Allamandicin is an iridoid lactones. Allamandicin can be isolated from the roots of Allamanda cathartica. Allamandicin is an inhibitor of tyrosinase[1].
Enpp-1-IN-8 is a potent inhibitor of ectonucleotide pyrophosphatase-phosphodiesterase 1 (enpp-1). The ENPP 1 has broad specificity and can cleave a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds nucleotides and nucleotide sugars. Enpp-1-IN-8 has the potential for the research of cancer and infectious diseases (extracted from patent WO2021203772A1, compound 51)[1].
2,5-Di-tert-butylhydroquinone (DTBHQ), the indirect food additive, regulates the activity of 5-lipoxygenase as well as the activity of COX-2 (IC50=1.8 and 14.1 μM for 5-LO and COX-2, respectively) [1].
Z-FG-NHO-Bz is a selective cathepsin inhibitor[1].
F1063-0967 is a Dual-specificity phosphatase 26 (DUSP26) inhibitor with an IC50 of 11.62 μM.
4-Hydroxynonenal (4-HNE) is an α,β unsaturated hydroxyalkenal and an oxidative/nitrosative stress biomarker. 4-Hydroxynonenal is a substrate and an inhibitor of acetaldehyde dehydrogenase 2 (ALDH2). 4-Hydroxynonenal can modulate a number of signaling processes mainly through forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and membrane lipids. 4-Hydroxynonenal plays an important role in cancer through mitochondria[1][2][3].
GMX1778(CHS-828) is a potent inhibitor of NAD+ biosynthesis enzyme NAMPT with IC50 <25 nM.IC50 value: < 25 nM [1]Target: NAMPT inhibitorin vitro: The phosphoribosyltransferase activity of recombinant NAMPT was sensitive to inhibition by GMX1778 (IC50 < 25 nM) whereas the adenyltransferase activity of recombinant NMNAT1 was not. The Kd of recombinant NAMPT for GMX1778 labeled with a fluorescent tag (GMX1778-Alexa Fluor) was 120 nM. Overexpression of wild-type NAMPT was able to maintain a certain level of NAD+ under conditions of challenge with 3 nM GMX1778, but this effect was lost when cells were exposed to 300 nM GMX1778 [1]. GMX1778 increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD(+) level. Notably, GMX1778 treatment does not induce ROS in normal cells. GMX1778-induced ROS can be diminished by adding nicotinic acid (NA) in a NA phosphoribosyltransferase 1 (NAPRT1)-dependent manner [2].in vivo: A 4-h iv infusion of NA (120 mg/kg of body weight) did not adversely affect the antitumor activity of a 24-h iv infusion of GMX1777 at a dose of 150 mg/kg or 650 mg/kg in the NAPRT1-deficient xenograft experiments. GMX1777 at 650 mg/kg is above the maximum tolerated dose. The administration of NA as a 4-h iv infusion immediately following treatment with 750 mg/kg GMX1777 reduced the mortality associated with toxic doses of GMX1777 [1].
Palmitic acid-d4-2 is the deuterium labeled Palmitic acid. Palmitic acid is a long-chain saturated fatty acid commonly found in both animals and plants. PA can induce the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in in mouse granulosa cells[1][2].
PCSK9-IN-22 (compound 29) is an orally active inhibitor of PCSK9. PCSK9-IN-22 inhibits the interaction of the protein with LDLR in vivo[1].
AZD 4407 is a potent 5-lipoxygenase inhibitor.
Tyrphostin 8 is a tyrosine kinase, with an IC50 of 560 μM for EGFR kinase. Tyrphostin 8 is also a GTPase inhibitor. Tyrphostin 8 can inhibit the protein serine/threonine phosphatase calcineurin (IC50=21 μM)[1][2][3].
Perindopril erbumine is a potent ACE inhibitor of which is used to treat high blood pressure, heart failure or stable coronary artery disease.Target: ACEPerindopril is a long-acting ACE inhibitor. It is used to treat high blood pressure, heart failure or stable coronary artery disease in form of perindopril arginine (trade names include Coversyl, Coversum) or perindopril erbumine (trade name Aceon). According to the Australian government's Pharmaceutical Benefits Scheme website, based on data provided to the Australian Department of Health and Aging by the manufacturer, perindopril arginine and perindopril erbumine are therapeutically equivalent and may be interchanged without differences in clinical effect. However the dose prescribed to achieve the same effect will differ due to different molecular weights for the two forms. Perindopril is one of the most prescribed inhibitors of angiotensin converting enzyme, has a large evidence base, which allows to use it in patients with hypertension, diabetes mellitus type 2, coronary heart disease and chronic heart failure. In this review, the author focused on the evidence of organoprotecting properties of perindopril that lie outside lowering blood pressure.
O-Desisobutyl-O-n-propyl Febuxostat, extracted from the patent CN 103467412, is an xanthine oxidase inhibitor[1].
