Drug Discovery Solutions for Targeting Lysosomal Calcium Signaling

Background of Drug Discovery Targeting Lysosomal Calcium Signaling

Intracellular calcium ions (Ca²⁺) are the most abundant second messengers in the body and have a variety of roles in basic cellular physiology including gene expression, cell cycle control, cell motility, autophagy and apoptosis. In addition to acting as a cellular recycling centre, lysosomes are increasingly recognised as an important intracellular Ca²⁺ reservoir, providing Ca²⁺ to regulate many cellular processes. Lysosomes also talk to other organelles through the release and uptake of Ca²⁺. Autophagy is particularly important in lysosomal Ca²⁺-dependent processes, as it is associated with many human diseases, including cancer. There is growing evidence that intracellular Ca²⁺ homeostasis is altered in cancer cells and that this alteration is involved in tumourigenesis, angiogenesis, progression and metastasis. Targeting derailed Ca²⁺ signaling in cancer therapy has become an emerging area of research.

Fig. 1. Targeting calcium signaling in cancer therapy. (Cui C, et al., 2017)

Solutions

Intracellular Ca²⁺ homeostasis is controlled by a network of various Ca²⁺ channels and transport proteins. To proliferate at high rates, increase cell motility and invasion, evade death, fool immune attack or generate new blood vessels, tumours reshape their Ca²⁺ signalling network. Our scientists have identified lysosomal Ca²⁺ channels and transporter proteins as highly relevant targets for therapeutic interventions in cancer to develop appropriate targeting measures. Our goal is to help you design compounds that can target Ca²⁺ channels/transport proteins/pumps to disrupt normal Ca²⁺ signalling for cancer therapy.

Based on our understanding of the intracellular Ca²⁺ signalling network in cancer, CD BioSciences is committed to providing our global customers with strategies to target lysosomal calcium signalling in cancer. We offer a broad range of lysosomal calcium signalling targets.

Targeting IP₃Rs-Endoplasmic Reticulum Ca²⁺ Release Channels

IP₃R1, IP₃R2 , IP₃R3.

Targeting Ca²⁺-ATPase

SERCA2, SERCA3, SPCA1, SPCA2, PMCA1, PMCA2, PMCA2.

Targeting Plasma Membrane Ca²⁺ Channels

Voltage-gated Ca²⁺ channels: Cav1.2, Cav2.3, Cav3.1, Cav3.2.

TRP channels: TRPC1, TRPC3, TRPC6, TRPM1 , TRPM7, TRPM8, TRPV1, TRPV2, TRPV4, TRPV6.

Orai and STIM: Orai1, Orai3, STIM1 , STIM2.

Purinoceptors: P2X3, P2X5, P2X7, P2Y2, P2Y4.

Targeting the Mitochondrial Ca²⁺ Unidirectional Transporter

MCU.

Based on the wealth of potential targets we have developed for the intracellular Ca²⁺ signalling network, we are also focusing on drug design with potential and specificity for selective inhibitors or modulators. We seek to design known compounds or antibodies against the above mentioned Ca²⁺ channels/transporters/pumps associated with cancer. Our services support these compounds or antibodies in pre-clinical studies.

• Ca²⁺-ATPase inhibitors.
• Voltage gated Ca²⁺ channel inhibitors.
• TRP channel regulators.
• Orai inhibitors.

Why Choose Us

• Selection of multiple strategies for the Ca²⁺ toolkit in cancer.
• Structure-based rational design of more efficient, specific and less off-target compounds for Ca²⁺ channels/transporters/pumps.
• Rapid experimental process to deliver results at an economical cost.
• Collaborate with experienced international technical staff.

CD BioSciences can meet any reasonable needs of our clients, taking time and budget into consideration for you. Our aim is to be customer-centric and to provide the highest quality services to customers. Our customer service representatives are enthusiastic and trustworthy 24 hours a day, 7 days a week. If you are interested in our services, please feel free to contact us for more information or a detailed discussion.

Reference

1. Cui C, Merritt R, Fu L, et al. (2017) Targeting calcium signaling in cancer therapy[J]. Acta pharmaceutica sinica B. 7(1): 3-17.