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IND 100 Publications

Discovery of novel PDE4 inhibitors for the topical treatment of Psoriasis. The metabolic stability on mouse, rat, and human liver microsomes was determined by Medicilon

Psoriasis is a common immune-mediated skin disorder manifesting in abnormal skin plaques, and PDE4 is an effective target for the treatment of inflammatory diseases such as psoriasis. Researchers designed and synthesized the lead compound with high PDE4 inhibitory potency and remarkable metabolite profiles in liver microsomes. The metabolic stability on mouse, rat, and human liver microsomes was determined by Medicilon.

Discovery of novel PDE4 inhibitors for the topical treatment of Psoriasis. The metabolic stability on mouse, rat, and human liver microsomes was determined by Medicilon

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells. The pharmacokinetic study of the selective PAK4 inhibitor was carried out by Medicilon

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. 6-Ethynyl-1H-indole derivative 55 is a potent and selective PAK4 inhibitor (Ki=10.2 nM). Compound 55 is effective in the treatment of metastatic cancer. The pharmacokinetic study of Compound 55 was carried out by Medicilon.

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells. The pharmacokinetic study of the selective PAK4 inhibitor was carried out by Medicilon

Targeted protein degradation exemplified by PROTACs is an emerging strategy for drug discovery

Targeted protein degradation (TPD) exemplified by PROTACs is an emerging strategy for next generation drug discovery. Threonine tyrosine kinase (TTK) is a dual-specific protein kinase that catalyzes phosphorylation of both serine/threonine and tyrosine residues. Researchers designed and synthesized TTK PROTACs, which demonstrated reasonable pharmacokinetic profiles. All the pharmacokinetic studies were carried out by Medicilon, according to the protocols and guidelines of the institutional care and use committee.

Targeted protein degradation exemplified by PROTACs is an emerging strategy for drug discovery

Chlorpropamide has an anti-aging effect on worms and human lung fibroblast MRC-5 cells. Determination of Chlorpropamide bioavailability in mice was performed by Medicilon

Sulfonylureas exert their anti-diabetic effects by inhibiting K-ATP channels in the plasma membrane of islet β-cells. Chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to produce mtROS as a pro-longevity signal. Chlorpropamide has an anti-aging effect on worms and human lung fibroblast MRC-5 cells. Determination of Chlorpropamide bioavailability in mice was performed by Medicilon.

Chlorpropamide has an anti-aging effect on worms and human lung fibroblast MRC-5 cells. Determination of Chlorpropamide bioavailability in mice was performed by Medicilon

BRD4 inhibitors can be used for the treatment of kidney fibrosis. ZLD2218 exhibited the potent inhibitory activity against BRD4. PK analysis of of ZLD2218 were analyzed by Medicilon

Uncovering new therapeutics for kidney fibrosis hold promise for chronic kidney disease (CKD). BRD4 inhibition ameliorated kidney injury and fibrosis. ZLD2218 exhibited the potent inhibitory activity against BRD4, with the IC50 value of 107 nM. Pharmacokinetic analysis of of ZLD2218 were analyzed by noncompartmental methods using Phoenix WinNonlin 7.0 (Accomplished by Medicilon).

BRD4 inhibitors can be used for the treatment of kidney fibrosis. ZLD2218 exhibited the potent inhibitory activity against BRD4. PK analysis of of ZLD2218 were analyzed by Medicilon

Immune checkpoint blockade therapies have changed the paradigm of cancer therapies. In vivo studies for anti-PD-1 antibody across 23 syngeneic tumor models were performed by Medicilon

Immune checkpoint blockade therapies have changed the paradigm of cancer therapies. Reseachers performed in vivo screening for anti-PD-1 therapy across 23 syngeneic tumor models and found that CT-26 and Colon 26, which are murine colorectal carcinoma derived from BALB/c mice, showed different sensitivity to anti-PD-1. In vivo studies for anti-PD-1 antibody across 23 syngeneic tumor models were performed by Medicilon.

Immune checkpoint blockade therapies have changed the paradigm of cancer therapies. In vivo studies for anti-PD-1 antibody across 23 syngeneic tumor models were performed by Medicilon

PDE1 is a promising drug target closely related to central and peripheral diseases

Phosphodiesterase-1 (PDE1) is a promising drug target closely related to central and peripheral diseases. Compound 2j with the IC50 of 21 nM against PDE1B, shows good metabolic stability in the rat liver microsomes. Stability test in the rat liver microsomes were performed by Medicilon.

PDE1 is a promising drug target closely related to central and peripheral diseases

SKLB-YTH-60 ameliorates inflammation and fibrosis in Bleomycin-induced lung fibrosis mouse models. The in vivo pharmacokinetic study of YTH‐60 was performed by Medicilon

Idiopathic pulmonary fibrosis is a chronic and lethal lung disease associated with fibroblast activation, myoblast proliferation and extracellular matrix deposition. SKLB-YTH-60 was developed through computer-aided drug design, de novo synthesis and high-throughput screening. YTH-60 has obvious anti‐proliferative activity on fibroblasts and A549 cells. YTH-60 has an acceptable oral bioavailability and appropriate eliminated half-life time. The in vivo pharmacokinetic study of YTH‐60 was performed by Medicilon.

SKLB-YTH-60 ameliorates inflammation and fibrosis in Bleomycin-induced lung fibrosis mouse models. The in vivo pharmacokinetic study of YTH‐60 was performed by Medicilon

Researchers successfully discovered an orally available PROTAC degrader SIAIS164018 with orally bioavailable and well tolerated in vivo. PK and MTD assays were performed by Medicilon

PROTAC is an attractive technology in drug discovery. Researchers successfully discovered an orally available PROTAC degrader SIAIS164018 which degrades not only ALK or mutant EGFR but also oncoproteins involved in metastasis. SIAIS164018 is orally bioavailable and well tolerated in vivo. Pharmacokinetic and maximal tolerated dose (MTD) assays were performed by Medicilon.

Researchers successfully discovered an orally available PROTAC degrader SIAIS164018 with orally bioavailable and well tolerated in vivo. PK and MTD assays were performed by Medicilon

Discovery and preclinical development of orally active and highly selective follicle stimulating hormone receptor agonists. Toxicological evaluations in both rat and dog were performed by Medicilon

TOP5300 is an orally active follicle stimulating hormone receptor allosteric agonist that provides a preferred treatment for over 16 million infertile women of reproductive age in low complexity methods or in high complexity methods. TOP5300 was evaluated in standard ADME, including Cytochrome P450 inhibition, clearance and pharmacokinetic profiles. Toxicological evaluations were performed in both rat and dog as the second species according to the guidance from FDA. These assays were performed by Medicilon.

Discovery and preclinical development of orally active and highly selective follicle stimulating hormone receptor agonists. Toxicological evaluations in both rat and dog were performed by Medicilon

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