Isotope-Labeled Polyketides

Tylosin-d₃ is the deuterium labeled Tylosin. Tylosin (Tylosin A) is a macrolide antibiotic found naturally as a fermentation product of Streptomyces fradiae. Tylosin exerts potent antimicrobial activity against Gram-positive bacteria. Tylosin is widely used as a feed additive for promoting animal growth. Tylosin is used for veterinary purposes against bacterial dysentery and respiratory diseases in poultry, pigs and cattle.

Tacrolimus-d₃ (FK506-d₃) is the deuterated-labeled Tacrolimus (HY-13756). Tacrolimus (FK506), a molecular glue, a macrocyclic lactone, binds to FK506 binding protein (FKBP) to form a complex. Tacrolimus inhibits calcineurin phosphatase, which inhibits T-lymphocyte signal transduction and IL-2 transcription. Immunosuppressive properties.

Quercetin-¹³C₃ is the ¹³C-labeled Quercetin. Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC₅₀ of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively.

Cyclosporin A-d₁₂ (Cyclosporine A-d₁₂) is the deuterated-labeled Cyclosporin A (HY-B0579). Cyclosporin A (Cyclosporine A) is an immunosuppressant which binds to the cyclophilin and inhibits phosphatase activity of protein phosphatase 2B (PP2B/calcineurin) with an IC₅₀ of 5 nM. Cyclosporin A is a molecular glue, binds to cyclophilin and calcineurin, leading to inactivation of nuclear Factor of activated T Cells (NFAT) and a subsequent decrease in the immune response. Cyclosporin A also inhibits CD11a/CD18 adhesion.

Doxycycline-¹³C,d₃ is ¹³C and deuterium labeled Doxycycline (HY-N0565). Doxycycline is an orally active highly lipophilic, tissue-permeable MMP inhibitor with broad-spectrum antibacterial activity. Doxycycline is also a semi-synthetic antibiotic with chelating properties, which blocks bacterial protein synthesis and inhibits extracellular matrix degradation through interactions with zinc and calcium atoms. Doxycycline also inhibits mitochondrial biogenesis, translation, and the expression of respiratory chain proteins. Doxycycline induces apoptosis, inhibits autophagy and EMT, downregulates stem cell markers, and activates the PI3K-AKT pathway, thereby effectively inhibiting the viability and proliferation of cancer cells such as breast cancer cells. Doxycycline also promotes the survival and self-renewal of embryonic stem cells and neural stem cells, and reduces the frequency of medium changes in culture. Doxycycline has been applied in studies related to breast cancer, prostate cancer, bladder cancer, and other cancers.

Minocycline-d₇ is deuterium labeled Minocycline. Minocycline is an orally active, potent and BBB-penetrated semi-synthetic tetracycline antibiotic. Minocycline is a hypoxia-inducible factor (HIF)-1α inhibitor. Minocycline shows anti-cancer, anti-inflammatory, and glutamate antagonist effects. Minocycline reduces glutamate neurotransmission and shows neuroprotective properties and antidepressant effects. Minocycline inhibits bacterial protein synthesis through binding with the 30S subunit of the bacterial ribosome, resulting in a bacteriostatic effect.

Myricetin-¹³C₃ is the ¹³C-labeled Myricetin. Myricetin is a common plant-derived flavonoid with a wide range of activities including strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities.

Diosmetin-d₃ is the deuterium labeled Diosmetin. Diosmetin is a natural flavonoid which inhibits human CYP1A enzyme activity with an IC50 of 40 μM in HepG2 cell.

3-Methylflavone-8-carboxylic acid-d₅ is the deuterium labeled 3-Methyl-4-oxo-2-phenyl-4H-chromene-8-carboxylic acid.

Emodin-d₄ is the deuterium labeled Emodin. Emodin (Frangula emodin), an anthraquinone derivative, is an anti-SARS-CoV compound. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 (ACE2) interaction. Emodin inhibits casein kinase-2 (CK2). Anti-inflammatory and anticancer effects. Emodin is a potent selective 11β-HSD1 inhibitor with the IC₅₀ of 186 and 86 nM for human and mouse 11β-HSD1, respectively. Emodin ameliorates metabolic disorder in diet-induced obese mice.

Liquiritigenin-d₄ (4',7-Dihydroxyflavanone-d₄) is the deuterium labeled Liquiritigenin (HY-N0377). Liquiritigenin, a flavanone isolated from Glycyrrhiza uralensis, is a highly selective estrogen receptor β (ERβ) agonist with an EC₅₀ of 36.5 nM for activation of the ERE tk-Luc.

α-Zearalenol-d4 is a deuterated labeled α-Zearalenol. α-Zearalenol is a Mycotoxin with high affinity for the estrogen receptors (ER), α-Zearalenol is the derivative of zearalenone (ZEN), causes reproductive disorders in animals, due to its xenoestrogenic effects.

α-Zearalenol-¹³C₁₈ is the ¹³C-labeled α-Zearalenol. α-Zearalenol is a Mycotoxin with high affinity for the estrogen receptors (ER). α-Zearalenol is the derivative of zearalenone (ZEN), causes reproductive disorders in animals, due to its xenoestrogenic effects.

Rotenone-d₃ is the deuterium labeled Rotenone (HY-B1756). Rotenone is a mitochondrial electron transport chain complex I inhibitor. Rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production.

Apigenin-¹³C is the ¹³C-abeled Apigenin (HY-N1201). Apigenin is a competitive CYP2C9 inhibitor with a K_i of 2 μM.

Olivetol-d₉ is the deuterium labeled Olivetol. Olivetol is a naturally phenol found in lichens and produced by certain insects, acting as a competitive inhibitor of the cannabinoid receptors CB1 and CB2[3]. Olivetol also inhibits CYP2C19 and CYP2D6 activities.

Rapamycin-¹³C,d₃-1 (Sirolimus-¹³C,d₃-1) is the deuterated, ¹³C-labeled Rapamycin (HY-10219). Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC₅₀ of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.

Oxytetracycline-d₆ is deuterium labeled Oxytetracycline. Oxytetracycline is an antibiotic belonging to the tetracycline class. Oxytetracycline potent inhibits Gram-negative and Gram-positive bacteria. Oxytetracycline is a protein synthesis inhibitor and prevents the binding from aminoacil-tRNA to the complex m-ribosomal RNA. Oxytetracycline also possesses anti-HSV-1 activity.

Oxytetracycline-d₃ is the deuterium labeled Oxytetracycline (HY-B0275). Oxytetracycline is an antibiotic belonging to the tetracycline class. Oxytetracycline potent inhibits Gram-negative and Gram-positive bacteria. Oxytetracycline is a protein synthesis inhibitor and prevents the binding from aminoacil-tRNA to the complex m-ribosomal RNA. Oxytetracycline also possesses anti-HSV-1 activity.

Spiramycin I-d₃-1 is deuterium-labeled Spiramycin I.