tandem

TANDEM (quinoxaline) is a synthetic analog of antibiotics quinoxaline.

SETDB1-TTD-IN-1 is a potent and selective inhibitor of SET domain bifurcated protein 1 tandem tudor domain (SETDB1-TTD, Kd = 88 nM), and also an endogenous binder competitive inhibitor with a KD of 0.106±0.002 μM for TTD. It can be used to study the biological functions and disease associations of SETDB1-TTD.

Glutarylcarnitine (O-glutaroyl-L-carnitine) is a diagnostic metabolite for malonic aciduria and glutaric aciduria type I monitored in most tandem mass spectrometry newborn screening programmes.

HM43239 is an orally active and selective FLT3 inhibitor with IC 50 s of 1.1 nM, 1.8 nM and 1.0 nM for FLT3 WT, FLT3 internal tandem duplication (ITD) and FLT3 D835Y kinases, respectively. HM43239 directly inhibits the kinase activity of FLT3 as a reversible Type I inhibitor and effectively modulates downstream p-STAT5 and p-ERK. HM43239 also demonstrated inhibition of SYK, JAK1 2 and TAK1. HM43239 inhibits the proliferation and induces the apoptosis of leukemic cells [1] [2] [3].

Dimetridazole is a nitroimidazole-based compound with antibacterial and anticoccidial activity. It was once widely used in the treatment of parasitic infections in poultry, cattle, swine and farmed fish until suspected to be carcinogenic and mutagenic to humans. Hydroxy dimetridazole is a metabolite of dimetridazole that may be useful for identifying this nitroimidazole in various agricultural samples through liquid chromatography-tandem mass spectrometry and other methods.

Bractoppin is a drug-like inhibitor of phosphopeptide recognition by the human BRCA1 tandem (t)BRCT domain (IC50 = 0.074 μM), which selectively inhibits substrate binding with nanomolar potency in vitro. Structure-activity exploration suggests that Bractoppin engages BRCA1 tBRCT residues recognizing pSer in the consensus motif, pSer-Pro-Thr-Phe, plus an abutting hydrophobic pocket that is distinct in structurally related BRCT domains, conferring selectivity.

Glutarylcarnitine lithium, a key diagnostic metabolite for malonic aciduria and glutaric aciduria type I, is routinely monitored in the majority of newborn screening programs utilizing tandem mass spectrometry [1].

Tolmetin β-D-Glucuronide has reactive properties with human serum albumin, allowing identification of the binding site and reaction mechanism by tandem mass spectrometry.

Desmorpholinyl Quizartinib-PEG2-COOH is a compound featuring an FLT-3 ligand and a PEG-based PROTAC linker. It is employed in the synthesis of PROTAC FLT-3 degrader 1, which serves as a degrader for the FLT-3 internal tandem duplication (ITD) through PROTAC technology. The degrader exhibits an IC50 of 0.6 nM.

O-desmethyl Brinzolamide is an active metabolite of the carbonic anhydrase (CA) inhibitor brinzolamide .1,2It inhibits CAII and CAIV (IC50s = 0.136 and 165 nM, respectively).1 1.Huang, Q., Rui, E.Y., Cobbs, M., et al.Design, synthesis, and evaluation of NO-donor containing carbonic anhydrase inhibitors to lower intraocular pressureJ. Med. Chem.58(6)2821-2833(2015) 2.Lo Faro, A.F., Tini, A., Gottardi, M., et al.Development and validation of a fast ultra-high-performance liquid chromatography tandem mass spectrometry method for determining carbonic anhydrase inhibitors and their metabolites in urine and hairDrug Test Anal.13(8)1552-1560(2021)

Tumor protein p53 binding protein (53BP1) has been identified in a yeast two-hybrid screen as a protein that interacts with the central DNA–binding domain of p532. Similar to breast cancer susceptibility gene 13, 4 (BRCA1; 53BP1 enhances p53-dependent tra

Vixtimotamab (AMV-564; TandAb T564), a bispecific tetravalent tandem diabody (TandAb), selectively targets human CD33 and CD3 antigens, and is used in acute myeloid leukemia (AML) research [1].

