Table 1.

MARCKS Translational Research Summary: Model Types and Significant Findings

	Model/Cell Type	Investigational Strategy to Inhibit MARCKS Function	Significant Finding(s) for MARCKS Function	References
Acellular models	Computational models	ED peptide	MARCKS sequesters PIP2 through electrostatic interactions	53
	Lipid models	ED peptide	MARCKS sequesters PIP2/PIP3, regulates PIP2 availability as PI3K substrate	54, 60, 61
Cells in vitro	Neutrophils	N-terminal peptide (MANS), BIO-11006	MARCKS involved in directed migration, adhesion, respiratory burst, cytokine production, and degranulation	8, 21, 93, 94, 100
	Macrophages	MANS, siRNA	MARCKS involved in directed migration and cytokine production	13, 96
	Mast cells	ED peptide	MARCKS involved in degranulation	130
	Fibroblasts	MANS, siRNA	MARCKS involved in directed migration	15, 16
	Stem cells	MANS	MARCKS involved in directed migration	95
	Airway goblet cells	MANS, BIO-11006	MARCKS involved in mucin secretion	18, 92, 97, 100, 108–111, 113–115
	Vascular smooth muscle cells	siRNA, mutated protein expression	MARCKS involved in adhesion and α5β1 integrin function	138
	Endothelial cells	siRNA	MARCKS involved in directed migration	63, 139
	Lung cancer cells	MANS, siRNA, BIO-11006, ED peptide, mutated protein expression	NSCLC cells: elevated p-MARCKS expression, MARCKS involved in cancer cell migration, MARCKS enhances radiation sensitivity	12, 104, 141–143, 163
In vivo, animal models	Mouse mucus hypersecretion/allergic inflammation models	MANS, BIO-11006	MARCKS involved in airway mucin secretion and inflammation	17, 20, 98, 107
	Mouse ALI/ARDS models	BIO-11006, MANS	MARCKS pulmonary inflammation and ALI	22, 23
	Mouse lung cancer models	MANS, BIO-11006, ED peptide	MARCKS involved in metastasis and tumor growth	12, 99, 164
Human clinical trials	Healthy volunteers	Inhaled BIO-11006	Safe pulmonary and systemic profile	Clinical Trials BIM-CL-001, BIM-CL-002
	Chronic bronchitis	Inhaled BIO-11006: 172 subjects with COPD, double-blind, placebo-controlled, multicenter dose escalation study for 21 d	75 mg twice daily increased proportion of clinically significant FEV1 response	136, Clinical Trial BIM-CL-003
	ARDS	Inhaled BIO-11006: 40 ventilated ICU patients, randomized, placebo- controlled trial	Expected 2019	Clinical Trial BIM-CL-005
	NSCLC	Inhaled BIO-11006: randomized, SOC controlled trial	Expected 2019	Clinical Trial BIM-NSCLC-001

Definition of abbreviations: ALI = acute lung injury; ARDS = acute respiratory distress syndrome; COPD = chronic obstructive pulmonary disease; ED = effector domain; ICU = intensive care unit; MANS = myristoylated N-terminal sequence; MARCKS = myristoylated alanine-rich C kinase substrate; NSCLC = non–small cell lung cancer; PIP₂ = phosphatidylinositol 4,5-bisphosphate; PIP₃ = phosphatidylinositol (3,4,5)-trisphosphate; p-MARCKS = phosphorylated MARCKS; SOC = standard of care.