Schisandrol B is one of its major active constituents of traditional hepato-protective Chinese medicine, Schisandra sphenanthera.IC50 value:Target:in vitro: SolB pretreatment significantly attenuated the increases in alanine aminotransferase and aspartate aminotransferase activity, and prevented elevated hepatic malondialdehyde formation and the depletion of mitochondrial glutathione (GSH) in a dose-dependent manner. SolB also dramatically altered APAP metabolic activation by inhibiting the activities of CYP2E1 and CYP3A11, which was evidenced by significant inhibition of the formation of the oxidized APAP metabolite NAPQI-GSH [1]. SolB abrogated APAP-induced activation of p53 and p21, and increased expression of liver regeneration and antiapoptotic-related proteins such as cyclin D1 (CCND1), PCNA, and BCL-2.
Gemigliptin tartrate (LC15-0444 tartrate) is a highly selective, reversible and competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, with an IC50 of 10.3 nM for human recombinant DPP-4. Gemigliptin tartrate exhibits potent anti-glycation properties. Gemigliptin tartrate can be used for the research of advanced glycation end products (AGE)-related diabetic complications[1][2].
Conglobatin (FW-04-806), a macrolide dilactone, is isolated from the culture of Streptomyces conglobatus. Conglobatin is an orally active Hsp90 inhibitor. Conglobatin can bind to the N-terminal domain of Hsp90 and disrupt Hsp90-Cdc37 complex formation. Conglobatin induces apoptosis in human breast cancer cells and esophageal squamous cell carcinoma cells, and exhibits antitumor activity in vivo[1][2][3].
DHODH-IN-12 (Compound 12b) is a Leflunomide derivative and a weak dihydroorotate dehydrogenase (DHODH) inhibitor with a pKa of 5.07[1].
Abelacimab (MAA868) is a fully human IgG1 monoclonal antibody that binds with high affinity to the catalytic structural domain of FXI and locks it in the zymogen conformation, thereby preventing its activation by FXIIa or thrombin. Abelacimab can be used in thromboembolic disease studies[1][2].
GEM-5 is a gemcitabine-based conjugate containing a HIF-1α inhibitor (YC-1) (IC50=30 nM). GEM-5 can significantly down-regulate the expression of HIF-1α and up-regulate the expression of tumor suppressor p53. GEM-5 induces the apoptosis of A2780 cells and inhibits tumor growth[1].
ALDH1A1-IN-3 (compound 57) is an excellent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitor with an IC50 value of 0.379 μM. ALDH1A1-IN-3 can effectively improve glucose consumption in HepG2 cells. ALDH1A1-IN-3 can be used for researching glucose metabolism improvement[1].
HIF-PHD-IN-2 (compound 25) is a potent PHD inhibitor with IC50s of <100 nM for PHD1, PHD2 and PHD3, respectively[1].
Papain inhibitor (Glycylglycyl-L-tyrosyl-L-arginine) acts as an effective competitive inhibitor to papain, with a Ki of 9 μM at pH 6.2[1].
Methyl orsellinate is a phytotoxic compound with antifungal activities. Methyl orsellinate is a 5-lipoxygenase inhibitor with an IC50 value of 59.6 μM. Methyl orsellinate can be used for fungal infection research[1][2].
Arg-Val-(Nle-p-nitro)-Phe-Glu-Ala-Nle-NH2 is a fluorogenic substrate of HIV-1 protease. Arg-Val-(Nle-p-nitro)-Phe-Glu-Ala-Nle-NH2 can be used to test HIV-1 protease activity[1].
H-Tyr-Tyr-OH (L-Tyrosyl-L-tyrosine) is an antihypertensive peptide. H-Tyr-Tyr-OH inhibits angiotensin I-converting enzyme (ACE) with an IC50 value of 0.028 mg/mL. H-Tyr-Tyr-OH can be used for the research of high blood pressure[1][2].
FTI-2148 diTFA is a RAS C-terminal mimetic dual farnesyl transferase (FT-1) and geranylgeranyl transferase-1 (GGT-1) inhibitor with IC50s of 1.4 nM and 1.7 μM, respectively[1].
6BrCaQ is a potent mitochondrial heat shock protein TRAP1 inhibitor, with antiproliferative activity. 6BrCaQ can be used in the synthesis of 6BrCaQ-TPP conjugates[1].
MLS-0437605 is a specific inhibitor of dual-specificity phosphatase 3 (DUSP3) with IC50 of 3.7 uM, 7-fold selectivity over USP22 and >4-fold selectivity over other 10 PTPs (HePTP, TCPTP, PTP1B, etc.); specifically inhibits collagen- and C-type lectin-like receptor 2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells.
Arg-Arg-AMC is a highly selective substrate of Cathepsin B. Arg-Arg-AMC can be used to cathepsin B activity assay in cancer cells, while cathepsin B is assocaited with cell invasive and metastatic phenotype in numerous types of cancer[1].
CYP1B1-IN-5 (Compound 6q) is a potent and selective cytochrome P450 1B1 (CYP1B1) inhibitor with an IC50 of 4.7 nM[1].
VU0155069 (CAY10593), compound 69, is a selective phospholipase D1 (PLD1) inhibitor with an IC50 value of 46 nM in vitro[1]. VU0155069 (CAY10593) strongly inhibits the invasive migration of several cancer cell lines in transwell assays[2].
Benzenesulphonamide (compound 1) is a potent carbonic anhydrase inhibitor. Benzenesulphonamide shows CA II inhibitory activity[1].
SCD1/5-IN-1 (Compound 10) is a SCD1/5 inhibitor. SCD1/5-IN-1 can be used for research of neurological disease[1].
FXIa-IN-1 (compound EP-7041) is a potent β-lactam covalent heparin-derived factor XIa (fXIa) inhibitor[1].