3,4-Dehydro Cilostazol (OPC-13015), an active metabolite of Cilostazol, is used for pharmacokinetic studies[1].

PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD) with an IC50 of 0.6 nM and exhibits anti-proliferative activity.

NV03 is a potent and selective antagonist of the UHRF1 (Ubiquitin-like with PHD and RING finger domains 1)-H3K9me3 interaction, binding to the UHRF1 tandem tudor domain with a Kd of 2.4 μM. NV03 holds potential as an anticancer therapeutic [1].

trans-carboxy Glimepiride is a metabolite of the sulfonylurea glimepiride .1It is formed from glimepiride in a two-step process mediated by the cytochrome P450 (CYP) isoform CYP2C9 and cytosolic enzymes. 1.Noh, K., Kim, E., Jeong, T.C., et al.Simultaneous determination of glimepiride and its metabolites in human plasma by liquid chromatography coupled to a tandem mass spectrometryArch. Pharm. Res.34(12)2073-2078(2011)

5,6-dimethyl-2-Thiouracil is a heterocyclic building block that has been used in the synthesis of anti-HIV-1 pyrimidinones.1 It has also been used as an internal standard for the quantification of thyreostats, including 2-thiouracil, in bovine plasma.2 |1. Navrotskii, M.B. Synthesis and anti-HIV-1 activity of new 2-[(2-phthalimidoethyl)thio]-4(3H)-pyrimidinone derivatives. Pharm. Chem. J. 39(9), 466-467 (2005).|2. Schmidt, K.S. In-house validation and factorial effect analysis of a liquid chromatography-tandem mass spectrometry method for the determination of thyreostats in bovine blood plasma. Anal. Bioanal. Chem. 406(3), 735-743 (2014).

ITIC-4F, an indacenodithienothiophene (IDTT)-based postfullerene electron acceptor, exhibits wide applicability in high-efficiency binary and ternary single-junction as well as tandem polymer solar cells (PSCs).

5-hydroxy Flunixin is a metabolite of the COX inhibitor flunixin .1 1.Daeseleire, E., Mortier, L., De Ruyck, H., et al.Determination of flunixin and ketoprofen in milk by liquid chromatography-tandem mass spectrometryAnal. Chim. Acta488(1)25-34(2003)

The DYKDDDDK-tag system utilizes a short, hydrophilic 8- amino-acid peptide that is fused to the protein of interest1. The DYKDDDDK peptide binds to the antibody M1. To improve the detection of the DYKDDDDK tag the 3x (DYKDDDDK) system has been developed.

FLT3 ITD-IN-1 (Compound 1) is a highly potent inhibitor of FLT3 internal tandem duplications (FLT3-ITD) with IC50 values of 38.2 nM for FLT3 and 144.1 nM for FLT3-ITD, and shows exceptional antiproliferative activities against several acute myeloid leukemia cell lines [1].

Cholesteryl behenate is a standard in electrospray ionization tandem mass spectrometry for the analysis of cholesteryl esters and cholesterol.

Y18501, an oxysterol-binding protein (OSBPI) inhibitor structurally akin to Oxathiapiprolin, demonstrates potent inhibition against Phytophthora spp. and Pseudoperonospora cubensis with EC50 values between 0.0005 and 0.0046 μg/mL. It exhibits exceptional protective and curative effects on P. cubensis. When used in tandem with Chlorothalonil, Y18501 markedly enhances the suppression of P. cubensis [1].

53BP1-binding protein 1 (53BP1) engages with dimethylated lysine 20 on histone 4 (H4K20me2) through its tandem tudor domains within a homodimer configuration, crucial for the DNA damage response. UNC2170, a micromolar 53BP1 ligand, selectively interacts with this site, demonstrating at least 17-fold preference for 53BP1 over similar proteins. This interaction occurs in a pocket formed by the 53BP1's tudor domains. Moreover, UNC2170 acts as an antagonist to 53BP1 in cellular lysates, effectively inhibiting class switch recombination, a process dependent on the functional 53BP1 tudor domain, thus confirming its cellular activity.

