k 4

K-Ras G12C-IN-4, is a potent Covalent Inhibitor of KRASG12C..

Antibiotic K 4 is an inhibitor of angiotensin I converting enzyme produced by Actinomadura spiculosospora.

K-Ras ligand-Linker Conjugate 4 is a chemical compound combining a K-Ras recruiting ligand with a PROTAC linker, responsible for recruiting E3 ligases such as VHL, CRBN, MDM2, and IAP. It has the potential to be used in synthesizing PROTAC K-Ras Degrader-1, which shows a degradation efficacy of ≥70% in SW1573 cells[1].

c(phg-isoDGR-(NMe)k) TFA is a potent and selective α5β1-integrin ligand (IC50: 2.9 nM).

Vitamin K4 (Menadiol Diacetate) is a vitamin medicine for the treatment of blood coagulation disorders that caused by the lack of VK4.

TAK1 MAP4K2 inhibitor 1 is a potent dual inhibitor of TGFβ-activated kinase 1 (TAK1) and MAP4K2 [IC50s: 41.1 nM and 18.2 nM].

MAP4K4-IN-3 (Compound 17), a serine threonine protein kinase, may be a viable target for antidiabetic agents.

K4 peptide exhibits potent antimicrobial properties, effectively targeting both Gram-positive and Gram-negative bacteria, particularly pathogenic strains like Staphylococcus aureus and Marine Vibrio species [1].

PI3Kγ inhibitor 4 is a selective, potent, orally active PI3Kγ inhibitor (IC50: 40 nM). PI3Kγ inhibitor 4 is ~7-fold more selective for PI3Kγ than the α subtype, 43-fold more selective than the β subtype and 18-fold more selective than the δ subtype. inflammation.

Vitamin K1-d4 is a deuterated compound of Vitamin K1. Vitamin K1 has a CAS number of 84-80-0. Vitamin K1 (Phylloquinone) is a naturally-occurring vitamin. Vitamin K1 is essential for blood clotting, bone and vascular metabolism.

(S)-PI3Kα-IN-4, a potent inhibitor of PI3Kα with an IC50 of 2.3 nM, demonstrates 38.3-, 4.25-, and 4.93-fold selectivity over PI3Kβ, PI3Kδ, and PI3Kγ, respectively, and is suitable for cancer research[1]. (S)-PI3Kα-IN-4 (compound 11) is a quinazolin-4(3H)-one derivative with 2-substituted-N-methylpropanamide substitution[1].

PI3K mTOR Inhibitor-4 is an orally active pan-I PI3K mTOR enzyme inhibitor, acting on PI3Kα (IC50: 0.63 nM), PI3Kγ (IC50: 22 nM), PI3Kδ (IC50: 9.2 nM), and mTOR (IC50: 13.85 nM). PI3K mTOR Inhibitor-4 can be used to study cancer.

M4K2234 (compound 26b), an ALK2 inhibitor, demonstrates selective inhibition of ALK2 and ALK5 with IC50 values of 5 nM and 2144 nM, respectively. Serving as a chemical probe for ALK1 and ALK2 protein kinases, M4K2234 holds potential for cancer research applications [1].

CHMFL-PI4K-127 (compound 15g) is a highly selective inhibitor of PfPI4K (Plasmodium falciparum PI4K kinase) with oral activity (IC50=0.9 nM) and exhibits strong inhibitory activity against Plasmodium falciparum 3D7 (EC50=25.1 nM), demonstrating significant anti-malaria effects.

PI5P4K-β-IN-1 (compound vs1) is a potent PI5P4K-β inhibitor with an IC50 of 0.80 μM [1].

PI5P4Kα-IN-1 (Compound 13) is a phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) inhibitor with IC50 values of 2 μM for PI5P4Kα and 9.4 μM for PI5P4Kβ, potentially applicable in cancer, metabolic, and immunological disorder studies [1].

TNIK&MAP4K4-IN-1 (compound A-39) is a potent dual inhibitor of TNIK and MAP4K4 HGK, with IC50 values of 1.29 nM and <10 nM, respectively, in human hepatic stellate cell LX-2, and is applicable in cancer and fibrosis inhibition [1].

