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1. Clear MoA
a) Orexin A and orexin B are hypothalamic neuropeptides.
b) Orexin A and B combine with OX1R and OX2R to activate Gq PLC/PKC/ERK, Gs/AC/cAMP/PKA/ERK (and/or CREB, p38 MAPK) and Gi pathways.
c) The OX2R signal through Gq/PLC/PKC pathway is stronger than OX1R signal.
d) Gq/PLC/PKC pathway triggers PKC mediated calcium influx and releases intracellular calcium storage. The increase of calcium level makes neurons continuously excited, thus maintaining wakefulness.
2. Efficacy—Compared with Zopiclone
a) This asset has a short incubation period and takes effect quickly. The duration of the effect was moderate, and the effect basically disappeared after 8 hours, with little risk of side effects.
b) It has no obvious influence on the process of shallow sleep (REM), which is conducive to the maintenance of normal sleep cycle and healthy sleep.
c) It can promote deep (NREM) sleep and light (REM) sleep, and reduce the amount of sleep awakening.
Fig. 1 Total sleep duration ratio in rats from 0-24 hours
3. Safety—Compared with Suvorexant
It has higher in vitro activity and target selectivity than Suvorexant, with better hERG and CYP values than Suvorexant.
4. Indication extension potential
It can further develop more sleep and cognitive related indications, including patients with sleep disorders in the population with other specific diseases.
5. Phase II summary
a) Induced a dose-response improvement on sleep efficiency in subjects with insomnia. had favorable safety profiles in the dose range studied.
b) Had no obvious CNS adverse events compared with placebo, indicating fewer next-day residual effects.
Fig. 2 Dose-related improvement in SE on D1/2 and D13/14.
Fig.3 Sleep Efficiency (%SE) of Dual Orexin Receptor Antagonists
1. Asset type: Orexin Receptor Antagonist (OX1R and OX2R)
2. Indication: Insomnia Disorder
3. Research phase: Phase 3 (China)
4. Administration route: oral (20 mg/40 mg)
5. Cooperation demands: License-out or co-development
6. Research progress：
1) The asset has higher in vitro activity and target selectivity than Suvorexant, and both hERG and CYP values are better than Suvorexant.
2) The asset is currently in the phase III clinical trial in China, and will complete the phase III clinical trial and apply for production in Q2 2023.
3) The asset can further develop more sleep and cognitive related indications, including sleep disorders in people with other specific diseases.
ACROBiosystems offers a wide selection of Matrigengel basement membrane extracts. Different versions – including phenol red-free, high concentration, iPSC culturing, organoid culturing – are all available for your specific needs to support 3D cell culture!
To enable antibody characterization methodsACROBiosystems has developed a series of enzymes.such as ldeS, SpeB, EndoH, and Endo S proteases, toassist with the characterization of antibodies and theirrelated post-translational modifications (PTMs)
ComboX is a new brand of ACROBiosystems. ComboX products include our Streptavidin series products, coated plates, isotype controls for antibody and fusion protein drug research, and general-purpose antibodies.
50+ targets designed for CAR detection, including PE/FITC/biotin labeled proteins. The key reagents for CD19 and BCMA were FDA DMF filed which can support your IND, NDA and BLA process.
ACROBiosystems developed a series of GMP grade cytokines under the GMP grade quality management system. Those products are all suitable for T/NK cell generation, activation, and proliferation in cell therapy research.
GMP grade cytokines, reagents for cell activation, gene edition, DNA/RNA removal, etc. Particularly focus on product design, quality control and solution-based support to link each phase of your cell and gene therapy journey.
Full length multi-pass TPs with stabilized structure and high bioactivity for immunization, antibody screening, cell based assay and CAR detection, including hot CD20, Claudin 18.2， CD133, GPRC5D，CCR8, CCR5, etc.
A series of immune checkpoints including classic co-inhibitory and co-stimulatory receptors. The comprehensive catalog contains 100+ targets with various species and tags, and the high-quality proteins are in good batch-to-batch consistency.
To meet the needs of ADCs development, ACROBiosystems can provide: A variety of high-quality target proteins; MMPs/Cathepsin/uPA for cleavable linker; Anti-payload antibodies & anti-idiotypic antibodies for immunogenicity and PK analysis; SPR/BLI analytical and ADA development service.
Comprehensive collection of Fc receptor proteins, including their common variants, which can help expedite your antibody development.
Comprehensive cytokine targets including interleukins, growth factors, chemokines, TNFs, etc. are expressed by HEK293 to ensure their natural structure. Their high purity is verified by SDS-PAGE/HPLC/SEC-MALS and high bioactivity is verified by ELISA/SPR/BLI.
Aneuro is ACROBiosystems brand focused on neuroscience research, providing high-quality important proteins including therapeutic and diagnostic research proteins, PFFs and recombinant neuro factors, etc. to advance neuroscience research.
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