L-Eflornithine is an irreversible ornithine decarboxylase (ODC) inhibitor with a KD of 1.3±0.3 μM, and a Kinact of 0.15±0.03 min-1. L-Eflornithine is an enantiomer of Eflornithine.

Niaprazine is a histamine H1-receptor antagonist with marked sedative properties. Niaprazine has antihistamine and antiserotonin activities and can be used for sleep disorder research[1][2]. Niaprazine exhibits a low affinity for the vesicular monoamine transporter and for D2, α2, β, H1 and mAch receptors. Niaprazine, particularly the (+)stereoisomer, has a higher affinity for α1 (Ki = 77 nM) and 5-HT2 (Ki = 25 nM) binding sites, but is poorly recognized by 5-HT1A and 5-HT1B binding sites[2]. Niaprazine (60 mg/kg; i.p.; once) treatment increases rat brain 5-hydroxyindole acetic acid (5-HIAA) concentrations 30 min after treatment, and reduced them at 3-8 hr after treatment. Niaprazine also produces a short-lasting depletion of rat brain noradrenaline (NA) and dopamine (DA)[3]. Animal Model: Male Sprague-Dawley rats (150-200 g)[3] [1]. D Scherman, et al. Molecular pharmacology of niaprazine. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(6):989-1001. [2]. P G Rossi, et al. Niaprazine in the treatment of autistic disorder. J Child Neurol. 1999 Aug;14(8):547-50. [3]. P E Keane, et al. The effect of niaprazine on the turnover of 5-hydroxytryptamine in the rat brain. Neuropharmacology. 1982 Feb;21(2):163-9.

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 dihydrochloride inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 . RWJ-56110 dihydrochloride blocks angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 dihydrochloride induces cell apoptosis[1][2]. Proteinase-activated receptors (PARs) are a family of G protein-coupled receptors activated by the proteolytic cleavage of their N-terminal extracellular domain, exposing a new amino terminal sequence that functions as a tethered ligand to activate the receptors.RWJ56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM) while being quite selective relative to collagen and the thromboxane mimetic U46619 [1].RWJ-56110 dihydrochloride is fully inhibits thrombin-induced RASMC proliferation with an IC50 value of 3.5 μM. RWJ-56110 dihydrochloride shows blockade of thrombin's action with RASMC calcium mobilization (IC50=0.12 μM), as well as with HMVEC (IC50=0.13 μM) and HASMC calcium mobilization (IC50=0.17 μM)[1].RWJ56110 (0.1-10 μM; 24-96 hours) inhibits endothelial cell growth dose-dependently, with half-maximal inhibitory concentration of RWJ56110 is approximately 10 μM[2].RWJ56110 (0.1-10 μM; 6 hours) inhibits DNA synthesis of endothelial cells in a thymidine incorporation assays. Endothelial cells are in fast-growing state (50-60% confluence), RWJ56110 inhibits cell DNA synthesis in a dose-dependent manner, but when cells that are in the quiescent state (100% confluent), the inhibitory effect of PAR-1 antagonists is much less pronounced[2].RWJ56110 (0.1-10 μM; pretreatment for 15 min) inhibits thrombin-induced Erk1/2 activation in a concentration-dependent manner. However, when endothelial cells are stimulated by FBS (final concentration 4%), it reduces partially the activated levels of Erk1/2[2].RWJ56110 (30 μM; 24 hours) has an inhibitory effect on endothelial cell cycle progression. It reduces the percentage of cells in the S phase, while alterations in the percentages of G1 and G2/M cells are less pronounced[2]. Western Blot Analysis[2] Cell Line: Endothelial cells [1]. Andrade-Gordon, et al.Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. oc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62. [2]. Panagiota Zania, et al. Blockade of angiogenesis by small molecule antagonists to protease-activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006 Jul;318(1):246-54.

CK2-IN-9, a potent and selective CK2 kinase inhibitor, exhibits an inhibitory concentration (IC50) of 3 nM against its target enzyme and hampers Wnt reporter activity with an IC50 of 75 nM. In rats, it demonstrates low exposure (AUC=0.36 μM/h) and high clearance (CL=65 mL/min/kg) [1].

