phosphorylase

Glycogen phosphorylase-IN-1 is a selective and potent inhibitor of human hepatic glycogen phosphorylase (hlGPa) with inhibitory effects on hlGPa activity and on hepatocyte glycogen-derived glucose production, and can be used in the study of type 2 diabetes mellitus and canine lupus.

Maltose phosphorylase, a dimerase belonging to family 65 of the glycoside hydrolases [1], catalyzes the conversion of maltose and inorganic phosphate into β-D-glucose-1-phosphate and glucose.

Sucrose phosphorylase, a bacterial transglucosidase, catalyzes the conversion of sucrose and phosphate into α-D-glucose-1-phosphate and D-fructose. This enzyme can also hydrolyze glucosylated sucrose into α-D-glucose or transfer the glucosyl group to a receptor's hydroxyl group, resulting in new α-D-glucoside products. Its enzymatic activity towards the base, substrate, and product is weak [1].

Purine Nucleoside Phosphorylase, an essential enzyme in purine metabolism, plays a critical role in the purine salvage pathway. Its deficiency impairs T cell function. With inorganic orthophosphate as a co-substrate, this enzyme catalyzes the cleavage of the glycosidic bond linking ribose and deoxyribonucleoside, resulting in the production of a purine base and ribose (deoxyribose)-1-phosphate [1].

D-galactosyl-β1-3-N-acetyl-D-hexosamine phosphorylase (BiGalHexNAcP), a member of the CAZy glycoside hydrolase family GH112, plays a pivotal role in biochemical research by catalyzing the phosphorolysis of lacto-n-biose and galacto-n-biose, yielding Gal-1-P and the corresponding N-acetyl-D-hexosamine [1].

Phosphorylase Kinase β-Subunit Fragment (420-436) is a peptide fragment (430-436) derived from the β-Subunit of phosphorylase kinase. Phosphorylase kinase, a serine threonine-specific protein kinase, plays a crucial role in activating glycogen phosphorylase for the release of glucose-1-phosphate from glycogen [1].

Staurosporine (AM-2282) is a protein kinase inhibitor with ATP-competitive and non-selective inhibitory activity (IC50=6 15 2 3 3000 nM) against PKC, PKA, c-Fgr, phosphorylase kinase and TAOK2. Staurosporine also induces apoptosis.

Doxifluridine (AMC 0101) is a fluoropyrimidine derivative and oral prodrug of the antineoplastic agent 5-fluorouracil (5-FU) with antitumor activity. Doxifluridine, designed to circumvent the rapid degradation of 5-FU by dihydropyrimidine dehydrogenase in the gut wall, is converted into 5-FU in the presence of pyrimidine nucleoside phosphorylase. 5-FU interferes with DNA synthesis and subsequent cell division by reducing normal thymidine production and interferes with RNA transcription by competing with uridine triphosphate for incorporation into the RNA strand.

Tipiracil hydrochloride (MA-1 hydrochloride) is a thymidine phosphorylase inhibitor (TPI). Tipiracil hydrochloride is one of the active components in TAS-102, which is an anticancer drug candidate currently in clinical trials.

5-fluorouridine is also known as FUrd, 5-Fluorouracil 1-beta-D-ribofuranoside, 5-Fur, or 5-Fluoro-uridine. 5-fluorouridine is a solid. This compound belongs to the pyrimidine nucleosides and analogues. These are compounds comprising a pyrimidine base attached to a sugar. 5-fluorouridine is known to target uridine phosphorylase. FUrd is often used in chemical and biochemical comparison studies with fluorouracil and thymine analogs.

Disodium monofluorophosphate (NSC248) is a competitive inhibitor of pyruvate kinase and alkaline phosphatase, which also irreversibly inhibits phosphorylase phosphatase.

2'-Deoxyinosine (Guanine deoxyriboside) inhibits the growth of human colon-carcinoma cell lines and is associated with purine nucleoside phosphorylase (PNP) deficiency.

