k 41

K 41 is a polycyclic polyether antibiotic from Streptomyces hygroscopicus.

PI3K-IN-41 (compound 2), a photocaged PI3K inhibitor (IC50=18.92 nM) with anticancer properties, demonstrates potent PI3K inhibition following UV light irradiation and has been shown to enhance antitumor effects [1]. This compound has potential for use in precisely controlled cancer therapeutics.

MK 410 is an indomethacin analogue and anti-inflammatory agent that induces changes in the immune system by inhibiting plasma neutral protease activity.

K 41498 is a selective peptide antagonist targeting both corticotropin-releasing factor receptor 2α (CRF2α) and CRF2β, demonstrating high affinity with Kis of 0.66 and 0.62 nM, respectively, in HEK293 cells expressing these human receptors. Its selectivity is evident as it exhibits a significantly reduced affinity for CRF1 receptor (Ki = 425 nM in HEK293 cells expressing the human CRF1 receptor). Additionally, K 41498, when administered intravenously at 1.84 µg/animal, effectively mitigates urocortin-induced hypotension in rats. Furthermore, its intrathecal delivery ranging from 0.075 to 0.5 µmol/animal significantly lowers the mechanical paw withdrawal threshold in a rat model, indicating its potential utility in managing nociception triggered by complete Freund's adjuvant.

K41498 acetate, an analogues of antisauvagine-30 (aSvg-30), inhibits sauvagine-stimulated cAMP accumulation in hCRF2α- and hCRF2β-expressing cells. K41498 acetate is a potent and highly selective antagonist CRF2 receptor with Ki values of 0.66 nM, 0.62 nM and 425 nM for human CRF2α, CRF2β and CRF1 receptors respectively.

DK419 is an orally active inhibitor of Wnt/β-catenin signaling, with an IC50 of 0.19 μM. DK419 decreases protein lelvels of Axin2, β-catenin, c-Myc, Cyclin D1 and Survivin.It also induces production of pAMPK.

TAK-418 is a selective and orally active inhibitor of LSD1/KDM1A enzyme with an IC50 of 2.9 nM. TAK-418 unlocks abnormal epigenetic mechanisms and improves autism symptoms in models of neurodevelopmental disorders.

LRK-4189 is an orally active, selective PIP4K2C PROTAC degrader with a DC50 <500 nM in MOLT-4 cells. It induces endogenous apoptosis and activates the interferon signaling pathway, exhibiting antitumor activity against microsatellite stable (MSS) colorectal cancer (CRC) cells.

STK414603 is a heterocyclic acetamide derivative with potential analgesic, anti-inflammatory, and antimicrobial activities.

VK4-116 (Compound 19) is a selective dopamine D3 receptor (D3R) antagonist with a Ki of 6.84 nM. It significantly inhibits oxycodone-induced hyperactivity and locomotor sensitization in mouse models. Additionally, VK4-116 pretreatment suppresses the acquisition of oxycodone-induced conditioned place preference (CPP) in rat models.

UK-414,495 is a potent, selective inhibitor of the neutral endopeptidase, the enzyme normally serves to break down the neuropeptide VIP.

GSK4112 (SR6452) is a Rev-erbα agonist with an EC50 of 0.4 μM and serves as a small molecule chemical probe for studying the cell biology of the nuclear heme receptor Rev-erbα.

MK-4101, an effective inhibitor of the Hedgehog pathway, has anti-tumor activity through the induction of extensive apoptosis and inhibition of proliferation in tumor cells.

Vicriviroc, also known as MK4176 is a CCR5 antagonist.

K41498 TFA, an analog of antisauvagine-30 (aSvg-30), is a potent and highly selective antagonist of CRF2 receptors, exhibiting K i values of 0.66 nM, 0.62 nM, and 425 nM for human CRF 2α, CRF 2β, and CRF 1 receptors, respectively. This compound effectively inhibits sauvagine-stimulated cAMP accumulation in cells expressing hCRF 2α and hCRF 2β. It is utilized in studies investigating hypotension [1].

Sotrovimab (VIR 7831) is a monoclonal antibody against the SARS-CoV-2 virus that causes COVID-19. It has antiviral activity, induces serum neutralization of BQ.1 and antibody-dependent cytotoxicity, and may be used to study viral infections.

MK-4166 is a humanized IgG1 agonistic monoclonal antibody targeting GITR. It is capable of enhancing the proliferation of both naive T lymphocytes and tumor-infiltrating T lymphocytes.

Potent and highly selective CRF2 receptor antagonist (Ki values are 0.66, 0.62 and 425 nM for human CRF2α, CRF2β and CRF1 receptors respectively). Inhibits sauvagine-stimulated cAMP accumulation in hCRF2α- and hCRF2β-expressing cells. In rats in vivo, blo

Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg/ml) and Gram-negative bacteria (MICs = 136-200 µg/ml), as well as yeasts (MICs = 10-20 µg/ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16/BL6 mouse model of melanoma when administered at a dose of 25 mg/kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg/kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg/ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg/kg.3Ajoene (25 mg/kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)

Relacatib (SB-462795) is a novel, potent, and orally active inhibitor of human cathepsins K, L, and V, exhibiting high affinity with Ki values of 41 pM, 68 pM, and 53 pM, respectively. It effectively inhibits endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50 values of 45 nM and 70 nM, respectively. In vitro studies confirm its inhibitory effect on bone resorption in human tissue, and in vivo studies on cynomolgus monkeys validate its efficacy in reducing bone resorption.

Enpp-1-IN-12 (compound 43), an orally active and potent inhibitor of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) with a K_i of 41 nM, exhibits anti-tumor activity [1].

α-Helical CRF(9-41) TFA acts as a competitive antagonist for the CRF2 receptor, with a binding constant (K B) of approximately 100 nM, and serves as a partial agonist for the CRF1 receptor, exhibiting a half-maximal effective concentration (EC 50) of 140 nM [1] [2].

Stressin I (Cyclo(31-34)[DPhe12, Nle21, 38, Glu31, Lys34]Ac-hCRF(4-41)) TFA, with a K i of 1.7 nM, is a potent and selective agonist of the CRF1 receptor that elevates adrenocorticotropic hormone (ACTH) levels in rats [1].

CVN293 is a selective inhibitor of the potassium channel KCNK13, with the advantages of brain permeability and oral bioavailability. It inhibits the production of the pro-inflammatory cytokine IL-1β induced by NLRP3 in microglia and can be used for research into neurodegenerative diseases.