NPBA, a potassium K2P channel TASK-3 (KCNK9) agonist, concurrently functions as a blocker of the tandem pore domain weak inward rectifying K+ channel (TWIK2). This compound effectively inhibits NLRP3 inflammasome activation in macrophages [1].

C 101248 is a selective and potent inhibitor targeting both mouse and human tandem pore domain halothane-inhibited K+ channel 1 (THIK-1, IC50= 50 nM), without affecting the K2P family members (TREK-1, TWIK-2) and Kv2.1. This compound effectively blocks tonic and ATP-evoked THIK-1 K+ currents as observed in whole-cell patch-clamp recordings of mouse hippocampal microglia. Additionally, C 101248 mitigates neuroinflammation by inhibiting the NLRP3-dependent release of IL-1β in isolated microglia.

Sorafenib N-oxide is an active metabolite of sorafenib , an inhibitor of Raf-1, B-RAF, and receptor tyrosine kinases. Sorafenib N-oxide inhibits FLT3 that contains the internal tandem duplication mutation (FLT3-ITD; Kd = 70 nM) and inhibits proliferation of MV4-11 acute myeloid leukemia (AML) cells expressing FLT3-ITD (IC50 = 25.8 nM). It is selective for AML cell lines containing FLT3-ITD over lines containing wild-type FLT3 (IC50s = 3.9-13.3 μM). Sorafenib N-oxide is also a linear-mixed inhibitor of the cytochrome P450 (CYP) isoform CYP3A4 (Ki = 15 μM in human liver microsomes).

Flavone glycoside from Robinia with antibacterial and diuretic properties; derived from kaempferol.The ability of robinin to reverse the multidrug resistance of the human colon cancer cell line Colo 320 expreβing MDR1 LRP was explored by monitoring their uptake of Rhodamine 123, but was shown to have minimal effect. Robinin (NSC-9222) was detected in lysates of the human breast cancer cell line MCF-7 using liquid chromatography-tandem maβ spectrometry.

FLT3 ITD-IN-4 (Compound 16) is a selective inhibitor of FLT3 internal tandem repeat mutations (FLT3-ITD) with an IC50 of 2.3 nM and is applicable for studying acute myeloid leukemia.

N-desmethyl Rosuvastatin is an active metabolite of the HMG-CoA reductase inhibitor rosuvastatin .1,2N-desmethyl Rosuvastatin is formed when rosuvastatin undergoes demethylation, primarily by the cytochrome P450 (CYP) isoform CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4.1 1.Macwan, J.S., Ionita, I.A., and Akhlaghi, F.A simple assay for the simultaneous determination of rosuvastatin acid, rosuvastatin-5S-lactone, and N-desmethyl rosuvastatin in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS)Anal. Bioanal. Chem.402(3)1217-1227(2012) 2.Bai, X., Wang, X.P., He, G.D., et al.Simultaneous determination of rosuvastatin, rosuvastatin-5 S-lactone, and N-desmethyl rosuvastatin in human plasma by UPLC-MS/MS and its application to clinical studyDrug Res. (Stuttg.)68(6)328-334(2018)

Tuspetinib (HM43239) hydrate is a selectively active FLT3 inhibitor for oral administration, demonstrating IC₅₀ values of 1.1 nM for FLT3 WT, 1.8 nM for FLT3 internal tandem duplication (ITD), and 1.0 nM for FLT3 D835Y kinases. As a reversible type I inhibitor, it suppresses FLT3 kinase activity and influences signaling pathways including p-STAT5, p-ERK, SYK, JAK1 2, and TAK1. Additionally, Tuspetinib hydrate inhibits leukemic cell proliferation and triggers apoptosis [1] [2] [3].