3'-Deoxy-3'-fluoroguanosine is a nucleoside phosphorylase inhibitor that inhibits RNA replication by binding replons. 3 '-Deoxy-3' -fluoroguanosine is used to treat viral hepatitis, cancer and other diseases.

Peldesine (BCX 34) is an effective, competitive, reversible, and orally active inhibitor of purine nucleoside phosphorylase. Peldesine inhibits T-cell proliferation with an IC50 of 800 nM. Peldesine can be used in research on cutaneous T-cell lymphoma, psoriasis and HIV infection.

Ulodesine (BCX4208) is a purine nucleoside phosphorylase (PNP) inhibitor that inhibits PNP with an IC50 value of 2.293 nM/L. Ulodesine may be used to study hyperuricaemia.

Allopurinol riboside is a metabolite of allopurinol with potency against parasites. Allopurinol riboside competitively inhibits the action of purine nucleoside phosphorylase on inosine with a Ki of 277 μM.

AVE5688, an inhibitor of glycogen phosphorylase (GP), has IC50 values of 430 nM and 915 nM, and Kd values of 170 nM and 530 nM for rmGPb and rmGPa, respectively. It is suitable for research on type 2 diabetes.

UDP-sugar pyrophosphorylase (BlUSP) is an enzyme that activates glucose-1-phosphate (Glc-1-P) to UDP-glucose (UDP-Glc) and catalyzes the reversible transfer of the uridyl group from UTP to sugar-1-phosphate, yielding UDP-sugar and pyrophosphate (PPi) [1].

K-252a is a staurosporine analog isolated from Nocardiopsis sp. soil fungi. K-252a inhibits protein kinase (IC50: 470 nM, 140 nM, 270 nM, and 1.7 nM for PKC, PKA, Ca2+/calmodulin-dependent kinase type II, and phosphorylase kinase, respectively).

MT-DADMe-ImmA (MTDIA) is an inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP, Ki: 90 pM).

2'-Fluoro-2'-Deoxyadenosine is efficiently cleaved to the toxic 2-fluoroadenine (FAde) by Escherichia coli purine nucleoside phosphorylase (PNP). 2'-Fluoro-2'-Deoxyadenosine showed good in vivo activity against tumors expressing E. coli PNP. 2'-Fluoro-2'-Deoxyadenosine can be used to synthesize 2'-deoxy-2'-fluoromodified oligonucleotides that can hybridize to RNA.

6-Hydroxypyridin-2(1H)-one hydrochloride (2,6-Dihydroxypyridine hydrochloride) is a reagent used to synthesize uridine phosphorylase inhibitors that increase Uridine (Urd) [U829910] levels, which serves as a promising biochemical modulator to reduce 5-fluorouracil (5-FU) toxicity without impairing its antitumor activity.

SIBA (5'-Deoxy-5'-isobutylthioadenosine) is a synthetic analogue of SAH, acts as an inhibitor of S-adenosylmethionine-mediated transmethylation. SIBA can interfere with a variety of enzymatic activities in vitro, such as SAH hydrolase, methylthioadenosine phosphorylase and cAMP phosphodiesterase. SIBA reversibly blocks the multiplication of herpes simplex type 1 virus (HSV)

1,4-Dideoxy-1,4-imino-D-arabinitol (DAB) functions as an inhibitor of glycogen phosphorylase, a crucial enzyme in glycogenolysis, demonstrating the ability to hinder this process in isolated liver cells (IC50= 1.0 µM) and cerebral cortex and cerebellum homogenates (IC50s = 463 and 383 nM, respectively). Employed extensively in different animal models, DAB inhibits glycogenolysis within the liver and brain.

