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Integrated Solutions

Deeply integrate R&D experience, constantly climb the peak of R&D technology, and build an integrated innovation service platform for new drug R&D.

PROTAC Drug Discovery Research Platform

Medicilon gathers the popular POI ligands and multiple tissue types of E3 ligase ligands, in addition of established a linker library containing hundreds of linking molecules.
Medicilon diamond icon.pngPROTAC technology has a unique mechanism
Medicilon diamond icon.pngAdvantages of PROTAC Technology in Drug Development
Medicilon diamond icon.pngIntroduction of Medicilon PROTAC Services
  • In Vitro Screening of PROTAC-POI
    Cytotoxicity Assay (CCK-8 & CTG)
    Mechanism detection by proliferation inhibition tests.

    Percentage-degradation-of-HiBiT-IRAK4-in-HiBiT-IRAK4-overexpression-OCI-LY10-cells.png

    Percentage degradation of HiBiT-IRAK4 in HiBiT-IRAK4 overexpression OCI-LY10 cells

    Western Blot(WB)
    Conduct WB to test target protein degradation ability and analyze DC50.

    Western-blot-of-anti-IRAK4-on-OCI-LY10-cells-treated-with-IRAK4-degrader-1.png

    Western blot of anti-IRAK4 on OCI-LY10 cells treated with IRAK4 degrader-1

    Pomalidomide-(CRBN-binder)-competition-experiment-show-that-IRAK4-degrader-1--degrades-IRAK4-through-CRBN.png

    Pomalidomide (CRBN binder) competition experiment show that IRAK4 degrader-1  degrades IRAK4 through CRBN

    MG132-inhibition-experiment-show-that-IRAK4-degrader-1-degrades-IRAK4-through-proteasome-pathway.png

    MG132 inhibition experiment show that IRAK4 degrader-1 degrades IRAK4 through proteasome pathway

    Tumor cell proliferation inhibition effect test

    Growth-inhibition-effect-of-IRAK4-degrader-1-on-OCI-LY10-cells.png

    Growth inhibition effect of IRAK4 degrader-1 on OCI-LY10 cells

    ACBI1-(BRM-degrader)-degrades-BRM-in-dose-response-manner.png

    ACBI1 (BRM degrader) degrades BRM in dose response manner

  • In Vivo Efficacy Tests of PROTAC-POI
    CDX Mouse Tumor Model

    Cancer TypeOrthotopic ModelOrthotopic Model (Luc Cell Line)
    Brain CancerU87-MGU87-MG-luc
    Lung CancerNCI-H1650, A549, NCI-H1975, NCI-H460, LLC1A549-luc, LLC1-luc,NCI-H1975-luc
    Colon CancerHCT-116, LoVoHT29-luc
    Gastric CancerHs 746T
    Pancreas CancerMia-Paca 2Mia-Paca 2-luc
    Breast CancerMDA-MB-2314T1-luc
    Ovarian CanerSK-OV-3SK-OV-3-luc
    Prostate CancerPC3PC-3-luc
    Renal CancerA498
    Bladder CancerUM-UC-3
    MelanomaB16-F10-luc
    Liver CancerH22
    Bone Cancer
    PDX Mouse Tumor Model

    Cancer TypeCell Lines
    Colon Cancer                                PDXM-008C, PDXM-016C, PDXM-020C, PDXM-021C, PDXM-057C, PDXM-060C,    PDXM-075C, PDXM-076C, PDXM-087C, PDXM-104C, PDXM-095C, PDXM-084C, PDXM-072C,    PDXM-069C, PDXM-057C, PDXM-015C, PDXM-002C,
    Lung Cancer                                PDXM-054Lu, PDXM-050Lu, PDXM-047Lu, PDXM-053Lu, PDXM-028Lu,
    Gastric CancerPDXM-092Ga, PDXM-091Ga,
    Breast CancerPDXM-201B, PDXM-202B, PDX-203B
    Liver CancerPDXM-211Li, PDXM-212Li
    Pancreas CancerPDXM-221Pa, PDXM-222Pa
    Bladder CancerPDXM-231U, PDXM-232U
    LymphomaPDXM-241Ly, PDXM-242Ly
  • Integrated Preclinical Services
    We can further proceed the R&D of the potential PROTAC molecule by facilitating our integrated preclinical services including CMC services, DMPK studies, safety evaluation, etc.
    The pharmacokinetics (PK) data show that five highly potent androgen receptor (AR) degraders achieve good to excellent overall PK profiles with ARD-2128 being the best compound. ARD-2128 has low clearance (1.2 mL/min/kg) and a moderate to high steady-state volume of distribution (Vss) of 2.7 L/kg. ARD-2128 (2 mg/kg, i.v.) and ARD-2128 (5 mg/kg, p.o.) both have long half-lives following intravenous and oral administration with the T1/2s of 27.6 h and 18.8 h, respectively. ARD-2128 (5 mg/kg) achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity.
     Summary of PK Data for Five Compounds in Male ICR Mice
    Summary of PK Data for Five Compounds in Male ICR Mice[1]
    The plasma and microsomal stability data show that ARD-2128 has excellent plasma and microsomal stability in in mouse, rat, dog, monkey, and humans.
    Evaluation of ARD-2128 for Its Plasma Stability and Microsomal Stability
    Evaluation of ARD-2128 for Its Plasma Stability and Microsomal Stability[1]
    References:
    [1].Xin Han,et al. Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer.J Med Chem. 2021 Sep9;64(17):12831-12854. doi: 10.1021/acs.jmedchem.1c00882. Epub 2021 Aug 25
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