BRD2889 is an analog of the alkaloid piperlongumine. BRD2889 is a robust modulator of the GSTP1-ISCU axis in pulmonary hypertension (PH)[1].
WNK1-IN-1 is a selective inhibitor of WNK1 with an IC50 value of 1.6 μM. WNK1-IN-1 inhibits OSR1 phosphorylation with an IC50 value of 4.3 μM. WNK1-IN-1 can be used for the research of blood pressure regulation and cancer[1].
Enoxaparin (PK 10169), a low-molecular-weight heparin (LMWH) derivative. Enoxaparin exerts anticoagulant activity through antithrombin III, an endogenous inhibitor of factor Xa and thrombin IIa. Enoxaparin protect the rat hippocampus against TBI (traumatic brain injury) via antioxidant and anti-inflammatory properties. Enoxaparin can be used for the research of deep vein thrombosis (DVT), pulmonary embolism, TBI and COVID-19[1][2][3].
Vildagliptin (LAF-237; NVP-LAF 237) inhibits DPP-4 with IC50 of 2.3 nM.IC50 Value: 2.3 nM[1]Target: DPP-4in vitro: Vildagliptin is an N-substituted glycyl-2-cyanopyrrolidine (figure 2). It is a potent competitive and reversible inhibitor of human and rodent DPP-4 in vitro, with a median inhibitory concentration (IC50) ~2-3 nmol/L. Importantly, vildagliptin inhibits DPP-4 with high specificity relative to other similar peptidases where its IC50 exceeds 200 mol/L [1].in vivo: Compared to age-, gender-, BMI-matched subjects with normal renal function, the mean AUC of vildagliptin after 14 days in patients with mild, moderate, and severe RI increased by 40%, 71%, and 100%, respectively [2]. The treatment was effective in modulating stress in pancreatic tissue, both by reducing levels of stress markers as well as by increasing activity of SOD and catalase. After analyzing the pancreatic histology, we found that vildagliptin was also able to preserve islets and pancreatic β-cells, especially at the concentration of 5 mg/kg [3].Clinical trial: FDA approved drug.
H-Trp-Phe-OH is a dipeptide consisting of tryptophan and phenylalanine (Trp-Phe). H-Trp-Phe-OH is also an antihypertensive peptide with inhibitory activity on angiotensin-converting enzyme (ACE), dose-dependently increases NO levels, and decreases endothelin-1 (ET-1) levels. H-Trp-Phe-OH (2 mg/kg; subcutaneous injection; 6 injections over 3 days) causes an increase in ovarian weight in female mice[1][2].
WWL154, an analog of JZL184 that maintains the SH-reactive p-nitrophenyl carbamate group, is a FAAH-4 inhibitor[1].
h-NTPDase-IN-5 (compound 3b) is a pan-inhibitor of NTPDase with IC50s of 1.10 μM (h-NTPDase1), 44.73 μM (h-NTPDase2), 26.14 μM (h-NTPDase3), 0.32 μM (h- NTPDase8).
AZD7545 is a novel, selective small-molecule inhibitor of PDHK2 (PDH kinase2) with an IC50 of 36.8 nM and 6.4 nM for PDHK1 and PDHK2 respectively.IC50 Value: 36.8 nM (PDHK1); 6.4 nM (PDHK2) [1]Target: PDHK1/2in vitro: The IC50 values for inhibition of PDHK2 and PDHK1 by AZD7545 were 6.4 ± 2.2 nM (n = 6) and 36.8 ± 18 nM (n = 3) respectively. Other compounds in this series inhibited both PDHK1 and PDHK2 and a consistent trend of reduced potency (5-15-fold) towards PDHK1, as compared with PDHK2, was observed. In contrast, AZD7545 and related compounds failed to inhibit PDHK4 and paradoxically, at higher concentrations (>10 nM), AZD7545 stimulated PDHK4 activity [1]. In the presence of PDHK2, AZD7545 increased PDH activity with an EC(50) value of 5.2 nM. In rat hepatocytes, the rate of pyruvate oxidation was stimulated 2-fold (EC(50) 105 nM) [2].in vivo: A single dose of AZD7545 to Wistar rats increased the proportion of liver PDH in its active, dephosphorylated form in a dose-related manner from 24.7 to 70.3% at 30 mg/kg; and in skeletal muscle from 21.1 to 53.3%. A single dose of 10 mg/kg also significantly elevated muscle PDH activity in obese Zucker (fa/fa) rats. Obese, insulin-resistant, Zucker rats show elevated postprandial glucose levels compared with their lean counterparts (8.7 versus 6.1 mM at 12 weeks old). AZD7545 (10 mg/kg) twice daily for 7 days markedly improved the 24-h glucose profile, by eliminating the postprandial elevation in blood glucose [2]. An interestingobservation is that administration of maximally effective doses of AZD7545 and related compounds to rats results in the near-complete activation of PDH activity in liver, where PDHK2 is the major isoenzyme, while only partial activation of PDH activity is achieved in skeletal muscle and heart, tissues which express high levels of PDHK4. For example, following administration of a maximally effective dose of compound K (30 mg/kg) the percentage of PDH present in the active (dephosphorylated) state in liver is elevated from 35.3 ± 4.0% to 90.2 ± 2.2% while in skeletal muscle and heart PDH activity plateaus at 64.3 ± 2.3% and 61.8 ± 4.3% respectively. Further evidence for a link between in vitro isoenzyme selectivity and in vivo activity comes from the observation that in fasted rats the ability of AZD7545 toelevate PDH activity in liver is intact, while the activation of skeletal muscle PDH activity in response to the compound is severely blunted [1].
SQ 32602 is a cathepsin E inhibitor.