4N1K peptide, a biologically active peptide derived from thrombospondins (KRFYVVMWKK), exhibits anti-cancer activities in various cancers.

PI5P4K-β-IN-2 (compound d5) is a potent inhibitor of the PI5P4K-β enzyme with an IC50 value of 0.35 μM and exhibits antitumor activity.

PIP4K-IN-a131 is a selective inhibitor of PIP4K lipid kinases, demonstrating IC50 values of 1.9 μM for PIP4K2A and 0.6 μM for PIP4Ks. It exhibits cancer-selective lethality by simultaneously blocking the lipid kinase PIP4Ks and mitotic pathways.

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

M4K2163 dihydrochloride, a potent and selective activin receptor-like kinase-2 (ALK2) inhibitor that is permeable to the blood-brain barrier (BBB), has an IC50 of 19 nM. This compound is useful in diffuse intrinsic pontine glioma (DIPG) research [1] [2].

PI5P4Kγ-IN-1 (compound 2), a selective PI5P4Kγ inhibitor, facilitates mTORC1 signaling in MCF-7 breast cancer cells and aids in further characterization of PI5P4Kγ within these cells [1].

CDK8-IN-4k is a potent and highly selective CDK8 inhibitor, with no apparent potential for time-dependent CYP3A4 inhibition.

8K13-hz35-STING-D4-1203 is an ADC (antibody-drug conjugate) linker compound.

PF-04753299 is a potent and selective inhibitor of UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC), demonstrating bactericidal effects against gonococcal isolates and exhibiting inhibitory activity against E. coli, P. aeruginosa, and K. pneumoniae, with minimum inhibitory concentration (MIC) 90 values of 2 μg ml, 4 μg ml, and 16 μg ml, respectively. This compound is utilized in researching gram-negative bacterial infections [1].

1-((3R,4S)-3-hydroxy-2,2-dimethyl-6-(phenylsulfonyl)chroman-4-yl)pyrrolidin-2-one is an isomer of Rilmakalim, a potassium channel opener (PCO), which can activate ATP-sensitive K+ channels in the heart or other tissues

4-Aminobenzamidine dihydrochloride (p-Aminobenzamidine dihydrochloride) is a strong trypsin inhibitor and a relatively weak inhibitor of urokinase type plasminogen activator (uPA) (K i =82 μM). 4-Aminobenzamidine can inhibit growth of a human prostate tumor in SCID mice [1] [2].

Menaquinone-4 (Vitamin K2) is a vitamin K compound used as a hemostatic agent, and also as adjunctive therapy for the pain of osteoporosis.

1. 2,5-Dihydroxyacetophenone (Quinacetophenone) possess anti-anxiety, and neuroprotective qualities. 2. 2,5-Dihydroxyacetophenone (Quinacetophenone) reatment can induce a sustained activation of JNK, ERK1 2, and p38 MAPKs, it also can potentiate the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. 3. 2,5-Dihydroxyacetophenone (Quinacetophenone) has anti-inflammatory activity in activated macrophages, raising the possibility that this compound has a therapeutic potential for inflammatory conditions. 4. 2,5-Dihydroxyacetophenone (Quinacetophenone) is an uncompetitive inhibitor of murine tyrosinase (K(I) 0.28mm), it strongly inhibits both melanogenesis and cellular tyrosinase activity in vitro in 3-isobutyl-1-methylxanthin-stimulated B16 mouse melanoma cells or in vivo in zebrafish and mouse models.

Proteinase K (Protease K) is a non-specific serine protease that can tolerate changes in SDS, urea, pH (4-12), salt concentration, and temperature. Proteinase K hydrolyzes a wide range of peptide bonds and is used for protein digestion.

Minamestane is a novel irreversible aromatase inhibitor.Minamestane induces time-dependent inhibition of human placental aromatase with a half-life of 4 minutes and a K of 59 nM.Minamestane has antitumor activity.

