DLin-M-K-DMA (DLin-M-C2-DMA) is a cationic lipid that can be used in the construction of biological delivery vectors[1].
Isradipine-d6 is the deuterium labeled Isradipine[1]. Isradipine (PN 200-110) is an orally active L-type calcium channel blocker. Isradipine, as a powerful peripheral vasodilator, is a dihydropyridine calcium antagonist with selective actions on the heart as well as the peripheral circulation. Isradipine is a potentially viable neuroprotective agent for Parkinson's disease[2][3][4].
M1/M4 muscarinic agonist 3 (compound 44) is a muscarinic mAChR M1/M4 agonist with EC50s of 31 nM and 9.3 nM, respectively[1].
RPR-260243 is a novel activator of HERG; modifies HERG currents inhibited by dofetilide (IC50 = 58 nM); little effect on HERG current amplitude and no significant effects on steady-state activation parameters or on channel inactivation processes.IC50 value: Target: HERG activatorRPR260243 displayed no activator-like effects on other voltage-dependent ion channels, including the closely related erg3 K+ channel. RPR260243 enhanced the delayed rectifier current in guinea pig myocytes but, when administered alone, had little effect on action potential parameters in these cells. However, RPR260243 completely reversed the action potential-prolonging effects of dofetilide in this preparation. Using the Langendorff heart method, we found that 5 μM RPR260243 increased T-wave amplitude, prolonged the PR interval, and shortened the QT interval. We believe RPR260243 represents the first known HERG channel activator and that the drug works primarily by inhibiting channel closure, leading to a persistent HERG channel current upon repolarization.
12-Acetoxyabietic acid is a compound isolated from ponderosa pine oleoresin[1].
Spautin-1 is a specific and potent autophagy inhibitor-1.
ASP7657 (ASP-7657) is a potent, selective, orally active prostaglandin EP4 receptor antagonist with Ki values of 6.02 nM and 2.21 nM for rat and human EP4 receptors, resepctively; potently inhibits the PGE2-induced cAMP increase in CHO cells expressing rat EP4 receptors and human lymphoblastoid T (Jurkat) cells, with IC50 values of 0.86 nM and 0.29 nM, respectively; does not inhibit the PGE2-induced intracellular calcium increase in HEK293 cells expressing rat EP1 and EP3 receptors, or cAMP increase in CHO cells expressing rat EP2 receptors; dose-dependently inhibits the PGE2-mediated inhibition of LPS-induced TNF-α release from rat whole blood culture, attenuates albuminuria in type 2 diabetic mice at dose of 0.1 mg/kg. Diabetes Phase 1 Discontinued
Torilin is a sesquiterpene with antimicrobial, anticancer, and anti-inflammatory properties. Torilin inhibits LPS-induced NO release, as well as inhibiting iNOS, PGE2, COX-2, NF-α, IL-1β, IL-6, and GM-CSF. Torilin suppresses NF-kB and AP-1 translocation, inhibits TAK1 kinase activation. Subsequently results suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-κBα degradation, p65/p50 activation, and translocation[1].
Tagraxofusp (SL-401) is a potent IL-3 receptor inhibitor to inhibits plasmacytoid dendritic cells (pDCs) growth in multiple myeloma (MM) bone marrow (BM) microenvironment. Tagraxofusp has synergistic effect with Bortezomib (HY-10227) and Pomalidomide (HY-10984) to suppress multiple myeloma (MM)[1].
ENS-163 phosphate is a selective muscarinic M1 receptor agonist.
Dodecylamine-d25 is the deuterium labeled Dodecylamine[1].
