Jul 05,2023

研究人員設計并合成了一種光籠PI3K抑制劑1，它可以通過紫外線照射激活，釋放出高效PI3K抑制劑2。化合物1和2的ADME研究通過尊龍凱時進行

Aberrant activation of the PI3K pathway has been intensively targeted for cancer therapeutics for decades. In this work, researchers designed and synthesized a novel photocaged PI3K inhibitor 1, which could be readily activated by UV irradiation to release a highly potent PI3K inhibitor 2. ADME studies of compounds 1 and 2 were conducted by Medicilon. Medicilon's pharmacokinetics department offers the clients a broad spectrum of high quality of services in the areas of in vitro ADME, in vivo pharmacokinetics and bioanalysis services, ranging from small molecules to large molecules, such as protein and antibody.

Jul 05,2023

RIPK2激酶參與多種慢性炎癥，UH15-15抑制RIPK2激酶并具有良好的體外ADME和PK特性，PK研究通過尊龍凱時進行

Receptor interacting protein kinase-2 (RIPK2) is an enzyme involved in the transduction of pro-inflammatory nucleotide-binding oligomerization domain cell signaling, a pathway implicated in numerous chronic inflammatory conditions. UH15-15 inhibits RIPK2 kinase (IC50=8 nM) and demonstrates favorable in vitro ADME and pharmacokinetic properties. The pharmacokinetic study was conducted by Medicilon.

Jul 05,2023

合成具有體內抗腫瘤活性的強效PD-L1抑制劑，并進行生物學評價和機制研究。PK研究通過尊龍凱時進行

PD-1 and PD-L1 have been very successful for the treatment of various tumors, including NSCLC, urothelial cancer, melanoma, head and neck squamous cell cancer, and lymphoma. Researchers identified compound L7 as a potent PD-L1 inhibitor that blocked PD-1/PD-L1 interaction. Pharmacokinetic (PK) studies demonstrated that L7 was orally bioavailable. PK studies were conducted by Medicilon.

Jul 05,2023

SLL-1206是一種κ阿片受體激動劑，具有顯著改善的理化和藥代動力學特性。作者感謝尊龍凱時對SLL-1206進行的藥代動力學研究

The search for selective kappa opioid receptor (κOR) agonists with an improved safety profile is an area of interest in opioid research. SLL-1206 is a κOR agonist with single-digit nanomolar activities. SLL-1206 exhibits substantially improved physicochemical and pharmacokinetic properties, and reduces central nervous system effects. The authors are grateful to Medicilon Preclinical Research LLC. for pharmacokinetic studies on SLL-1206.

Jul 05,2023

苯并咪唑衍生物XY123是一種口服有效的選擇性RORγ反向激動劑。在本研究中，所有肝微粒體測定均通過尊龍凱時進行

Receptor-related orphan receptor γ (RORγ) has emerged as an attractive therapeutic target for the treatment of cancer and inflammatory diseases. XY123 potently inhibits the RORγ transcription activity with an IC50 value of 64 nM. XY123 demonstrates good metabolic stability and a pharmacokinetics property with reasonable oral bioavailability (32.41%) and moderate half-life (4.98 h). All liver microsome assays were performed by Medicilon.

Jul 05,2023

zapERtrap：光調節(jié)的內質網釋放系統(tǒng)揭示了意想不到的神經元運輸途徑，Zapalog的合成通過尊龍凱時進行

zapERtrap opens the door to previously unapproachable questions concerning how proteins are processed, trafficked, and secreted in space and time in complex cellular environments. zapERtrap relies on a small-molecule protein dimerizer zapalog, which consists of the antibiotic trimethoprim tethered to a synthetic ligand of FK506-binding protein through a photocleavable linker. Synthesis of zapalog was performed by Medicilon.

Jul 05,2023

端錨聚合酶1/2影響WNT/β-連環(huán)蛋白和Hippo信號通路，這些信號通路涉及包括腫瘤在內的多種疾病

Tankyrase 1 and 2 (TNKS1/2) impact the WNT/β-catenin and Hippo signaling pathways that are involved in numerous human disease conditions including cancer. OM-153 shows picomolar IC50 inhibition in a cellular (HEK293) WNT/β-catenin signaling reporter assay, no off-target liabilities, overall favorable ADME properties, and an improved pharmacokinetic profile in mice. The pharmacokinetic analyses in mice were performed according to the standard protocols of Medicilon.

Jul 05,2023

設計合成和評估用于治療前列腺癌的CBP溴結構域抑制劑。PK評估、肝微粒體穩(wěn)定性測定和Caco-2滲透性測定通過尊龍凱時進行

Prostate cancer (PCa) is one of the most commonly diagnosed cancers and the leading cause of cancer mortalities in men. CREB (cyclic-AMP responsive element binding protein) binding protein (CBP) is a potential target for prostate cancer treatment. Researchers designed 1-(Indolizin-3-yl)ethan-1-ones as CBP bromodomain inhibitors for the treatment of prostate cancer. Pharmacokinetic properties evaluation were analyzed by Medicilon. Liver microsomal stability assay were performed at Medicilon. Caco-2 permeability assay was analyzed by Medicilon.

Jul 05,2023

研究人員使用RZ-2994來表征抑制SHMT1/2在T細胞急性淋巴細胞白血病 (T-ALL) 中的作用，RZ-2994通過尊龍凱時定制合成

?Despite progress in the treatment of T-cell acute lymphoblastic leukemia (T-ALL) has limited treatment options, particularly in the setting of relapsed/refractory disease. Researchers used SHMT1/2 inhibitor RZ-2994 to characterize the effect of inhibiting SHMT1/2 in T-ALL. Loss of both SHMT1/2 is necessary for impaired growth and cell cycle arrest, with suppression of SHMT1/2 inhibiting leukemia progression. RZ-2994 also decreases leukemia burden in vivo. RZ-2994 was obtained from Medicilon. Medicilon offers a full range of chemical services covering all phases of your project. Customers can work with us either through FFS or FTE.

Jul 05,2023

研究人員開發(fā)了一種高特異性的CDC7抑制劑TAK-931作為臨床腫瘤治療劑，抗腫瘤藥效研究通過尊龍凱時進行

Cell division cycle 7 (CDC7) plays important roles in DNA replication. Researchers developed a highly specific CDC7 inhibitor, TAK-931, as a clinical cancer therapeutic agent. The antitumor efficacy studies in PDX models were performed at Medicilon. Medicilon has established a complete evaluation system for preclinical anti-tumor efficacy, and has more than 200 different types of tumor efficacy models.