Deuterated Drug

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.

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.

Ivacaftor-d₉ is a potent CFTR modulator and exhibits an EC₅₀ value of 255 nM for CFTR potentiation in G551D/F508del HBE Cells. Ivacaftor-D9 acts as an orally active and improved deuterated Ivacaftor analog for cystic fibrosis research.

VX-984 is an orally active, potent, selective and BBB-penetrated DNA-PK inhibitor. VX-984 efficiently inhibits NHEJ (non-homologous end joining) and increases DSBs (DNA double-strand breaks). VX-984 can be used for glioblastomas (GBM) and non-small cell lung cancer (NSCLC) research. VX-984 is a de novo deuterium.

BMS-986202 is a potent, selective and orally active Tyk2 inhibitor that binds to Tyk2 JH2 with an IC₅₀ value of 0.19 nM and a K_i of 0.02 nM. BMS-986202 is remarkably selective over other kinases including Jak family members. BMS-986202 is also a weak inhibitor of CYP2C19 with an IC₅₀ value of 14 μM. BMS-986202 can be used for IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus research. BMS-986202 is a de novo deuterium.

PPARγ agonist-23 (Compound 9) is an orally active PPARγ agonist with an EC₅₀ of 0.32 μM. PPARγ agonist-23 improves hepatic triglyceride levels, reduces scores of steatosis and hepatocellular ballooning, and decreases the total activity score of non-alcoholic steatohepatitis (NASH). PPARγ agonist-23 can be used for the research of non-alcoholic steatohepatitis.

L-838417-d₉ is the deuterium labeled L-838417 (HY-W009009). L-838417 is a selective partial agonist at the α2, α3 and α5 subtypes of the GABA_A receptor and an antagonist at the α1, with binding K_i values of 0.79 nM, 0.67 nM, 1.67 nM, 267 nM, 2.25 nM and 2183 nM for α1β3γ2, α2β3γ2, α3β3γ2, α4β3γ2, α5β3γ2 and α6β3γ2. L-838417 has anti-anxiety activity.

Deuruxolitinib, a deuterated Ruxolitinib (HY-50856), is an orally active JAK1 and JAK2 inhibitor. Deuruxolitinib demonstrates significant hair regrowth effects. Deuruxolitinib can be used for the research of alopecia areata.

Mindeudesivir (JT001; VV116; GS-621763-d₁) hydrobromide is a deuterated version of Remdesivir (HY-104077), a highly orally active nucleoside antiviral against SARS-CoV-2 and respiratory syncytial virus (RSV). Mindeudesivir hydrobromide retains the antiviral activity of Remdesivir against COVID-19, and is the first domestically produced deuterium targeting the COVID-19.

Lomedeucitinib (BMS-986322) is a tyrosine protein kinase (TYK2) inhibitor.

Cys-MC-GGFG-Dxd is a cysteine-modified, cleavable ADC drug-linker conjugate. Cys-MC-GGFG-Dxd consists of a maleimidocaproyl-glycine-glycine-L-phenylalanine-glycine (MC-GGFG) linker and an Exatecan (HY-13631) derivative (DXd) (HY-13631D) payload. Cys-MC-GGFG-Dxd can be further conjugated to anti-HER2 IgG1κ antibody for the synthesis of antibody-drug conjugates (ADC), such as the breast cancer-targeting ADC compound Fam-trastuzumab deruxtecan-nxki (Enhertu).

Tetrabenazine-d₆ (Deutetrabenazine) is a deuterium-labled Tetrabenazine (HY-B0590). Tetrabenazine (Ro 1-9569) is a brain-penetrant and orally active VMAT2-selective ligand with human VMAT2 K_i 100 nM. Tetrabenazine binds VMAT2 to block monoamine uptake into synaptic vesicles, potentiates cytoplasmic monoamine degradation. Tetrabenazine weakly blocks dopamine D2 receptors, and increases dopamine turnover via elevated cerebrospinal fluid homovanillic acid. Tetrabenazine can be used for the research of Huntington’s disease, tardive dyskinesia, and Tourette’s syndrome.

JAK2-IN-11 (Example 6) is a JAK2 kinase inhibitor with IC₅₀ ≤10 nM against JH2 BIND WT/V617F. JAK2-IN-11 has antitumor activity.

Deutenzalutamide (Enzalutamide-d₃) is a developed deuterium labeled Enzalutamide (MDV3100). Enzalutamide is an androgen receptor (AR) antagonist with an IC50 of 36 nM in LNCaP prostate cells.

Tebideutorexant is an OX1R-selective inhibitor with oral bioavailability and blood-brain barrier permeability, with human OX1R pK_i 8.17 and rat OX1R pK_i 8.13.Tebideutorexant selectively modulates OX1R, with no significant functional effect on OX2R. Tebideutorexant can be used for the research of panic and anxiety disorders.

JAK2-IN-10 is a selective JAK2 V617F inhibitor with an IC₅₀ value of ≤10 nM. JAK2-IN-10 can be used for the research of myeloproliferative neoplasms and other related diseases.

Linoleic Acid-d₂ is the deuterium labeled Linoleic acid. Linoleic acid is a common polyunsaturated (PUFA) found in plant-based oils, nuts and seeds. Linoleic acid is a part of membrane phospholipids, and functions as a structural component to maintain a certain level of membrane fluidity of the transdermal water barrier of the epidermis. Linoleic acid induces red blood cells and hemoglobin damage via oxidative mechanism.

(rac)-Lomedeucitinib ((rac)-BMS-986322) is the racemate of Lomedeucitinib. Lomedeucitinib (BMS-986322) is a tyrosine protein kinase (TYK2) inhibitor. Lomedeucitinib has anti-inflammatory activity and significant inhibitory effect on IFNα (IC50=0.047 μM) production downstream of IL-12/TYK2. Lomedeucitinib is indicated for the study of plaque psoriasis and pruritus.

1D228 is a c-Met/TRK inhibitor with antitumor activity. 1D228 inhibits cyclin D1 to induce G0/G1 arrest and inhibit cancer cell proliferation and migration. 1D228 can be used in the study of gastric, liver and vascular tumors.