Isotope-Labeled Inhibitors

Deucravacitinib (BMS-986165) is an orally active allosteric inhibitor of tyrosine kinase 2 (TYK2), with an IC₅₀ of 0.2 nM and a K_i of 0.02 nM against the JH2 domain of TYK2, and it exhibits selectivity over other JAK subtypes and most of the kinome. Deucravacitinib blocks IL-23, IL-12, p-STAT1/3 and Type I IFN signaling, and inhibits Th17/Th1-mediated psoriasis inflammation. Deucravacitinib can be used in research related to moderate-to-severe plaque psoriasis, inflammatory bowel disease and systemic lupus erythematosus.

L-Glutamine-¹³C₅ is the ¹³C-labeled L-Glutamine (HY-N0390). L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na⁺-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.

L-Glutamine-¹⁵N is the ¹⁵N-labeled L-Glutamine (HY-N0390). L-Glutamine is an orally active nutritional agent and cellular metabolism regulator. L-Glutamine is taken up in a Na⁺-dependent manner and targets multiple key molecules including glutaminase, mTORC1, NF-κB, STAT-3 and HIF-1α. L-Glutamine enhances glutaminolytic catabolism, drives the conversion of glutamate to α-ketoglutarate, thereby regulating gene expression, integrating metabolic signals, mediating glutamine flux and maintaining redox homeostasis. L-Glutamine also promotes cell proliferation, osteogenic differentiation and fracture healing, exerts neuroprotective and cardioprotective effects, and inhibits osteoarthritis. L-Glutamine can be applied to research related to osteoporosis, osteoarthritis, ischemic stroke and acute cantharidin-induced cardiotoxicity.

Exatecan-d₅ (DX8951f-d₅) mesylate is deuterium labeled Exatecan mesylate (HY-13631A). Exatecan mesylate is a DNA topoisomerase I inhibitor, with an IC₅₀ of 2.2 μM (0.975 μg/mL). Exatecan mesylate can be used in cancer research.

MMAE-d₈ is a deuterated labeled MMAE, a potent mitotic inhibitor and a tubulin inhibitor.

DXd-d₅ is a deuterium labeled DXd. DXd is a potent DNA topoisomerase I inhibitor, with an IC₅₀ of 0.31 μM, used as a conjugated drug of HER2-targeting ADC (DS-8201a) .

Choline-¹³C₂ chloride is the ¹³C-labeled Choline chloride (HY-B1337). Choline chloride is an orally active methylxanthine derivative. Choline chloride exhibits weak antihistaminic and anticholinergic activities and potentiates the effects of histamine and acetylcholine. Choline chloride relaxes bronchial smooth muscle, dilates coronary and peripheral blood vessels, increases urine output and electrolyte excretion, stimulates locomotor activity in the central nervous system, and induces transient hypotension following a pressor phase. Choline chloride modulates sleep architecture by increasing wakefulness time and reducing slow-wave sleep, without altering the frequency or severity of nocturnal hypoxemia, apnea, or hypopnea events. Choline chloride is used in studies of bronchospasm, nocturnal asthma, and chronic asthma.

Deuruxolitinib (CTP-543; Ruxolitinib-d₈) is a deuterated analog of Ruxolitinib (HY-50856) and an orally active, selective inhibitor of JAK1 and JAK2. Deuruxolitinib blocks Janus kinase-mediated cytokine receptor signaling and proinflammatory cytokine gene expression. Deuruxolitinib is primarily metabolized in the liver via CYP2C9. Deuruxolitinib promotes scalp hair regrowth in severe chronic alopecia areata. Deuruxolitinib is used in alopecia areata-related research.

Rosuvastatin-d₃ sodium is the deuterated-labeled Rosuvastatin Sodium (HY-17504B). Rosuvastatin Sodium is a competitive HMG-CoA reductase (HMGCR) inhibitor, with an IC₅₀ of 11 nM. Rosuvastatin Sodium potently blocks hERG current with an IC₅₀ of 195 nM. Rosuvastatin Sodium reduces the expression of the mature hERG and the interaction of heat shock protein 70 (Hsp70) with the hERG protein. Rosuvastatin Sodium effectively lowers low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein levels.