PDE5-IN-10 (compound 4b), a potent phosphodiesterase type 5 (PDE5) inhibitor, exhibits an effective half-maximal inhibitory concentration (IC50) of 20 nM, enhanced in vitro microsomal stability (t 1/2 = 44.6 min), and excellent efficacy in restoring long-term potentiation, making it suitable for Alzheimer’s disease (AD) research [1].

Spirorenone is an androstadienone derivative as a highly effective aldosterone antagonist. Spirorenone is 8.6 times as potent as spironolactone, but showed a lower affinity for the mineralocorticoid receptors. In phase I clinical trials Spirorenone was absorbed with a half-life of 20-30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1-2 h. Disposition of the parent drug was biphasic with half-lives of 50-60 min (distribution) and 5-6 h (elimination). Neither significant accumulation nor enzyme induction was observed after prolonged treatment.

NOD1/2 Antagonist-1 is a potent dual inhibitor of nucleotide-binding oligomerization domain-like receptors 1 and 2 (NOD1/2), displaying inhibitory concentrations (IC50) of 1.13 μM for NOD1 and 0.77 μM for NOD2. It exhibits an acceptable half-life (T1/2) of 67.6 minutes. Additionally, NOD1/2 Antagonist-1 enhances the antitumor efficiency of Paclitaxel (PTX).

SB 242084 hydrochloride is a 5-HT2C receptor antagonist(pKi=9.0) that displays 158- and 100-fold selectivity over 5-HT2A and 5-HT2B receptors respectively.IC50 value: 9.0(pKi) [1]Target: 5-HT2C antagonistin vitro: SB 242084 had over 100-fold selectivity over a range of other 5-HT, dopamine and adrenergic receptors. In studies of 5-HT-stimulated phosphatidylinositol hydrolysis using SH-SY5Y cells stably expressing the cloned human 5-HT2C receptor, SB 242084 acted as an antagonist with a pKb of 9.3, which closely resembled its corresponding receptor binding affinity [1].in vivo: SB 242084 potently inhibited m-chlorophenylpiperazine (mCPP, 7 mgkg i.p. 20 min pre-test)-induced hypolocomotion in rats, a model of in vivo central 5-HT2C receptor function, with an ID50 of 0.11 mg/kg i.p., and 2.0 mg/kg p.o. SB 242084 (0.1-1 mg/kg i.p.) exhibited an anxiolytic-like profile in the rat social interaction test, increasing time spent in social interaction, but having no effect on locomotion. SB 242084 (0.1-1 mg/kg i.p.) also markedly increased punished responding in a rat Geller-Seifter conflict test of anxiety, but had no consistent effect on unpunished responding [1].

PI3Kα-IN-4 is a potent, selective, and orally active PI3Kα inhibitor, demonstrating an IC50 of 1.8 nM and exhibiting antitumor activity[1].

PF-06843195 is a selective PI3Kα inhibitor, demonstrating potent activity with an IC50 of 18 nM in Rat1 fibroblasts and Kis for PI3Kα and PI3Kδ less than 0.018 nM and 0.28 nM, respectively, in biochemical kinase assays. It effectively suppresses the PI3K/mTOR signaling pathway and exhibits durable antitumor efficacy[1].

A2AR-antagonist-1 (compound 38), an orally active adenosine A2A receptor antagonist with an IC50 value of 29 nM, demonstrates anti-tumor properties and stability in mouse liver microsomes (t1/2 = 86.1 min). Additionally, it activates T cells by inhibiting immunosuppressive molecules (LAG-3 and TIM-3) and promoting expression of effector molecules (GZMB, IFNG, and IL-2) [1].