α-D-Glucose-1-phosphate is an intermediate in glycogen metabolism.1,2It is a precursor in the biosynthesis of UDP-glucose, the glucose donor in glycogen biosynthesis.2α-D-Glucose-1-phosphate can be formed during glycogen breakdownviaphosphorolytic cleavage of glycogen by glycogen phosphorylase.1It can be converted to glucose-6-phosphate by phosphoglucomutase. α-D-Glucose-1-phosphate is combined with CTP by α-D-glucose-1-phosphate cytidylyltransferase to form CDP-glucose in the first step of CDP-D-tyvelose biosynthesis inS. typhi.3Bacterial sucrose phosphorylase converts sucrose and phosphate into D-fructose and α-D-glucose-1-phosphate.4 1.Berg, J.M., Tymoczko, J.L., and Stryer, L.Glycogen breakdown requires the interplay of several enzymesBiochemistry(2002) 2.Berg, J.M., Tymoczko, J.L., and Stryer, L.Glycogen is synthesized and degraded by different pathwaysBiochemistry(2002) 3.Koropatkin, N.M., and Holden, H.M.Molecular structure of ɑ-D-glucose-1-phosphate cytidylyltransferase from Salmonella typhiJ. Biol. Chem.279(42)44023-44029(2004) 4.Goedl, C., Schwarz, A., Minani, A., et al.Recombinant sucrose phosphorylase from Leuconostoc mesenteroides: Characterization, kinetic studies of transglucosylation, and application of immobilised enzyme for production of ɑ-Ｄ-glucose 1-phosphateJ. Biotechnol.129(1)77-86(2007)

CP-320626 is an effective inhibitor of glycogen phosphorylase A (LGPA) in the human liver and GPA in the human muscle. Can act synergistically with glucose. It is a possible target for the treatment of type 2 diabetes.

Maltoheptaose hydrate, a maltooligosaccharide composed of seven glucose units, serves as an activator of phosphorylase B for the preparation of heptulose-2-phosphate.

AVE 9423 is an allosteric glycogen phosphorylase inhibitor.

AGI-24512 is a potent inhibitor of methionine adenylyltransferase 2α (MAT2A) (IC50: 8 nM).AGI-24512 shows antiproliferative activity in MTAP-deficient cancer cells.AGI-24512 inhibits MAT2A, which causes DNA damage in MTAP, and is often used in conjunction with anticancer compounds in cancer research.

glycogen phosphorylase inhibitor

D-Ribofuranose 1-dihydrogen phosphate dicyclohexanamine, commonly referred to as ribose 1-phosphate, serves as a precursor in the synthesis of 5-fluorouracil (FUra) via uridine phosphorylase [1].

Adipokinetic hormone I (Locusta migratoria) (Lom-AKH-I), an insect adipokinetic hormone (AKH), increases fat body cAMP levels in vitro and regulates the mobilization of carbohydrates and lipids from fat body stores for flight, through AKH receptor(s)' association with cAMP production and glycogen phosphorylase activation via the stimulatory guanine nucleotide-binding protein (Gs) [1] [3].

Bayogenin is an alfalfa saponin, Bayogenin shows moderate potency of glycogen phosphorylase inhibition.

Malantide TFA, a synthetic dodecapeptide, originates from the phosphorylation site targeted by cAMP-dependent protein kinase (PKA) on the β-subunit of phosphorylase kinase. Exhibiting a high specificity for PKA with a Michaelis constant (Km) of 15 μM, this compound demonstrates more than 90% inhibition of substrate phosphorylation in the presence of protein inhibitor (PKI) across various rat tissue extracts [1]. Moreover, Malantide TFA acts as an effective substrate for Protein Kinase C (PKC) with a Km of 16 μM [2].

N6-Methyladenosine 5'-monophosphate disodium salt is a glycogen phosphorylase b activator (Ka of 22 μM).

8-Aminoinosine is an endogenous 8-aminopurine that induces diuresis, natriuresis, and glucosuria by inhibiting purine nucleoside phosphorylase (PNPase).

MDL-74428 is an inhibitor of purine nucleoside phosphorylase.

Maltoheptaose (aka amyloheptaose) is a activater of phosphorylase B specifically to prepare (neurosin)heptulose-2-phosphate.

5-Aza-7-deazaguanine is a substrate for E. coli purine nucleoside phosphorylase (wild-type Ser90Ala mutant) in the synthesis of base-modified nucleosides.