MK-571 sodium (L-660711 sodium salt) is a selective, orally active antagonist of the CysLT1 receptor. MK-571 sodium is a multidrug resistance protein-2 (ABCC2, Mrp2) inhibitor used to demonstrate the role of Mrp2 in the cellular efflux of drugs, xenobiotics, and their conjugates. MK-571 sodium can inhibit the synthesis of K-4′-O-GlcA (19.7 μM). MK571 dose-dependently inhibits the intracellular biosynthesis of all flavonol sulphates and glucuronides by Caco-2 cells. MK-571 sodium significantly inhibits phase-2 conjugation of kaempferol by cell-free extracts of Caco-2, and production of kaempferol-4′-O-glucuronide was competitively inhibited. In addition to inhibiting MRP2, MK571 is a potent inhibitor of enterocyte phase-2 conjugation.

Astemizole (Laridal) is a synthetic piperidinyl-benzimidazol derivative with antiallergic properties, acts as a reversible competitive inhibitor of histamine H1 receptors, with less anticholinergic effects compared to related agents. It is a long-acting, non-sedative antihistaminic used in the treatment of seasonal allergic rhinitis, asthma, allergic conjunctivitis, and chronic idiopathic urticaria.

VU0463271 (N-Cyclopropyl-N-(4-methyl-2-thiazolyl)-2-[(6-phenyl-3-pyridazinyl)thio]acetamide) is a potent and selective antagonist of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC50 of 61 nM and >100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels, and transporters.

K-Ras-IN-1, a K-Ras inhibitor, is characterized by its chemical formula C20H19ClN4O2S and is also known as N-[(1S)-3-cyclopropyl-1-[(6-fluoro-1H-benzimidazol-2-yl)sulfanyl]-2-oxo-1-(phenylmethyl)propyl]-4-fluorobenzenesulfonamide (compound [18, dashboard 819041] in brackets).

Betrixaban (PRT054021) is a non-vitamin K oral anticoagulant whose action is driven by the competitive and reversible inhibition of the factor Xa [1]. It was selected among all lead compounds due to its low hERG channel affinity while sustaining its factor Xa inhibition capacity [3]. Betrixaban, now developed by Portola Pharmaceuticals Inc., is prescribed as a venous thromboembolism (VTE) prophylactic for adult patients with moderate to severe restricted motility or with other risks for VTE [2]. VTE can be manifested as deep vein thrombosis or pulmonary embolism and it is a leading cause of preventable death in hospitalized patients [4].

Rabeprazole sodium (Habeprazole Sodium) is a 4-(3-methoxypropoxy)-3-methylpyridinyl derivative of timoprazole that is used in the therapy of stomach ulcers and Zollinger-Ellison syndrome. The drug inhibits H(+)-K(+)-exchanging ATPase which is found in gastric parietal cells.

Betrixaban maleate is a non-vitamin K oral anticoagulant whose action is driven by the competitive and reversible inhibition of the factor Xa.

7-Amino-4-methylcoumarin-3-acetic acid [7-Amino-4-methylcoumarin] is a more suitable substrate for enteropeptidase compared to GD(4)K-NA.

Nitisinone-13C6is intended for use as an internal standard for the quantification of nitisinone by GC- or LC-MS. Nitisinone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), which converts 4-hydroxyphenylpyruvate (HPPA) to homogentisate in the tyrosine catabolic pathway.1Nitisinone increases urinary levels of HPPA and 4-hydroxyphenyllactate (HPLA) in rats when administered at a dose of 10 mg/kg. Nitisinone (3 mg/kg) prevents the neonatal lethality of fumarylacetoacetate hydrolase (FAH) deficiency in mice when administered to pregnant dams.2It exhibits hepatoprotective effects inFAH-/-mice, such as prevention of increases in plasma levels of aspartate serine aminotransferase (AST) and conjugated bilirubin, when administration is continued following birth at a dose of 1 mg/kg. Nitisinone (100 μg) decreases urinary excretion of homogentisate and increases urinary excretion of HPPA, HPLA, and 4-hydroxyphenylacetate in a mouse model of alkaptonuria induced by ethylnitrosourea.3Formulations containing nitisinone have been used in the treatment of hereditary tyrosinemia type 1 (HT-1). 1.Ellis, M.K., Whitfield, A.C., Gowans, L.A., et al.Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dioneToxicol. Appl. Pharmacol.133(1)12-19(1995) 2.Grompe, M., Lindstedt, S., al-Dhalimy, M., et al.Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type INat. Genet.10(4)453-460(1995) 3.Suzuki, Y., Oda, K., Yoshikawa, Y., et al.A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuriaJ. Hum. Genet.44(2)79-84(1999)

