k 22

LL-K8-22 is a potent, selective, and durable dual degrader of CDK8-cyclin C, demonstrating DC50 values of 2.52 and 2.64 μM, respectively. This compound effectively suppresses STAT1 Ser 727 phosphorylation and inhibits carcinogenic transcriptional programs driven by E2F and MYC. LL-K8-22 is specifically utilized in research for triple-negative breast cancer (TNBC) [1].

ZIKV-IN-K22 is a potent antiviral agent against a broad range of coronaviruses by targeting membrane-bound viral RNA replication, effectively inhibiting ZIKV with IC50 of 2.1 μM.

6-Chloro-2-fluoropurine is a heterocyclic building block.1,2It has been used in the synthesis of purine nucleosides that inhibit cyclin-dependent kinases (CDKs)in vitro.16-Chloro-2-fluoropurine has also been used in the synthesis of purine nucleosides that are active against HIV-1 and hepatitis B virus (HBV)in vitro.2 1.Wilson, S.C., Atrash, B., Barlow, C., et al.Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitorsBioorg. Med. Chem.19(22)6949-6965(2011) 2.Lee, K., Choi, Y., Gullen, E., et al.Synthesis and anti-HIV and anti-HBV activities of 2'-fluoro-2',3'-unsaturated L-nucleosidesJ. Med. Chem.42(7)1320-1328(1999)

IT-143B is a bacterial metabolite that has been found in S. iakyrus.1 It inhibits the proliferation of OS-RC-2 and ACHN cancer cells (IC50s = 22 and 98 μM, respectively). |1. Li, K., Liang, Z., Chen, W., et al. Iakyricidins A-D, antiproliferative piericidin analogues bearing a carbonyl group or cyclic skeleton from Streptomyces iakyrus SCSIO NS104. J. Org. Chem. 84(19), 12626-12631 (2019).

XIIa-IN-1-IN-3 (Compound 22) is a Factor XIIa inhibitor with a K i app of 97.8 nM, used in thrombosis research [1].

Elsilimomab (B-E8), an IgG1 monoclonal antibody targeting interleukin-6 (IL-6), exhibits a dissociation constant (K D) of 22 pM and an inhibitory concentration (IC 50) of 1.4 nM. It is applicable in researching multiple myeloma, renal cell carcinoma, and rheumatoid arthritis (RA) [1] [2] [3].

Heronapyrrole B is a farnesylated 2-nitropyrrole bacterial metabolite that has been found inStreptomycesand has antibacterial activity.1,2It is active against the Gram-positive bacteriaS. aureusandB. subtilis(MICs = 1.8 and 7.5 μM, respectively) but not Gram-negativeP. aeruginosaorE. coli.1 1.Raju, R., Piggott, A.M., Diaz, L.X.B., et al.Heronapyrroles A-C: farnesylated 2-nitropyrroles from an Australian marine-derived Streptomyces spOrg. Lett.12(22)5158-5161(2010) 2.Matsuo, T., Hashimoto, S., Nishikawa, K., et al.Total synthesis and complete stereochemical assignment of heronapyrroles A and BTetrahedron Letters565345-5348(2015)

(E)-10-Hydroxynortriptyline (E-10-OH-NT) is a metabolite of Nortriptyline, a tricyclic antidepressant and the main active metabolite of Amitriptyline, used to relieve the symptoms of depression[1].