Forodesine (BCX-1777) is an orally active and potent purine nucleoside phosphorylase (PNP) inhibitor, a new purine nucleoside analog, inhibitor of human lymphocyte proliferation, induces apoptosis in leukemic cells by increasing dGTP levels, and may be useful in the study of cutaneous T-cell lymphomas.

CP-316819 (GPi 819) is a potent inhibitor of glycogen phosphorylase (GPase) with hypoglycemic effects, inhibits huSMGPa and huLGPa, maintains neuronal activity during hypoglycemia, and can be used in the study of hyperglycemia.

Forodesine hydrochloride (BCX-1777 hydrochloride), a potent inhibitor of human lymphocyte proliferation, effectively induces apoptosis in leukemic cells by elevating dGTP levels. This compound is an orally active, highly potent purine nucleoside phosphorylase (PNP) inhibitor, demonstrating IC50 values between 0.48 to 1.57 nM across human, mouse, rat, monkey, and dog PNP.

The cyanobacterium Nodularia spumigena often contaminates the drinking water of rural communities in developing countries and accumulates in mussels, flounder, and cod from the northern Baltic Sea. Nodularin is a hepatotoxic monocylic pentapeptide produced by the N. spumigena. It is a potent inhibitor of protein phosphatase types 1 (PP1) and 2A (PP2A), exhibiting IC50 values of 1.8 and 0.026 nM, respectively. PP2B is inhibited to a lesser extent with an IC50 of 1.8 μM. No apparent inhibitory effect is observed with PP2C, alkaline phosphatase, acid phosphatase, insulin receptor tyrosine kinase, protein kinase A, phosphorylase kinase, or protein kinase C.

CI 972 anhydrous is an inhibitor of purine nucleoside phosphorylase (PNP) (Ki: 0.83 μM) used as a T cell-selective immunosuppressive agent.

5-Iodotubercidin (NSC-113939) is a potent adenosine kinase inhibitor with IC50 of 26 nM. It inhibits nucleoside transporter, CK1, insulin receptor tyrosine kinase, phosphorylase kinase, PKA, CK2 and PKC.

7-oxo Staurosporine is an antibiotic originally isolated from S. platensis with diverse biological activites. It inhibits PKC, PKA, phosphorylase kinase, EGFR, and c-Src in vitro (IC50s = 9, 26, 5, 200, and 800 nM, respectively). 7-oxo Staurosporine induces cell cycle arrest in the G2/M phase in human leukemia K562 cells with a minimal effective dose (MED) of 30 ng/ml. It is cytotoxic to P388 mouse leukemia cells that are resistant and susceptible to doxorubicin . 7-oxo Staurosporine inhibits growth of the mycelial, but not yeast form of C. albicans, C. krusei, C. tropicalis, and C. lusitaniae (MICs = 3.1-25 μg/ml). It increases sphingomyelin synthesis in CHO-K1 cells when used at a concentration of 50 nM.

Erythrofuranosyladenine(9-beta-D-Erythrofuranosyladenine, ETA) is a nontoxic MTAP substrate. Erythrofuranosyladenine is an effective salvage agent for methylthioadenosine phosphorylase–selective therapy of T-cell acute lymphoblastic leukemia with L-alanos

9-Deazaguanine, a nucleoside analog, demonstrates strong inhibitory activity against purine nucleoside phosphorylase (PNP) [1].

Peldesine (BCX 34) dihydrochloride is a potent, competitive, reversible, and orally active inhibitor of purine nucleoside phosphorylase (PNP), with IC50 values of 36 nM, 5 nM, and 32 nM against human, rat, and mouse red blood cell (RBC) PNP, respectively. Additionally, it inhibits T-cell proliferation with an IC50 of 800 nM, showing promise for research into cutaneous T-cell lymphoma, psoriasis, and HIV infection [1] [2] [3] [4].

Tipiracil is an inhibitor of thymidine phosphorylase(TPase).