PAR2 (1-6) amide is a synthetic peptide agonist of proteinase-activated receptor 2 (PAR2) that corresponds to residues 1-6 of the amino terminal tethered ligand sequence of human PAR2 and residues 37-42 of the full-length sequence.1It binds to NCTC 2544 cells expressing human PAR2 (Ki= 9.64 μM in a radioligand binding assay) and induces calcium mobilization in the same cells (EC50= 0.075 μM).2PAR2 (1-6) amide (100 μM) reduces colony formation of A549 lung cancer cells.1It induces superoxide production and degranulation in isolated human eosinophils when used at a concentration of 500 μM.3PAR2 (1-6) amide (5 μmol/kg) induces tear secretion in rats when used in combination with amastatin .4 1.Bohm, S.K., Kong, W., Bromme, D., et al.Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2Biochem. J.314(Pt 3)1009-1016(1996) 2.Kanke, T., Ishiwata, H., Kabeya, M., et al.Binding of a highly potent protease-activated receptor-2 (PAR2) activating peptide, [3H]2-furoyl-LIGRL-NH2, to human PAR2Br. J. Pharmacol.145(2)255-263(2005) 3.Miike, S., McWilliam, A.S., and Kita, H.Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2J. Immunol.167(11)6615-6622(2001) 4.Nishikawa, H., Kawai, K., Tanaka, M., et al.Protease-activated receptor-2 (PAR-2)-related peptides induce tear secretion in rats: Involvement of PAR-2 and non-PAR-2 mechanismsJ. Pharmacol. Exp. Ther.312(2)324-331(2005)

DSPE-PEG(2000)-amine is a PEGylated derivative of 1,2-distearoyl-sn-glycero-3-PE . It has been used in the synthesis of solid lipid and thermosensitive liposomal nanoparticles for the delivery of anticancer agents.1,2,3DSPE-PEG(2000)-amine has also been used in the synthesis of fluorescein isothiocyanate-loaded mesoporous silica nanoparticles for imaging applications.4It can be conjugated to a variety of functional molecules for improved cellular targeting and uptake of DSPE-PEG(2000)-amine-containing nanoparticles.4,5 1.Sloat, B.R., Sandoval, M.A., Li, D., et al.In vitro and in vivo anti-tumor activities of a gemcitabine derivative carried by nanoparticlesInt. J. Pharm.409(1-2)278-288(2011) 2.Abd-Rabou, A.A., Bharali, D.J., and Mousa, S.A.Taribavirin and 5-fluorouracil-loaded pegylated-lipid nanoparticle synthesis, p38 docking, and antiproliferative effects on MCF-7 breast cancerPharm. Res.35(4)76(2018) 3.Affram, K., Udofot, O., Singh, M., et al.Smart thermosensitive liposomes for effective solid tumor therapy and in vivo imagingPLoS One12(9):e0815116(2017) 4.Wang, L.-S., Wu, L.-C., Lu, S.-Y., et al.Biofunctionalized phospholipid-capped mesoporous silica nanoshuttles for targeted drug delivery: Improved water suspensibility and decreased nonspecific protein bindingACS Nano4(8)4371-4379(2010) 5.Wen, X., Wang, K., Zhao, Z., et al.Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticlesPLoS One9(9):e106652(2014)

7α-Thiomethylspironolactone is a major metabolite of the synthetic steroid spironolactone.1,2 1.Jankowski, A., Skorek-Jankowska, A., and Lamparczyk, H.Simultaneous determination of spironolactone and its metabolites in human plasmaJ. Pharm. Biomed. Anal.14(8-10)1359-1365(1996) 2.Gardiner, P., Schrode, K., Quinlan, D., et al.Spironolactone metabolism: Steady-state serum levels of the sulfur-containing metabolitesJ. Clin. Pharmacol.29(4)342-347(1989)

