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(xué)特性。作者感謝尊龍凱時對SLL-1206進(jìn)行的藥代動力學(xué)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(jìn)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(diào)節(jié)的內(nèi)質(zhì)網(wǎng)釋放系統(tǒng)揭示了意想不到的神經(jīng)元運輸途徑，Zapalog的合成通過尊龍凱時進(jìn)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(nèi)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(shè)計合成和評估用于治療前列腺癌的CBP溴結(jié)構(gòu)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(jìn)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(xì)胞急性淋巴細(xì)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(jìn)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.

Jul 05,2023

研究新型多靶點抗高血壓藥MT-1207的藥理學(xué)特性，評價MT-1207的結(jié)合抑制活性通過尊龍凱時進(jìn)行

Hypertension is a serious public health problem worldwide. MT-1207 is a chemical entity that has entered into clinical trial as antihypertensive agent. MT-1207 potently inhibits adrenergic α1A, α1B, α1D, and 5-HT2A receptors with Ki<1 nM in a panel of enzyme activity or radioligand binding assays. The binding inhibition activities of MT-1207 were evaluated by Medicilon.

Jul 05,2023

設(shè)計、合成和評估具有體內(nèi)抗炎活性的RIPK1抑制劑，PK研究通過尊龍凱時進(jìn)行

RIPK1 plays a key role in the necroptosis pathway that regulates inflammatory signaling and cell death in various diseases, including inflammatory and neurodegenerative diseases. Herein, researchers report a series of potent RIPK1 inhibitors, represented by compound 70. Compound 70 possesses favorable pharmacokinetic parameters with moderate clearance and good oral bioavailability in SD rat. The pharmacokinetic parameters were determined at Medicilon using male SD rats (3 rats per group, 4 groups).

Jul 05,2023

合成一類新型選擇性TNIK抑制劑并評估其抗結(jié)直腸癌作用，PK研究通過尊龍凱時進(jìn)行

The Traf2- and Nck-interacting protein kinase (TNIK) is a downstream signal protein of the Wnt/β-catenin pathway and has been thought of as a potential target for the treatment of colorectal cancer. SAR analysis leads to the identification of a number of potent TNIK inhibitors with Compound 21k being the most active one. Preliminary assessment for the pharmacokinetic properties of 21k was carried out through services provided by Medicilon.