Water-¹⁸O is the ¹⁸O-labeled Water.

Sorafenib-d₃ (Donafenib) is the deuterated-labeled Sorafenib (HY-10201). Sorafenib (Bay 43-9006) is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib inhibits tumor growth and metastasis in mouse and rat models. Sorafenib can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

Adenosine-¹³C₅ is the ¹³C labeled Adenosine. Adenosine (Adenine riboside), a ubiquitous endogenous autacoid, acts through the enrollment of four G protein-coupled receptors: A1, A2A, A2B, and A3. Adenosine affects almost all aspects of cellular physiology, including neuronal activity, vascular function, platelet aggregation, and blood cell regulation.

S-Adenosyl-L-methionine-d₃ (S-Adenosyl methionine-d₃) is the deuterated product of S-Adenosyl-L-methionine (HY-B0617). S-Adenosyl-L-methionine (S-Adenosyl methionine) is an orally active methyl group donor. S-Adenosyl-L-methionine is a dietary supplement with potent antidepressant effects. S-Adenosyl-L-methionine also has anti‑proliferative, pro‑apoptotic and anti‑metastatic roles in cancers. S-Adenosyl-L-methionine has the potential for, cancer, liver disease and osteoarthritis research.

2-Ketoglutaric acid-¹³C₅ (Alpha-Ketoglutaric acid-¹³C₅) is a ¹³C labeled 2-Ketoglutaric acid (HY-W013636). 2-Ketoglutaric acid (Alpha-Ketoglutaric acid) is an intermediate in the production of ATP or GTP in the Krebs cycle. 2-Ketoglutaric acid also acts as the major carbon skeleton for nitrogen-assimilatory reactions. 2-Ketoglutaric acid is a reversible inhibitor of tyrosinase (IC₅₀=15 mM).

Ammonium chloride-¹⁵N is the ¹⁵N labeled Ammonium chloride (HY-Y1269). Ammonium chloride, as a heteropolar compound with pH value regulation, can cause intracellular alkalization and metabolic acidosis thus effecting enzymatic activity and influencing the process of biological system. Ammonium chloride is an autophagy inhibitor. Ammonium chloride is also a lysosome inhibitor.

Quinolinic acid-d₃ is the deuterium labeled Quinolinic acid. Quinolinic acid, an endogenous metabolite of tryptophan, is a N-methyl-D-aspartate receptor (NMDA receptor) agonist. Quinolinic acid increases glutamate efflux, induces the generation of ROS, activates nitric oxide synthase, produces excessive NO, leading to calcium ion influx and neuronal apoptosis.

Citric acid-¹³C₆ is the ¹³C-labeled Citric acid (HY-N1428). Citric acid is a natural preservative and food tartness enhancer. Citric acid induces apoptosis and cell cycle arrest at G2/M phase and S phase in HaCaT cells. Citric acid cause oxidative damage of the liver by means of the decrease of antioxidative enzyme activities. Citric acid is also an acidulant, emulsifier, sequestrant and buffering agent widely used across many industries.

4'-Hydroxy diclofenac-d₄ is the deuterium labeled 4'-Hydroxy diclofenac. 4'-Hydroxy diclofenac is an orally active metabolite of Diclofenac (HY-15036) by cytochrome P450 2C9 (CYP2C9). 4'-Hydroxy diclofenac has anti-inflammatory and analgesic properties.

Inosine-¹³C₅ is the ¹³C₅ labeled Inosine (HY-N0092). Inosine is an endogenous purine nucleoside produced by catabolism of adenosine. Inosine has anti-inflammatory, antinociceptive, immunomodulatory and neuroprotective effects. Inosine is an agonist for adenosine A₁ (A₁R) and A_2A (A_2AR) receptors.

Kynurenic acid-d₅ is the deuterium labeled Kynurenic acid. Kynurenic acid, an endogenous tryptophan metabolite, is a broad-spectrum antagonist targeting NMDA, glutamate, α7 nicotinic acetylcholine receptor. Kynurenic acid is also an agonist of GPR35/CXCR8.