Teneligliptin (MP-513) is a potent chemotype prolylthiazolidine-based DPP-4 inhibitor, which competitively inhibits human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50s of approximately 1 nM. Teneligliptin (MP-513) inhibits all these DPP-4 enzymes in a concentration-dependent manner. The IC50s of Teneligliptin (MP-513) for rhDPP-4, human plasma, and rat plasma are 0.889, 1.75, and 1.35 nM, respectively. A study of enzyme inhibition kinetics is conducted for Teneligliptin (MP-513) using Gly-Pro-MCA as the substrate and rhDPP-4 as the enzyme source. Plots based on the Michaelis-Menten equation reveals that Teneligliptin (MP-513) inhibits DPP-4 in a substrate-competitivemanner; the residual sum of squares for competitive and non-competitive models is 0.162 and 0.192, respectively. Ki, Km, and Vmax values are 0.406 nM, 24 μM, and 6.06 nmol/min, respectively. Teneligliptin (MP-513) inhibits the degradation of GLP-1(7-36)amide with an IC50 of 2.92 nM[1]. Oral administration of Teneligliptin (MP-513) in Wistar rats results in the inhibition of plasma DPP-4 with an ED50 of 0.41 mg/kg. Plasma DPP-4 inhibition is sustained even at 24 h after administration of Teneligliptin (MP-513). An oral carbohydrate-loading test in Zucker fatty rats shows that Teneligliptin (MP-513) at ≥0.1 mg/kg increases the maximum increase in plasmaglucagon-like peptide-1 and insulin levels, and reduces glucose excursions. This effect is observed over 12 h after a dose of 1 mg/kg. An oral fat-loading test in Zucker fatty rats also shows that Teneligliptin (MP-513) at 1 mg/kg reduces triglyceride and free fatty acid excursions. In Zucker fatty rats, repeated administration of Teneligliptin (MP-513) for two weeks reduces glucose excursions in the oral carbohydrate-loading test and decreased the plasma levels of triglycerides and free fatty acids under non-fasting conditions. Oral administration of Teneligliptin (MP-513) inhibits plasma DPP-4 in rats in a dose-dependent manner. The ED50 value for Teneligliptin (MP-513) is calculated to be 0.41 mg/kg, while those for Sitagliptin and Vildagliptin, 27.3 and 12.8 mg/kg, respectively[1]. Teneligliptin (MP-513) improves the histopathological appearance of the liver and decreases intrahepatic triglyceride levels in an NAFLD model mouse, which is associated with downregulation of hepatic lipogenesis-related genes due to AMPK activation[2]. [1]. Fukuda-Tsuru S, et al. A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol. 2012 Dec 5;696(1-3):194-202. [2]. Ideta T, et al. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice. Int J Mol Sci. 2015 Dec 8;16(12):29207-18.

Piperazine (2HCl) is gamma-aminobutyric acid (GABA) agonists and its major effects appear to be on the central nervous system. Piperazine was the anthelmintic with the greatest number of reports of toxicoses and suspected toxicoses in cats. Piperazine neurotoxicity in cats and dogs usually was manifested by muscle tremors, ataxia, and/or behavioral disturbances within 24 hours after estimated daily dose(s) between 20 and 110 mg/kg[1]. For di-substituted derivatives, ciprofloxacin was selected and hybrids were synthesized via substitution at piperazinyl-N4. The reaction of piperazinyl-NH of ciprofloxacin with selected drugs resulted in pronounced growth inhibition of standard as well as resistant bacterial strains[2]. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 μΜ, respectively)[3]. Piperazine adipate (10 mM) causes mortality of A. galli and H. gallinae after a maximum of 30 min exposure, inhibits malate oxidation by 78%, and inhibits aldolase activity in both parasites. Piperazine adipate (10 mM) also inhibits cholinesterase activity by 96% in Ascaridia galli (A. galli) and 93% in Heterakis gallinae (H. gallinae). Piperazine adipate inhibits oxaloacetate reduction by 26% and 55% in A. galli and H. gallinae, resepctively[4].

