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Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19.

Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill & Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories.

In this paper we describe strategies used to prioritize thousands of β-lactams from multiple companies into a small test set for further characterization.
In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-lactamase inhibitor.
One potent cephaloporin was active in Mtb-infected mice.

The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents.

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The 12^th edition of our Drug Discovery Update (DDup) provides insights into exciting new developments in 3D cell models including microtissues, organoids and organ-on-a-chip technology.

In this edition, it covers:

an introduction to 3D cellular models
- the need for better models to improve translation from in vitro to in vivo
- the relevance of 3D cellular models to kidney disease modelling and drug induced toxicity prediction
an overview of Evotec's 3D in vitro platforms
- glomerulus-on-a-chip to study kidney disease
- kidney organoids to study polycystic kidney disease
- organ microtissues to predict drug-induced toxicity
interviews with experts Dr Christodoulos Xinaris, Dr Reiner Class, Dr Magali Ferro and Dr Stephanie Ryder

LEARN MORE

Science Pool

An Overview of Safety Assessment Services

Read about 3D Cellular Models in Prediction of Tox and Kidney Disease

Free Guide: Everything you Need to Know about ADME

Whitepaper: An Integrated Approach to Drug Abuse Liability

Want to Know More about Transcriptomics in Tox Prediction?

Find the Fastest Route to the Clinic

Read our Pathology Fact Sheet

Learn More about Toxicology in our Science Pool

Identification of β-Lactams Active Against Mycobacterium Tuberculosis

3D Cell Models DDup #12