Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

A Ternary Neural Network Computing-in-Memory Processor With 16T1C Bitcell Architecture

A highly energy-efficient Computing-in-Memory (CIM) processor for Ternary Neural Network (TNN) acceleration is proposed in this brief. Previous CIM processors for multi-bit precision neural networks showed low energy efficiency and throughput. Lightweight binary neural networks were accelerated with CIM processors for high energy efficiency but showed poor inference accuracy. In addition, most previous works suffered from poor linearity of analog computing and energy-consuming analog-to-digital conversion. To resolve the issues, we propose a Ternary-CIM (T-CIM) processor with 16T1C ternary bitcell for good linearity with the compact area and a charge-based partial sum adder circuit to remove analog-to-digital conversion that consumes a large portion of the system energy. Furthermore, flexible data mapping enables execution of the whole convolution layers with smaller bitcell memory capacity. Designed with 65 nm CMOS technology, the proposed T-CIM achieves 1,316 GOPS of peak performance and 823 TOPS/W of energy efficiency

A Ternary Neural Network Computing-in-Memory Processor with 16T1C Bitcell Architecture

A highly energy-efficient Computing-in-Memory (CIM) processor for Ternary Neural Network (TNN) acceleration is proposed in this paper. Previous CIM processors for multi-bit precision neural networks showed low energy efficiency and throughput. Lightweight binary neural networks were accelerated with CIM processors for high energy efficiency but showed poor inference accuracy. In addition, most previous works suffered from poor linearity of analog computing and energy-consuming analog-to-digital conversion. To resolve the issues, we propose a Ternary-CIM (T-CIM) processor with 16T1C ternary bitcell for good linearity with compact area and a charge-based partial sum adder circuit to remove analog-to-digital conversion that consumes a large portion of the system energy. Furthermore, configurable data mapping enables execution of the whole convolution layers with smaller bitcell memory capacity. Designed with 65 nm CMOS technology, the proposed T-CIM achieves 1,316 GOPS of peak performance and 823 TOPS/W of energy efficiency