MK-3207 is a potent and orally bioavailable CGRP receptor antagonist (IC 50 = 0.12 nM; K i = 0.024 nM); highly selective versus human AM1, AM2, CTR, and AMY3. IC50 Value: 0.024 nM (Ki, Human CGRP) [1] As other CGRP receptor antagonists, MK-3207 shows a lower affinity for human CGRP receptors from other species, including canine and rodent. in vitro: MK-3207 is a potent antagonist of the human and rhesus monkey CGRP receptors (K(i) = 0.024 nM). in vivo: MK-3207 produced a concentration-dependent inhibition of dermal vasodilation, with plasma concentrations of 0.8 and 7 nM required to block 50 and 90% of the blood flow increase, respectively. The tritiated analog [3H]MK-3207 was used to study the binding characteristics on the human CGRP receptor. [3H]MK-3207 displayed reversible and saturable binding (K(D) = 0.06 nM), and the off-rate was determined to be 0.012 min(-1), with a t(1/2) value of 59 min [1]. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5 mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100 mg) were continued into the second stage [2]. Clinical trial: MK-3207 for the treatment of acute migraines. Phase 2b

PKI-179 is a potent, orally active compound that functions as a dual PI3K/mTOR inhibitor. It demonstrates IC50 values of 8 nM for PI3K-α, 24 nM for PI3K-β, 74 nM for PI3K-γ, 77 nM for PI3K-δ, and 0.42 nM for mTOR. Additionally, it is effective against E545K and H1047R mutations, with IC50s of 14 nM and 11 nM, respectively. In vivo studies have shown that PKI-179 possesses anti-tumor capabilities[1][2].

ARN-21934 is a potent, highly selective, blood-brain barrier (BBB) penetrant inhibitor for human topoisomerase II α over β. ARN-21934 inhibits DNA relaxation with an IC50 of 2 μM as compared to the anticancer agent Etoposide (IC50=120 μM). ARN-21934 exhibits a favorable in vivo pharmacokinetic profile and is a promising lead compound for anticancer research[1]. ARN-21934 display a different affinity for topoIIα and topoIIβ. ARN-21934 is more potent against the α isoform, the IC50 value for the inhibition of DNA relaxation by topoIIα is 2 μM, the value for inhibition of DNA relaxation by topoIIβ is 120 μM[1].ARN-21934 exhibits a small panel of human cancer cell lines. It against melanoma (A375 and G-361), breast (MCF7), endometrial (HeLa), lung (A549), and androgen-independent prostate (DU145) cancer cells with IC50 values of 12.6 μM, 8.1 μM, 15.8 μM, 38.2 μM, 17.1 μM, and 11.5 μM, respectively[1]. ARN-21934 (intraperitoneal injection; 10 mg/kg; single dose) reaches a maximal plasma concentration of 0.68 μg/mL after 15 min. The half-life is 149 min in circulation, still being present in plasma 360 min after injection. The compound also exhibits good clearance values (0.116 L/(min kg)). Besides, ARN-21934 is able to reach the brain, with a maximum concentration of compound at 60 min, and is still present in the brain 360 min after injection[1] [1]. Jose Antonio Ortega, et al. Novel, Potent, and Druglike Tetrahydroquinazoline Inhibitor That Is Highly Selective for Human Topoisomerase II α over β. J Med Chem. 2020 Nov 12;63(21):12873-12886.

UR-2922 is an oral antagonist of platelet GPIIb/IIIa. UR-2922 possessed a high affinity for the human platelet receptor (K(d) <1 nM) and a slow dissociation rate (k(off)= 90 min) in vitro. UR-2922 induced no ligand-induced binding sites (LIBS) expression

Adrenomedullin (22-52) is a C-terminal fragment of adrenomedullin (1-52) . In vitro, adrenomedullin (22-52) reduces basal corticosterone production in a mixture of rat adrenocortical and adrenomedulllary cells. It also reverses increases in ACTH-stimulated corticosterone production induced by adrenomedullin (1-52). Adrenomedulin (22-52) (0.5 and 5 μg/kg/min) has no effect on basal regional cerebral blood flow but reverses increases in regional cerebral blood flow induced by rat adrenomedullin in rats. Unlike adrenomedullin (1-52), adrenomedullin (22-52) has no effect on mesenteric arterial perfusion pressure in cats.