MPEP hydrochloride is a potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype with IC50 of 36 nM.IC50 Value: 36 nMTarget: mGluRin vitro: MPEP has no appreciable agonist or antagonist activity at the closely related recombinant human mGlu1b receptor expressed in CHO-K1 cells or a purinoreceptor endogenously expressed in L(tk-) cells up to concentrations of 100 μM. Furthermore, MPEP shows no appreciable agonist or antagonist activity in cAMP accumulation or [35S]-GTPγS binding assays at the recombinant human group II and III metabotropic receptors (human mGlu2, -3, -4a, -6, -7b, -8a) as well as the human NMDA (NMDAR1A/2A, -1A/2B), rat AMPA (GluR3) and human kainate (GluR6) receptor subtypes. In slices of rat neonatal hippocampus, striatum, and cortex but not cerebellum, MPEP inhibits DHPG-stimulated PI hydrolysis with IC50 of 8.0 nM, 20.5 nM, and 17.9 nM, respectively. MPEP positively modulates the hmGluR4 in a recombinant expression system, and the effect of MPEP is fully dependent on the activation of the orthosteric agonist L-AP4.in vivo: MPEP (1-30 mg/kg) induces anxiolytic-like effects in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice. MPEP (1-20 mg/kg) shortens the immobility time in a tail suspension test in mice, but it is inactive in the behavioural despair test in rats. MPEP has no effect on locomotor activity or motor coordination. MPEP significantly reduces fmr1 but not wild-type center square entries and duration. In open field tests, MPEP reduces fmr1tm1Cgr center field behavior to one indistinguishable from wild-type. MPEP produces a significant reduction of total locomotor activity in three of four groups tested, at both 10 mg/kg and 30 mg/kg.
BI-9321 trihydrochloride is a potent, selective and cellular active nuclear receptor-binding SET domain 3 (NSD3)-PWWP1 domain antagonist with a Kd value of 166 nM. BI-9321 trihydrochloride is inactive against NSD2-PWWP1 and NSD3-PWWP2. BI-9321 trihydrochloride specifically disrupts histone interactions of the NSD3-PWWP1 domain with an IC50 of 1.2 μM in U2OS cells[1].
Ro-24-0238 is an antagonist of platelet activating factor (PAF) and inhibitor of thromboxane synthesis, used for lessening the inflammation and damage resulting from a local release of PAF.
RIPK2-IN-1 (compound 18f) is a potent RIPK2 inhibitor with an IC50 of 51 nM. RIPK2-IN-1 inhibits ALK2 with an IC50 of 5 nM. RIPK2-IN-1 has an IC50 of 390 nM on RIPK2/NOD2 in cell assay[1].
JAK kinase-IN-1 (Example 1) is a JAK inhibitor. JAK kinase-IN-1 inhibits TYK2, JAK1, JAK2 and JAK3 with IC50 values of 4.2 nM, 32 nM, 27 nM, 3473 nM respectively[1].
Isorhamnetin 3,7-di-O-β-D-glucopyranoside, a major flavonoid compound, is metabolized in vivo by intestinal bacteria to isorhamnetin and that isorhamnetin plays an important role as an antioxidant[1].
Fosinopril-d5 sodium (SQ28555-d5 sodium) is the deuterium labeled Fosinopril sodium. Fosinopril Sodium is the ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor, used for the treatment of hypertension and some types of chronic heart failure[1][2].
MtTMPK-IN-4 (compound 2), a para-piperidine, is a potent mycobacterium tuberculosis thymidylate kinase (MtTMPK) inhibitor with an IC50 of 6.1 μM. MtTMPK-IN-4 is a potent tyrosinase inhibitor. MtTMPK-IN-4 is a potent antibacterial agent[1][2].
Casein kinase 1δ-IN-14 (compound 481) is a casein kinase inhibitor that can be used to study neurodegenerative diseases such as Alzheimer's disease[1].
KRAS inhibitor-14 (compound 3-22) is a potent KRAS G12C inhibitor with an IC50 of 0.249 µM. KRAS inhibitor-14 shows p-ERK inhibition activities with IC50s of 1.12, >33.3 µM in MIA PaCA-2, A549 cells, respectively. KRAS inhibitor-14 has the potential for the research of pancreatic, colorectal, and lung cancers[1].
Boc-NH-PEG8-CH2CH2NH2 is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].
