R&D
Developing the drugs that elevate the patients’ quality of life
Platform
New drug discovery platform Ⅰ
Molecular design
- Efficient in-silico design of anti-cancer agents utilizing X-ray crystal structure of target proteins and molecular docking
- Creative construction of molecular agents with high activity and selectivity based on the insight into the binding modes of existing drugs
Target-
Focused Drug
Discovery
Focused Drug
Discovery
-
Target Analysis
- Building in-house database using crystal structures
- Establishing unique strategies based on R&D outcomes
-
Design
- Effective drug design based on in-house expertise
- Simulation via molecular dockings
-
Synthesis
- Analysis of docking and crystal structures
- Synthesis of strictly selected compounds
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Bioassay
- Biochemical assay
- Cell-based assay
- In vivo efficacy study
New drug discovery platform Ⅱ
Discovery of orally bioavailable PROTACs
- Many ongoing studies on PROTAC show difficulty in oral absorptions
- “The real bottleneck is making PROTACs orally bioavailable. They have a higher molecular weight (0.7–1.1 kDa), more hydrogen bond donors and a larger polar surface area than typical small molecules, all factors that work against gut permeability." Nature Biotechnology 40, 12-16 (2022)
- Therapex has strong expertise on enhancing the oral absorption of compounds with MW of 500~900 that violate the Rule of 5.
TPD (Target Protein Degrader)
Oral TPD Descriptors
Molecule
MW
HBD
ClogP
TPSA
NRB
Ro5 Viol.
ARV-110
812
2
4.3
180
3
2
ARV-471
724
2
6.8
96
7
2
Examlple Oral Degrader
909
3
7.5
167
13
3
Median PROTAC-DB*
993
4
4.9
223
20
3
Median Oral HMW**
817
4
3.8
209
17
3
* PROTAC-DB https://doi.org/10.1093/nar/gkaa807
** High molecular weight (HMW) from Tinworth 2020 and Shultz 2019 (MW > 600)
Ro5: MW ≤ 500, HBD ≤ 5, HBA≤10, logP≤5, PSA ＜140, NRB＜10
** High molecular weight (HMW) from Tinworth 2020 and Shultz 2019 (MW > 600)
Ro5: MW ≤ 500, HBD ≤ 5, HBA≤10, logP≤5, PSA ＜140, NRB＜10