Rp-cAMPS sodium salt, a cAMP analog, is a potent, competitive cAMP-induced activation of cAMP-dependent PKA I and II (Kis of 12.5 μM and 4.5 μM, respectively) antagonist. Rp-cAMPS sodium salt is resistant to hydrolysis by phosphodiesterases[1][2][3][4][5][6]. A membrane-permeable competitive cAMP antagonist (Rp-cAMPS) that blocks PKA activation by binding to the regulatory subunits without dissociating the kinase holoenzyme also inhibits synaptic plasticity but has no effect on normal synaptic transmission[2]. Rp-cAMPS (10 μM, 15 min) decreases the monosynaptic EPSCs evoked at the PB-CeLC and BLA-CeLC synapses in slices from arthritic rats but not in control neurons from normal animals. The inhibitory effect of Rp-cAMPS is significant compared to predrug (ACSF) control values obtained in the same neurons[2]. [1]. R J de Wit, et al. Inhibitory action of certain cyclophosphate derivatives of cAMP on cAMP-dependent protein kinases. Eur J Biochem. 1984 Jul 16;142(2):255-60. [2]. Rothermel JD, et al. A mechanistic and kinetic analysis of the interactions of the diastereoisomers of adenosine 3’,5’-(cyclic)phosphorothioate with purified cyclic AMP-dependent protein kinase. Biochem J. 1988 May 1;251(3):757-62.[3]. Fu Y, et al. PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior. Mol Pain. 2008 Jul 16;4:26.[4]. Kuriyama S, et al. Isoproterenol inhibits rod outer segment phagocytosis by both cAMP-dependent and independent pathways. Invest Ophthalmol Vis Sci. 1995 Mar;36(3):730-6.[5]. Dostmann WR, et al. Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3’,5’-cyclic phosphorothioates. J Biol Chem. 1990 Jun 25;265(18):10484-91.[6]. Van Haastert PJ, et al. Competitive cAMP antagonists for cAMP-receptor proteins. J Biol Chem. 1984 Aug 25;259(16):10020-4.

Sarpogrelate hydrochloride (MCI-9042) , a selective 5-HT2 antagonist, has been widely used as an anti-platelet agent for the treatment of PAD. Target: 5-HT2 Recepter Sarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. Sarpogrelate hydrochloride was shown to have the same affinity as ritanserin for 5-HT2A receptors, with a Ki value of 8.39 nM. Sarpogrelate hydrochloride lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49). After 12 weeks of sarpogrelate administration, FBF and LBF responses during RH showed significant increases from 13.2 +/- 1.7 to 18.1 +/- 2.2 mL/min per 100 mL tissue (P < 0.01) and from 8.2 +/- 0.9 to 14.2 +/- 2.1 mL/min per 100 mL tissue (P < 0.05), respectively. Sarpogrelate hydrochloride -induced augmentation of FBF and LBF responses to RH was maintained at 24 weeks. Long-term oral administration of sarpogrelate improves vascular function in patients with PAD.

L-Eflornithine is an irreversible ornithine decarboxylase (ODC) inhibitor with a KD of 1.3±0.3 µM, and a Kinact of 0.15±0.03 min-1. L-Eflornithine monohydrochloride (L-DFMO monohydrochloride) is an enantiomer of Eflornithine.

