Table 1.

Representative cell-permeable MPs reported since 2017. CPP motifs are highlighted in green color.

Compd No.	Compound structure	Target (KD or IC50 value for target)	Biological activity	Cell entry mechanism	Refs
1		NNMT(IC50 = 1.9 nM for human NNMT)	In vitro (IC50 = 0.77 μM for NNMT inhibition in HEK293 cells)	Passive diffusion	[25]
2		β-catenin (IC50 = 5.4 μM)	In vitro; in vivo (rescued eye development in zebrafish model)	Passive diffusion	[26]
3		MDM2 (KD = 26 nM)	In vitro by stapled analog (activated p53 in U2OS cells at 30 μM)	Potentially passive diffusion	[28]
4		TEAD (KD = 0.7 pM for human TEAD)	In vitro (activated Hippo-associated genes in cardiomyocytes at 30 μM)	Endocytosis	[33]
5		RbAp48 (KD = 8.6 nM)	In vitro (increased p53 level in U2OS cells)	Endocytosis	[34]
6		Tankyrase (KD = 440 nM)	In vitro (decreased Wnt reporter activity in HEK293T cells [IC50 ≈ 50 μM])	Endocytosis	[36]
7		Jun subunit of transcription factor activator protein-1 (KD =2 μM)	In vitro (antiproliferative activity against MCF-7 and ZR75-1 breast cancer cells)	Endocytosis	[37]
8		HDAC (IC50 = 99-303 nM for different HDAC isoforms)	In vitro; in vivo (TGI @ 50 mg/kg in PA-1 and NTERA-2 mouse xenograft models)	Endocytosis	[38]
9		Calcineurin (KD = 16 nM)	In vitro; in vivo (prevented acute lung injury @ 3-5 mg/kg in a mouse model)	Endocytosis	[41]
10		Keapl (IC50 = 153 nM)	In vitro (inhibited Keap1/Nrf2 PPI in ARE reporter-HepG2 cell line [EC50 ≈ 1.1 μM])	Endocytosis	[43]
11		Pin1 (IC50 = 220 nM)	In vitro (inhibited the proliferation of HeLa cervical cancer cells)	Endocytosis	[46]
12		Grb2 SH2 domain (IC50 = 400 nM)	In vitro (inhibited Grb2/Ras signaling in MDA-MB-468 breast cancer cells [IC50 ≈ 15 MM])	Endocytosis	[47]
13		NEMO(IC50 = 1.0 μM)	In vitro (inhibition of TNFα-induced NF-κB activation [IC50 = 10 μM])	Endocytosis	[49]
14		K-, H-, and N-Ras (KD = 21 nM for KRasG12V-GppNHp)	In vitro; in vivo (TGI @ 1-5 mg/kg in A549 and H358 mouse xenograft models)	Endocytosis	[50]
15		PDZ domain of CFTR-associated ligand (KD = 6 nM)	In vitro; ex vivo (improved ion channel activity of F508del-CFTR by 3-fold [EC50 ≈ 10 nM])	Endocytosis	[51]
16		Ras (KD = 2 μM for HRas)	In vitro (antiproliferative activity in Ras mutant cancer cells)	Endocytosis	[53]
17		Bcl2A1 (apparent Ki <0.1 nM)	In vitro (covalent modification of Bcl2A1 in U937 lymphoma cells)	Unknown	[68]
18		β-catenin (KD = 123 nM)	In vitro (antiproliferative effect in Wnt-addicted colorectal cancer cells DLD-1 and SW480)	Unknown	[69]
19		MDM2/X (KD = 0.87 and 3.9 nM for MDM2 and MDMX)	In vitro (antiproliferative effect in HCT116 cells [IC50 ≈ 25 μM])	Unknown	[71]
20		β-catenin (KD = 91 nM)	In vitro (inhibition of Wnt signaling in HEK293T reporter cell line [IC50 = 8 μM])	Unknown	[74]
21		Keap1 (KD = 35 nM)	In vitro (increased the expression of Nrf2-regulated genes in HEK293T cells)	Unknown (potentially endocytosis)	[79]
22		UEV domain of TSG101 protein (KD = 11.9 μM)	In vitro (viruslike particle budding assay in HEK293T cells [IC50 ≈ 2 μM])	Unknown	[83]
23		KRasG12D (EC50 = 22 nM)	In vitro; in vivo (TGI @40 mg/kg in PANC-1 mouse xenograft model)	Unknown	[84]
24		K48Ub tetramer (KD = 9 nM)	In vitro; in vivo (TGI @1 mg/kg in mouse model)	Unknown	[85]
25		LC (KD = 120 and 192 nM for LC3A and LC3B, respectively)	In vitro (inhibited autophagy in HeLa cervical cancer cells)	Unknown	[87]
26		MyD88	In vivo (reduced disease severity @ 10 mg/kg in sclerosis mouse models)	Unknown	[88]