k 22

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

UK 227786 is an inhibitor of phosphodiesterase 5 (PDE5), used for treatment of prostatic diseases.

CK 2289 is an inhibitor of type III cyclic 3'5' -adenosine monophosphate phosphodiesterase with potential use in the treatment of congestive heart failure.

FK 224 is an antagonist of tachykinin receptor.

GSK 224876 is a novel next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI). It has activity against efavirenz-resistant strains in the treatment of treatment-naive HIV-1-infected subjects.

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].

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)

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)

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.

Multi-Leu peptide (ML-peptide), with a K i value of 22 nM, acts as a potent inhibitor of PACE4 by competitively binding to its active site and mimicking its substrate sequence, thus suppressing the enzyme's catalytic function. This compound is useful for investigating PACE4's specific role in the progression of prostate cancer.

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].

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].

CDK-IN-9 (compound 24) is a potent inhibitor of CDK and acts on CDK2 E (IC50: 4 nM). It functions as a molecular gel that induces interaction between CDK12 and DDB1, and can dephosphorylate retinoblastoma protein and RNA polymerase II, thereby inducing apoptosis.

Balicatib (AAE581) is a potent and selective inhibitor of cathepsin K, used in trials studying the treatment of osteoporosis.