SGX-523 is a selective Met inhibitor with IC50 of 4 nM, no activity to BRAFV599E, c-Raf, Abl and p38α.IC50 value: 4 nM [1]Target: Metin vitro: SGX-523 belongs to the class of c-Met/hepatocyte growth factor receptor (HGFR) tyrosine kinase inhibitors. SGX-523 stabilizes MET in a unique inactive conformation that is inaccessible to other protein kinases, suggesting an explanation for its selectivity. SGX523 potently inhibits the purified MET catalytic domain but not the closely related receptor tyrosine kinase RON. SGX523 indicates ATP-competitive inhibition with higher apparent affinity for the less active, unphosphorylated form of MET [MET-KD(0P), with a Ki of 2.7 nM] versus the more active phospho-enzyme [MET-KD(3P), with a Ki of 23 nM], a phenomenon consistent with preferential binding to an inactive enzyme conformation. SGX523 inhibits MET-mediated signaling, cell proliferation and cell migration at nanomolar concentrations but had no effect on signaling dependent on other protein kinases, including the closely related RON, even at micromolar concentrations [1].in vivo: SGX523 significantly retards the growth of preestablished GTL16 tumors when administered orally at doses of ≥10 mg/kg twice daily. SGX523 potently inhibits U87MG tumor growth; at 30 mg/kg dosed twice daily, SGX523 leads to clear regression of U87MG tumors. SGX523, dosed twice daily at 30 mg/kg, also retards the growth of H441 tumors with concomitant reduction in tumor MET autophosphorylation levels. SGX523 inhibition of MET in vivo is associated with the dose-dependent inhibition of growth of tumor xenografts derived from human glioblastoma, lung and gastric cancers, confirming the dependence of these tumors on MET catalytic activity [1].
Vapiprost hydrochloride is a thromboxane A2 receptor antagonist. Vapiprost inhibits the aggregation and ATP release stimulated with U-46619, collagen or arachidonic acid (AA) at an IC50 of less than 2.1×10-8 M[1].
Cyclo(L-Phe-L-Pro), isolated from Pseudomonas fluorescens and Pseudomonas alcaligenes cell-free culture supernatants is an antifungal cyclic dipeptide[1]. Cyclo(L-Phe-L-Pro) inhibits IFN-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation[2]. Cyclo(L-Phe-L-Pro) exhibits free-radical scavenging activity with the IC50 of 24 µM in the DPPH assay[3].
Benzyl-PEG9-THP is a PEG-based PROTAC linker that can be used in the synthesis of PROTACs[1].
Theodrenaline hydrochloride is a cardiac stimulant, also acts as an anti-hypotensive agent together with Cafedrine.
PI3Kδ-IN-11 is a highly potent and selective PI3Kδ inhibitor with IC50 value of 27.5 nM. PI3Kδ-IN-11 dose-dependently blocks the activity of PI3K/Akt pathway. PI3Kδ-IN-11 can be used for researching B or T cell-related malignancies[1].
ML314 is a potent molecule agonist of NTR1 (EC50 = 1.9 μM); showed good selectivity against NTR2 and GPR35, but did not stimulate Ca2+ mobilization.IC50 value: 1.9 uM (EC50) [1]Target: NTR1 agonistMedicinal chemistry optimization of MLS-0233108 led to ML314, the most potent molecule in this second series that exhibited full agonist behavior (100 %) on NTR1 (EC50 = 1.9 μM). ML314 showed good selectivity against NTR2 and GPR35, but did not stimulate Ca2+ mobilization. ML314 is potentially a biased agonist operating via the β-arrestin pathway rather than the traditional Gq coupled pathway. Signaling mediated by β-arrestin has distinct biochemical and functional consequences that may lead to physiological advantages as described below. This probe report describes the discovery and properties of ML301 and summarizes the HTS and follow-up campaign, which identified ML314.
Zaurategrast ethyl ester sulfate (CDP323 sulfate), the ethyl ester prodrug of CT7758[1], is a α4β1/α4β7 integrin antagonist used for the treatment of inflammatory and autoimmune disorders[2].