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Preclinical systemic pharmacokinetics, dose-proportionality, and CNS distribution of the ATM inhibitor WSD0628, a novel radiosensitizer for the treatment of brain tumors [Metabolism, Transport, and Pharmacogenetics]

ASPET

Radiation therapy, a standard treatment option for many cancer patients, induces DNA double strand breaks (DSBs), leading to cell death. The objective of this study was to evaluate the systemic pharmacokinetics and mechanisms that influence the CNS distribution of WSD0628, a novel and potent ATM inhibitor, in the mouse.

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Translational pharmacokinetic-toxicodynamic model of myelosuppression for dose optimization in combination chemotherapy of capecitabine and oxaliplatin from rats to humans [Drug Discovery and Translational Medicine]

ASPET

XELOX therapy, which comprises capecitabine and oxaliplatin, is the standard first-line chemotherapeutic regimen for colorectal cancer. Mathematical modeling combining pharmacokinetics (PK) and toxicodynamics (TD) is a promising approach for optimizing dosing strategies and reducing toxicity.

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Factors influencing the Central Nervous System (CNS) distribution of the ATR inhibitor elimusertib (BAY1895344): Implications for the treatment of CNS tumors [Metabolism, Transport, and Pharmacogenetics]

ASPET

GBM has a poor prognosis despite aggressive treatment, in part due to lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. These observations can guide further exploration of elimusertib for the treatment of GBM, or other CNS tumors.

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The future of lymphoma treatment

Drug Target Review

We use hydrophilic linkers, which prevent ADC aggregation and generate highly stable ADCs, in combination with a unique attachment site on the antibody to create ADCs that retain pharmacokinetic properties similar to the original unconjugated antibody. This helps to maximize the targeted payload delivery to tumor cells.

Treatment 115
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Pramlintide an Adjunct to Insulin Therapy: Challenges and Recent progress in delivery [Minireview]

ASPET

However, Pramlintide an adjunct to insulin therapy, enhances glucagon suppression and thereby offers improved glycaemic control. Although clinical benefits of Pramlintide are well reported, there still exists a high patient resistance for the therapy as separate injections for Pramlintide and insulin are required to be administered.

Therapies 100
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Breakthrough drug candidates and cancer treatment innovations

Drug Target Review

It also displayed favourable pharmacokinetics (PK) and is well tolerated in non-human primates (NHP) at exposure levels above those projected to be efficacious. It also supports the argument for developing ZW171 for the treatment of other MLSN-expressing solid tumours.

Treatment 101
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STAR-0215 is a Novel, Long-Acting Monoclonal Antibody Inhibitor of Plasma Kallikrein for the Potential Treatment of Hereditary Angioedema [Drug Discovery and Translational Medicine]

ASPET

A single subcutaneous dose of STAR-0215 ({greater than or equal to} 100 mg) was predicted to be active in patients for 3 months or longer, based on simulations using a minimal physiologically based pharmacokinetic (mPBPK) model.

Treatment 100