CC-90005 is a potent, selective and orally active inhibitor of protein kinase C-θ (PKC-θ), with an IC50 of 8 nM. CC-90005 shows selectivity for PKC-θ over PKC-δ (IC50=4440 nM). CC-90005 can inhibit T cell activation by IL-2 expression[1]. CC-90005 shows the exquisite selectivity of CC-90005, with IC50s for all other family members of >3 μM[1].CC-90005 is a moderate inhibitor of both CYP2C9 (IC50=8 μM) and CYP2C19 (IC50=5.9 μM) in human liver microsomes[1].CC-90005 inhibits IL-2 expression in LRS_WBC human PBMCs, with an IC50 of 0.15 μM[1].CC-90005 (1-10 μM; 24 h) inhibits T cell proliferation in PBMCs by 51% at 1 μM and 88% at 3 μM[1]. CC-90005 (3-30 mg/kg; p.o. twice daily for 4 days) significantly reduces the popliteal lymph node (PLN) size in a model of chronic T cell activation[1].CC-90005 (100 mg/kg; a single p.o.) significantly inhibits plasma and spleen IL-2 release by 51 and 54%, respectively[1].CC-90005 exhibits reasonable oral bioavailability (66 and 46%) and Cmax (1.18 and 1.2 μM) following oral administration (10 and 3 mg/kg) in rat and dog, respectively[1].CC-90005 exhibits the mean residence time (0.52 and 2.0 h), CL (69.1 and 20.5 mL/min/kg) and Vss (2.11 and 2.44 L/kg) following intravenous administration (2 and 1 mg/kg) in rat and dog, respectively[1]. [1]. Papa P, et, al. Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005. J Med Chem. 2021 Aug 26;64(16):11886-11903.

Hydrochloride salt of dTAGV-1. Suitable for use in vivo. Following ip administration of 10 mg/kg in mice: T = 4.43 h; Cmax = 2123 ng mL-1; AUCinf = 18517 hr*ng mL-1 and CL = 9.05 mL min-1 kg-1 Negative control dTAGV-1-NEG also available. Important: It is recommended that DMSO stock solutions of this compound are made and used on the same day and are not subjected to freeze/thaw.

PRMT5-IN-31 (Compound 3m), a selective PRMT5 inhibitor (IC50: 0.31 μM), increases hnRNP E1 protein levels by occupying the substrate site of PRMT5 and establishing key interactions with amino acid residues. It exhibits antiproliferative properties against A549 cells through induction of apoptosis and inhibition of cell migration, while demonstrating high metabolic stability in human liver microsomes (T1/2: 132.4 min) [1].

IRAK4-IN-25 (compound 38), a potent oral IRAK4 inhibitor (IC50 = 7.3 nM) with low clearance (Cl = 12 mL/min/kg), effectively suppresses pro-inflammatory cytokine production and demonstrates favorable in vitro safety and ADME profiles. It is suitable for research on inflammatory and autoimmune disorders [1].

RK-52 is a synthetic inhibitor of rhodesain, characterized by an impressive ksecond value (ksecond = 67000 × 103 M−1 min−1) and by a picomolar affinity toward the trypanosomal protease (Ki = 38 pM).

AM679 is a potent and selective FLAP inhibitor with IC50s of 2.2 nM/0.6 nM/154 nM for FLAP binding/hLA/hWB respectively. IC50 value: 2.2 nM/0.6 nM/154 nM(FLAP binding/hLA/hWB) [1] AM679 showed an improved CYP inhibition profile (IC50 3A4 = 16.7 lM, 2C9 =

Sarpogrelate-d3 HCl is a deuterated compound of Sarpogrelate HCl. Sarpogrelate HCl has a CAS number of 135159-51-2. Sarpogrelate(MCI-9042) hydrochloride, a selective 5-HT2 antagonist, has been widely used as an anti-platelet agent for the treatment of PAD. Target: 5-HT2 Recepter Sarpogrelate is a drug which acts as an antagonist at the 5HT2A and 5-HT2B receptors. Sarpogrelate was shown to have the same affinity as ritanserin for 5-HT2A receptors, with a Ki value of 8.39 nM. Sarpogrelate lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49). After 12 weeks of sarpogrelate administration, FBF and LBF responses during RH showed significant increases from 13.2 +/- 1.7 to 18.1 +/- 2.2 mL/min per 100 mL tissue (P < 0.01) and from 8.2 +/- 0.9 to 14.2 +/- 2.1 mL/min per 100 mL tissue (P < 0.05), respectively. Sarpogrelate-induced augmentation of FBF and LBF responses to RH was maintained at 24 weeks. Long-term oral administration of sarpogrelate improves vascular function in patients with PAD.

