/kg (rats are analyzed at 4 hour post dosing with PF-3845). At higher doses (10 and 30 mg/kg), PF-3845 inhibits pain responses to an equivalent, if not greater, degree than the nonsteroidal anti-inflammatory drug naproxen (10mg/kg, p.o.) [1]. PF-3845 (10 mg/kg, i.p.) significantly reverses LPS-induced tactile allodynia, but doesn't modify paw withdrawal thresholds in the saline-injected paw [2].