Pimobendan hydrochloride is a selective inhibitor of PDE3 with IC50 of 0.32 μM.Target: PDE3Pimobendan exhibits selective inhibition of PDE III isolated from guinea pig cardiac muscle with IC50 of 0.32 uM compared to the inhibition of PDE I and PDE II (IC50s >30 μM). In human atrial cells, 100 μM pimobendan significantly increases the L-type calcium current (ICa(L)) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4% with the half-maximal stimulation (EC50) of 1.13 μM. In rabbit atrial cells, Pimobendan increases ICa(L) at +10 mV by 67.4.%, which is significantly lower than that obtained in human atrial cells Pimobendan shows a beneficial effect on survival in the murine model of EMC virus-induced myocarditis. Administration of Pimobendan significantly increases the final survival rate from 33.6% (control) to 53.3% (0.1 mg/kg) or 66.7% (1 mg/kg). Pimobendan (1 mg/kg) also significantly reduces myocardial cellular infiltration, the level of intracardiac tumor necrosis factor (TNF)-α and interleukin (IL)-1β compared with the control group, which shows no effect on myocardial necrosis, heart weight and body weight. Pimobendan suppresses expression of the intracardiac iNOS gene , causing reduction of intracardiac NO production.
MG-115 is a potent and reversible proteasome inhibitor, with Kis of 21 nM and 35 nM for 20S and 26S proteasome, respectively. MG-115 specifically inhibit the chymotrypsin-like activity of the proteasome, induces p53-dependent apoptosis[1][2][3].
P7C3 is a NAMPT activator. P7C3 can enhance learning and memory in aged rats. Protects newborn neurons in the dentate gyrus by mitigating cell death. In vitro: Administration of active P7C3 chemicals to cells treated with doxorubicin, which induces NAD depletion, led to a rebound in intracellular levels of NAD and concomitant protection from doxorubicin-mediated toxicity. In vivo: P7C3 is orally bioavailable, crosses the blood-brain barrier, and is non-toxic at doses several fold higher than the efficacious dose.An easily administered pro-neurogenic compound. The administration of P7C3 is 10mg/ kg( IP) in rats. Administration of P7C3 to normal mice, as well as npas3-/- mice, enhance survival of neurons subsequent to their birth in the SGZ.
Serotonin-d4 is deuterium labeled Serotonin. Serotonin is a monoamine neurotransmitter in the CNS and an endogenous 5-HT receptor agonist. Serotonin is also a catechol O-methyltransferase (COMT) inhibitor with a Ki of 44 μM.
Benzbromarone is a highly effective and well tolerated non-competitive inhibitor of xanthine oxidase, used as an uricosuric agent, used in the treatment of gout.
SYC-435 (SYC435) is a potent inhibitor of mutant IDH1, binds at the isocitrate pocket of mutated IDH1 with Ki values of 190 nM against IDH1 R132H and 120 nM against IDH1 R132C; SYC-435 is cell active and capable of significantly reducing D-2-HG production in an HT1080 fibrosarcoma cell line expressing IDH1 R132C (IC50=2.4 uM).
Lerodalcibep (LIB003) is a recombinant fusion protein of a PCSK9-binding domain (adnectin) and human serum albumin. Lerodalcibep is a Lipid-lowering agent. Lerodalcibep can be used for the research of hypercholesterolemia and cardiovascular diseases[1].
2-D08 is a cell permeable, mechanistically unique inhibitor of protein SUMOylation. 2-D08 also inhibits Axl with an IC50 of 0.49 nM.
Arimoclomol citrate (BRX-220 citrate) is a co-inducer of heat shock proteins (HSP)[1]. Arimoclomol citrate protects motor neurons by enhancing Hsp expression, thus directly affecting protein aggregation and clearance of misfolded assemblies via the proteasome-ubiquitin system[2].
Bictegravir is a novel, potent inhibitor of HIV-1 integrase with an IC50 of 7.5 nM.
SHR168442 is a modulator of retinoid-related orphan receptor gamma (RORγ) with an IC50 value of 0.035 μM.
IDO-IN-5 (NLG-1489) is an indoleamine 2,3-dioxygenase (IDO) inhibitor extracted from patent WO WO2012142237A1, compound 1489, has an IC50 of 1-10 μM.
CTS-1027 is a potent small molecule inhibitor of MMPs, with IC50s of 0.3 nM, 0.5 nM for MMP2, MMP13, respectively, and has > 1,000 fold selectivity over MMP1.
GI254023X is a potent MMP9 and ADAM10 inhibitor with IC50s of 2.5 and 5.3 nM, respectively.
Finasteride-d9 is deuterium labeled Finasteride. Finasteride (MK-906) is a potent and competitive 5α-reductase inhibitor, with an IC50 of 4.2 nM for type II 5α-reductase. Finasteride has approximately a 100-fold greater affinity for type II 5α-reductase enzyme than for the type I enzyme. Finasteride can be used for the research of benign prostatic hyperplasia (BPH) and androgenic alopecia[1][2][3].
Thrombin inhibitor 5 (compound 385) is a thrombin inhibitor, with IC50s ranging from 0.1 μM to 1 μM. Thrombin inhibitor 5 can be used for research of venous thromboembolism[1].
3,5-Difluoro-L-tyrosine is a functional, tyrosinase-resistant mimetic of tyrosine. 3,5-Difluoro-L-tyrosine can be used to analyze the substrate specificity of protein tyrosine phosphatases (PTPs)[1].