Payload Star - Exatecan in ADC field ChemExpress scaling-up synthetic strategy of Exatecan
In August, FDA has approved AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) for the treatment of two extended indications: HER2-low breast cancer and non-small cell lung cancer (NSCLC). This is the third cancer type approved by the FDA for treatment with Enhertu.
Enhertu's impressive efficacy in treating cancer has made Exatecan (DXd precursor) getting more popular. However, how to realize the lower cost and more efficient synthesis of Exatecan in large scale is still the thing we are pursuing for our customers.
Fig.1 DXd is the Exatecan derivatives
Challenges
Fig.2 RoS of Key Intermediate and Exatecan-WO2019044946A1/ US11318212B2/ AU2018327170B2
■ Usage of noble metals (Pd), making the process expensive for scaling-up
■ High pressure hydrogenation, making the process risky
■ 10 steps, 5.3% overall yield
Solutions
Fig.3 Chemexpress RoS of Key Intermediate and Exatecan-WO2022000868A1/ CN111470998B/ CN111875517A
√ Innovative synthesis of intermediate A , avoiding infringing existing patents
√ Only 4 steps are required to obtain the key intermediate from inexpensive commercial SM and the total yield reach to 43%
√ No noble metal catalyzed coupling reaction or high-pressure hydrogenation is needed, making the synthesis process less expensive and suitable for large scale manufacturing
√ 8 steps, 15% overall yield
Our Exatecan Production Capacity
√ Economic process, low cost and fast turn around time for batch production.
√ Quality:≥ 99% purity, ≥98% ee, ≥ 99% de, any single impurity < 0.1 %
√ Regular storage of multiple kilograms of GMP Exatecan mesylate, and non-GMPExatecan and intermediates.
√ Successfully registered in the U.S. FDA for DMF code: MF036708
ChemExpress Capacity in ADC Small Molecules Field:
√ In-stock inventory
√ Kilogram GMP supply of compounds
√ CMC service to support IND/NDA filing in multiple countries
√ One-stop CDMO services