ABPP and Target Validation

In the context of Activity-Based Protein Profiling (ABPP), which of the following BEST describes the focus of Pillar 3?

Why is selectivity greater than 100-fold emphasized in the context of quality probes for target validation?

What is the PRIMARY aim of "proof of phenotype perturbation" (Pillar 4) in cell-based target validation?

Why is it important to ensure that probe exposures are commensurate with the on-target activity during target validation?

Which factor is LEAST relevant when defining a quality probe for target validation, according to the provided information?

According to the information provided, what is the primary mechanism by which Ifetroban is believed to reduce metastasis?

In the context of TNBC (Triple-Negative Breast Cancer) metastasis, what types of treatment with Ifetroban have demonstrated a significant reduction in metastasis in spontaneous mouse models?

Besides TNBC, in which other cancer models and cancer types has Ifetroban demonstrated a significant reduction in metastasis?

How does Ifetroban affect circulating tumor cells (CTCs) in relation to the host immune response, according to the 4T1 mouse model data?

What effect does Ifetroban have on the ability of tumor cells to interact with the vascular epithelium and platelets?

What is the role of P-selectin in the context of Ifetroban's impact on metastasis, according to the information?

Based on the concept of target validation using chemical probes, what is the primary purpose of using fully profiled chemical probes?

Ifetroban is identified as a thromboxane receptor inhibitor. Considering its impact on metastasis, what is the most likely mechanism of action related to this inhibition?

In the context of drug development, what is the primary goal of drug repositioning?

Which of the following is NOT a criterion used to narrow down the list of potential drugs for repurposing, according to the presented methodology?

What is the significance of having access to clinical data before the first dose of an investigational new drug is given, according to the BioVU approach?

In the context of drug development, what is often the primary reason for the failure of drug programs in phase II clinical trials?

Which aspect is NOT one of the 'four pillars' crucial for successful target validation in drug development?

What does PheWAS (Phenome-Wide Association Study) contribute to the drug repositioning process described?

The PheWAS analysis revealed an association between metastatic recurrence and a specific Single Nucleotide Polymorphism (SNP) in which receptor?

What is the importance of confirming that a probe achieves pharmacologically relevant concentrations inside cells, according to the text?

What is the most likely explanation for mismatches between the biochemical activity of a probe and its whole-cell activity?

If a patient has the Threonine 399 to Alanine (T399A) mutation in the Thromboxane A2 Receptor (TBA2), and this is associated with metastatic recurrence, what type of drug would be most appropriate, according to the information provided?

In the context of assessing functional pharmacology of a chemical probe, what type of measurement is typically used?

What is the functional consequence of the T399A mutation in the Thromboxane A2 Receptor (TBA2)?

In the context of drug repositioning for metastatic recurrence associated with the T399A mutation, how does understanding the mechanism of action of potential drug candidates aid in the selection process?

A research team observes that a kinase inhibitor shows excellent activity against the purified kinase enzyme in vitro, but demonstrates minimal effect in cell-based assays. What is the MOST probable cause for this discrepancy?

A research group is developing a chemical probe to modulate a specific intracellular protein. They find that the probe binds strongly to the target protein in vitro. According to the four pillars of target validation, what is the NEXT essential step to validate that the probe is useful in a biological setting?

In drug development, if a chemical probe shows appropriate exposure at the site of action and confirms target engagement, which additional validation step is crucial to ensure the drug's potential efficacy?

In the context of validating a target using chemical probes, what is the primary goal of assessing 'exposure at the site of action' (Pillar 1)?

Which analytical technique is most commonly used to detect the presence of a small molecule probe inside a cell or cell organelle when assessing 'exposure at the site of action'?

What is the main purpose of 'Target Engagement' (Pillar 2) in the context of using chemical probes for target validation?

The in-cell thermal shift assay is used in the 'Target Engagement' pillar. What principle does this assay rely on to demonstrate target engagement?

In the context of chemical probe validation, what does 'Proof of pharmacology' (Pillar 3) primarily assess?

Which of the following is an example mentioned in the text of a proximal biomarker that might be assessed in 'Proof of pharmacology' (Pillar 3)?

What is the main challenge in 'Proof of phenotype perturbation' (Pillar 4) when using chemical probes for target validation?

Why is it important to rule out nonspecific cell death in the early stages of 'Proof of phenotype perturbation'?

Why might using probes at concentrations exceeding their selectivity window lead to inaccurate conclusions in biology experiments?

What role do medicinal chemists play when working with probes?

What is the purpose of using an inactive enantiomer as a control in experiments involving chemical probes?

Which factor should be carefully considered when using probes in cell biology experiments to avoid misleading results?

In chemical probe design, what is the significance of 'multiple active and selective chemical classes'?

Why is it important to consider the structure of a chemical probe?

How do analytical chemists contribute to the use of chemical probes?

What is the primary reason to evaluate the potency of a chemical probe?