Table 2 Small molecule inhibitors and biologics used to target macropinocytosis

EIPA

Na⁺/H⁺ exchange

Impact on submembranous alkaline pH

Preclinical

Not available (N/A)

[106, 107]

Gefitinib

EGFR

Inhibit the macropinocytosis pathway

FDA Approval, Phase 2 (completed, NCT02804776)

Non-small cell lung Cancer, Non-small cell lung Cancer

[108]

GCS-100

Galectin-3

Inhibit the macropinocytosis pathway

Phase 2 (completed)

Chronic kidney disease

[109, 110]

TBOPP

DOCK1

Repress DOCK1-mediated macropinocytosis

Preclinical

N/A

[102]

Wortmannin, LY294002

PI3K

Inhibit PI3K signaling pathway

Preclinical

N/A

[100, 111]

Torin1 and AZD2014

mTOR

Suppress proteins scavenging

Preclinical

N/A

[112, 113]

Sepantronium bromide (YM155)

AMPK

Block mTORC1

Phase 2 (completed)

Non-Hodgkin’s lymphoma

[105, 114]

Blebbstatin

myosin II

Blocks the myosin heads in a products complex with low actin affinity

Preclinical

N/A

[115]

Cytochalasin D

actin

Inhibit actin polymerization inhibits both the rate of actin polymerization and the interaction of actin filaments in solution

Preclinical

N/A

[116, 117]

IPA-3

Pak1

Impact on actin polymerization

Preclinical

N/A

[118, 119]

Bafilomycin A1

v-ATPase

Impact on lysosomal acidic pH

Preclinical

N/A

[120]

Hydroxychloroquine (HCQ)

Lysosomal

Inhibits lysosomal acidification

In the clinic, Phase 1 (completed)

Antiphospholipid Syndrome, Multiple Myeloma

[121]

GNS561

Lysosomal

Suppress lysosomal activity

Phase 1 (completed)

Primary and Secondary liver cancer

[122]