AZT triphosphate TFA (3'-Azido-3'-deoxythymidine-5'-triphosphate TFA) is a active triphosphate metabolite of Zidovudine (AZT). AZT triphosphate TFA exhibits antiretroviral activity and inhibits replication of HIV. AZT triphosphate TFA also inhibits the DNA polymerase of HBV. AZT triphosphate TFA activates the mitochondria-mediated apoptosis pathway[1][2][3]. Treatment with 100 μM Zidovudine (AZT) for 48h disrupts the mitochondrial tubular network via accumulation of AZT triphosphate (AZT-TP) in H9c2 cells. AZT triphosphate accumulation causes downregulation of Opa1 and upregulation of Drp1. AZT triphosphate causes mitochondrial dysfunction, increases the production of cytotoxic reactive oxygen species (ROS), and impairs the balance of the mitochondrial quality control system in H9c2 cell model established from rat embryonic myoblasts[1]. [1]. Ryosuke Nomura, et al. Azidothymidine-triphosphate Impairs Mitochondrial Dynamics by Disrupting the Quality Control System. Redox Biol. 2017 Oct;13:407-417. [2]. Takeya Sato, et al. Engineered Human tmpk/AZT as a Novel Enzyme/Prodrug Axis for Suicide Gene Therapy. Mol Ther. 2007 May;15(5):962-70. [3]. K Y Hostetler, et al. Enhanced Oral Absorption and Antiviral Activity of 1-O-octadecyl-sn-glycero-3-phospho-acyclovir and Related Compounds in Hepatitis B Virus Infection, in Vitro. Biochem Pharmacol. 1997 Jun 15;53(12):1815-22.

LSD1-IN-22 is a potent inhibitor of Lysine-specific demethylase 1 (LSD1) with a K_i value of 98 nM, exhibiting anti-proliferative activity against certain cancer cells [1].

RORγ antagonist 1 (compound 22), a potent derivative of betulinic acid, acts as an antagonist to RORγ with a dissociation constant (K D) of 0.18 μM. It demonstrates anti-proliferative effects in the HPAF-II pancreatic cancer xenograft model, inhibits the RAS MAPK and AKT mTORC1 signaling pathways, and triggers caspase-dependent apoptosis in pancreatic cancer cells [1].

BN80933 is a dual inhibitor of lipid peroxidation and neuronal nitric oxide synthase; Neuroprotectant.

Oosporein is a mycotoxin that has been found inBeauveriaand has diverse biological activities.1,2It is cytotoxic to Sf9 and Sf21 insect cells with 50% cytotoxic concentration (CC50) values of 4.23 and 10.43 μM, respectively.3Oosporin induces lethality in day-old cockerels (LD50= 6.12 mg kg).4It inhibits Na+ K+-, Ca2+-, and Mg2+-ATPase activities by 27, 52, and 100%, respectively, in equine erythrocyte ghosts when used at a concentration of 200 μg ml.2Oosporein inhibits herpes simplex 1 (HSV-1), but not HeLa cell orE. coli, DNA polymerase (IC50s = 75, 610, and >700 μM, respectively).5It is active against the bacteriumS. pneumoniae(MIC = 32 μg ml) and the plant pathogenic fungusP. infestans(MIC = 16 μM).1,6 1.Wainwright, M., Betts, R.P., and Teale, D.M.Antibiotic activity of oosporein from Verticillium psalliotaeTrans. Br. Mycol. Soc.86(1)168-170(1986) 2.Jeffs, L.B., and Khachatourians, G.G.Toxic properties of Beauveria pigments on erythrocyte membranesToxicon. 35(8)1351-1356(1997) 3.Arboleda Valencia, J.W., Gaitán Bustamante, A.L., Jiménez, A.V., et al.Cytotoxic activity of fungal metabolites from the pathogenic fungus Beauveria bassiana: An intraspecific evaluation of beauvericin productionCurr. Microbiol.63(3)306-312(2011) 4.Cole, R.J., Kirksey, J.W., Cutler, H.G., et al.Toxic effects of oosporein from Chaetomium trilateraleJ. Agric. Food Chem.22(3)517-520(1974) 5.Terry, B.J., Liu, W.C., Cianci, C.W., et al.Inhibition of herpes simplex virus type 1 DNA polymerase by the natural product oosporeinJ. Antibiot. (Tokyo)45(2)286-288(1992) 6.Nagaoka, T., Nakata, K., Kouno, K., et al.Antifungal activity of oosporein from an antagonistic fungus against Phytophthora infestansZ. Naturforsch. C. J. Biosci.59(3-4)302-304(2004)