C26 Sphingomyelin is a sphingolipid that has been found in serum and cell or brain extracts.1,2,3C26 sphingomyelin levels are increased in the serum of patients with hemophagocytic lymphohistiocytosis, an inflammatory condition characterized by excessive immune activation.3C26 sphingomyelin has been used a component of monolayers to study the influence of sphingomyelin acyl chain length on sphingomyelin-sterol interactions.4[Matreya, LLC.] 1.Wang, J.-R., Zhang, H., Yau, L.D., et al.Improved sphingolipidomic approach based on ultra-high performance liquid chromatography and multiple mass spectrometries with application to cellular neurotoxicityAnal. Chem.86(12)5688-5696(2014) 2.Willmann, J., Mahlstedt, K., Leibfritz, D., et al.Characterization of sphingomyelins in lipid extracts using a HPLC-MS-offline-NMR methodAnal. Chem.79(11)4188-4191(2007) 3.Jenkins, R.W., Clarke, C.J., Lucas, J.T., Jr., et al.Evaluation of the role of secretory sphingomyelinase and bioactive sphingolipids as biomarkers in hemophagocytic lymphohistiocytosisAm. J. Hematol.88(11)E265-E272(2013) 4.Li, X.M., Momsen, M.M., Brockman, H.L., et al.Sterol structure and sphingomyelin acyl chain length modulate lateral packing elasticity and detergent solubility in model membranesBiophys. J.85(6)3788-3801(2003)

Deltorphin II is a peptide agonist of δ2-opioid receptors.1,2It is selective for δ-opioid receptors over μ- and κ-opioid receptors in radioligand bindings assays (Kis = 0.0033, >1, and >1 μM, respectively) and induces [35S]GTPγS binding in mouse brain membrane preparations (EC50= 0.034 μM). Deltorphin II (0.12 mg/kg) decreases the infarction zone:risk zone ratio in a rat model of myocardial ischemia-reperfusion injury induced by coronary occlusion, an effect that can be reversed by the δ2-opioid receptor antagonist naltriben but not the δ1-opioid receptor antagonist BNTX.3Intrathecal administration of deltorphin II (15 μg/animal) increases latency to withdraw in the paw pressure and tail-flick tests in rats.4 1.Raynor, K., Kong, H., Chen, Y., et al.Pharmacological characterization of the cloned κ-, δ-, and μ-opioid receptorsMol. Pharm.45(2)330-334(1994) 2.Scherrer, G., Befort, K., Contet, C., et al.The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: A parallel study of mu, delta and combinatorial opioid receptor knockout miceEur. J. Neurosci.19(8)2239-2248(2004) 3.Maslov, L.N., Barzakh, E.I., Krylatov, A.V., et al.Opioid peptide deltorphin II simulates the cardioprotective effect of ischemic preconditioning: role of δ2-opioid receptors, protein kinase C, and KATP channelsBull. Exp. Biol. Med.149(5)591-593(2010) 4.Labuz, D., Toth, G., Machelska, H., et al.Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin II in rat spinal cord: A search for selectivity of delta receptor subtypesNeuropeptides32(6)511-517(1998)

14S(15R)-EET is an oxylipin and a cytochrome P450 metabolite of arachidonic acid .114S(15R)-EET binds to isolated guinea pig monocytes with a Kivalue of 612.5 nM in a competitive binding assay using [3H]14(15)-EET.2It induces dilation of precontracted isolated canine epicardial arterioles (EC50= 4 pM) and denuded porcine subepicardial arterioles (EC50= 3 pM).3Unlike 14R(15S)-EET, 14S(15R)-EET does not inhibit COX in enzyme assays or isolated platelets.4 1.Daikh, B.E., Lasker, J.M., Raucy, J.L., et al.Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C91J. Pharmacol. Exp. Ther.271(3)1427-1433(1994) 2.Wong, P.Y.-K., Lai, P.-S., and Falck, J.R.Mechanism and signal transduction of 14 (R), 15 (S)-epoxyeicosatrienoic acid (14,15-EET) binding in guinea pig monocytesProstaglandins Other Lipid Mediat.62(4)321-333(2000) 3.Zhang, Y., Oltman, C.L., Lu, T., et al.EET homologs potently dilate coronary microvessels and activate BKCa channelsAm. J. Physiol. Heart Circ. Physiol.280(6)H2430-H2440(2001) 4.Fitzpatrick, F.A., Ennis, M.D., Baze, M.E., et al.Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acidsJ. Biol. Chem.261(2)15334-15338(1986)