LEO 39652, a dual-soft PDE4 inhibitor, demonstrates potent inhibition of PDE4 subtypes A, B, C, and D with respective IC50 values of 1.2 nM, 1.2 nM, 3.0 nM, and 3.8 nM. Additionally, it inhibits TNF-α with an IC50 of 6.0 nM, indicating its potential for topical Atopic dermatitis (AD) research [1].

The truncated glucagon-like peptides GLP-1(7-37) is naturally occurring peptide product of the preproglucagon gene that are synthesized primarily in the intestine and acts as incretin that are released from the intestine into the bloodstream in response to food and stimulate insulin secretion. GLP-1(7-37) produced a dose-related enhancement of the glucose-stimulated increase in plasma insulin concentration and an increased rate of glucose infusion in Sprague-Dawley Rats at a dosing rang of 0.5, 5, or 50 pmol/min/kg. Further, infusion of GLP-1(7-37) for 60 mins produced a small transitory increase in plasma insulin concentration in fasted rats and fed rats and a slight transitory decrease in plasma glucose concentration. Moreover, GLP-1(7-37) (5 pmol/min/kg IV) infusion for 6 h in Sprague-Dawley rats produced a sustained increase in plasma insulin concentration relative to levels in rats infused with vehicle[1].

TP0597850, a selective MMP2 inhibitor with an IC50 value of 0.22 nM, demonstrates a prolonged dissociation half-life from MMP2 (t1/2 = 265 minutes) [1].

Integrin modulator 1 is a potent and selective α4β1 integrin agonist, with an IC50 of 9.8 nM for RGD-binding α4β1. Integrin modulator 1 increases cell adhesion mediated by α4β1 integrin, with an EC50 of 12.9 nM[1]. Integrin modulator 1 (2-10 μg/mL; 30 min) significantly increases Jurkat E6.1 cell adhesion[1].Integrin modulator 1 (1-100 nM; 1 h) strongly and significantly increases ERK1/2 phosphorylation in Jurkat E6.1 cells[1].Integrin modulator 1 (1 nM-10 μM; 30 min) significantly increases the binding of HUTS-21 antibody to Jurkat E6.1 cells in a concentration-dependent manner[1]. [1]. Baiula M, et, al. New β-Lactam Derivatives Modulate Cell Adhesion and Signaling Mediated by RGD-Binding and Leukocyte Integrins. J Med Chem. 2016 Nov 10;59(21):9721-9742.

NLRP3-IN-8 (compound 27), an orally active NLRP3 inflammasome inhibitor, directly binds to its target with an IC50 of 1.23 μM for IL-1β inhibition. It demonstrates robust metabolic stability in liver microsomes (t1/2 = 138.63 min) and exhibits minimal toxicity (against L02: IC50 > 100 μM) [1].

BMS-665053 is a corticotropin-releasing factor-1 (CRF1) receptor antagonist (IC50 = 1.0 nM). BMS-665053)11 is a potent inhibitor of CRF-stimulated cyclic adenosine monophosphate (cAMP) production in human Y-79 retinoblastoma cells (IC50 = 4.9 nM). In addi

Adrenomedullin (13-52) is a truncated form of adrenomedullin (1-52) . It induces nitric oxide-dependent relaxation of and inhibits release of angiotensin II and endothelin-1 from isolated rat aorta. In vivo, adrenomedullin (13-52) decreases mean arterial pressure (MAP) in spontaneously and renal hypertensive rats in a dose-dependent manner. Adrenomedullin (13-52) (10-3,000 ng per animal) reverses increases in lobar arterial pressure induced by U-46619 in a dose-dependent manner in cats but has no effect on basal lobar arterial pressure or systemic arterial pressure. It also potentiates inflammatory edema and neutrophil accumulation in rats.

Sarpogrelate (MCI-9042) is a new, orally active, specific 5-HT2 receptor antagonist. sarpogrelate increases platelet aggregation, has a haemostatic effect and can be used in the study of berghett's disease.