Table 1 Summary of common inhibitors targeting protein lipidation
Lipidation | Inhibitors | Mechanism | Latest developmental stage | Effects or applications | Ref. |
|---|---|---|---|---|---|
S-palmitoylation | 2-bromopalmitate | Irreversible pan-depalmitoylation agent | In vitro and in vivo study | Inhibit tumour cell proliferation and tumour growth | |
Metformin | Inhibition of fatty acid synthase-dependent palmitoylation | In vitro and in vivo study | Anti-inflammatory role in macrophages | ||
Artemisinin | Covalently binds and inhibits DHHC6 | In vitro study | / | ||
Prilocaine | Weaken DHHC15 transcripts | In vitro and in vivo study | Inhibit tumour cell proliferation, self-renewal and tumour growth | ||
Lidocaine | Weaken DHHC15 transcripts | In vitro and in vivo study | Inhibit tumour cell proliferation, self-renewal and tumour growth | ||
Procaine | Weaken DHHC15 transcripts | In vitro and in vivo study | Inhibit tumour cell proliferation, self-renewal and tumour growth | ||
Ropivacaine | Weaken DHHC15 transcripts | In vitro and in vivo study | Inhibit tumour cell proliferation, self-renewal and tumour growth | ||
Palmostatin B | Broad-spectrum inhibitor of APT1/2, PPT1, ABHD17A/B/C as well as other lipid-processing serine hydrolases | In vitro study | Suppress cell viability in N-Ras mutant melanoma cells | ||
Palmostatin M | Broad-spectrum inhibitor of APT1/2, PPT1, ABHD17A/B/C as well as other lipid-processing serine hydrolases | In vitro study | Inhibit Legionella and Mycobacterium species growth | ||
ML211 | Inhibition of APT1, APT2, ABHD11 and PPT1 | In vitro study | / | ||
H-151 | Occupy the palmitoylation site | In vitro and in vivo study | Reduce cytokine responses | ||
HCQ | Inhibition of PPT1 | In vivo study | Inhibit tumour growth of HCC in xenograft model | ||
ML348 | Inhibition of APT1 | In vitro and in vivo study | Reverse neuropathology, locomotor deficits, and anxio-depressive behaviours; deteriorate myocardial pyroptosis, infarct size and cardiac function in AML mice | ||
ML349 | Inhibition of APT2 | In vitro and in vivo study | Repress UVB-induced melanomagenesis | ||
ABD957 | Inhibition of ABHD17 | In vitro study | Inhibit N-Ras-mutant AML cell growth | ||
N-myristoylation | 2-hydroxymyristic acid | Inhibition of NMTs | In vitro study | Inhibit viral multiplication | |
D-NMAPPD (B13) | Inhibition of NMT1 | In vitro and in vivo study | Inhibit cell-cycle progression and growth of xenograft tumours | ||
LCL204 | Inhibition of NMT1 | In vitro study | / | ||
Tris-DBA palladium | Inhibition of NMT1 | In vitro and in vivo study | Inhibit melanoma cell proliferation and growth of tumours | ||
IMP-366 (DDD85646) | Inhibition of NMT1 and NMT2 | In vitro and in vivo study | Inhibit Trypanosoma cruzi | ||
IMP-1088 | Inhibition of NMT1 and NMT2 | In vitro study | Inhibit the replication of rhinovirus, poliovirus, foot-and-mouth disease virus, and vaccinia virus | ||
IMP-1002 | Inhibition of Plasmodium falciparum NMT | In vitro study | Disrupt Plasmodium falciparum development and growth | ||
IMP-105 | Inhibition of Leishmania NMT | In vitro study | Anti-Leishmanial activity | ||
RO-09-4879 | Inhibition of Candida albicans NMT | In vitro study | Antifungal activity against Candida albicans | ||
PCLX-001 | Inhibition of NMT1 and NMT2 | phase I clinical trial | Test in B-cell non-hodgkin lymphoma and advanced solid malignancies | ||
Asciminib | targeting the myristoyl pocket of the BCR-ABL1 tyrosine kinase | FDA approval | Treatment of adult patients with Ph+ CML-CP, previously treated with ≥ 2 TKIs, and Ph+ CML-CP with the T315I mutation | ||
S-prenylation | Statin | Inhibition of FPP and GGPP biosynthesis | Phase II clinical trial | Test in HGPS | / |
Bisphosphonates | Inhibition of the FPPS activity and the synthesis of FPP and GGPP | Phase II clinical trial | Test in Progeria | / | |
FPP analogues | Inhibition of FTase | In vitro study | / | ||
BMS-184467 | Inhibition of FTase | In vitro study | Inhibit the growth of ras transformed cells | ||
BMS-185878 | Inhibition of FTase | In vitro study | Inhibit the growth of ras transformed cells | ||
BMS-214662 | Inhibition of FTase | Phase I clinical trial | Test in solid cancer and haematologic disease | ||
tipifarnib | Inhibition of FTase | Phase III clinical trial | Test in solid cancer, haematologic disease | ||
lonafarnib | Inhibition of FTase | FDA approval | Treatment of HGPS and processing-deficient progeroid laminopathies | ||
GGTI-2418 | Inhibition of GGTase-I | Phase I clinical trial | Test in advanced malignancies | ||
S-prenylation | GGTI-2154 | Inhibition of GGTase-I | In vitro and in vivo study | Inhibit tumour growth of H-Ras transgenic mice | |
FGTI-2734 | Inhibition of FTase and GGTase-I | In vitro and in vivo study | Inhibit tumour cell proliferation and tumour growth; suppress mast cell-dependent anaphylaxis | ||
L-778,123 | Inhibition of FTase and GGTase-I | Phase I clinical trial | Test in advanced solid cancers | ||
NSC1011 | Inhibition of RCE1 | In vitro study | / | ||
UCM-1336 | Inhibition of ICMT | In vitro and in vivo study | Induce cell death in Ras-mutated tumour cell lines and inhibiting tumour growth | ||
Cysmethynil | Inhibition of ICMT | In vitro and in vivo study | Induce cell death in tumour cells and inhibiting tumour growth | ||
Compound 8.12 | Inhibition of ICMT | In vitro and in vivo study | Induce cell death in tumour cells and inhibiting tumour growth | ||
C75 | Inhibition of ICMT | In vitro and in vivo study | Delay ageing and promote the proliferation of HGPS Cells | ||
GPI anchor | SHAM | Inhibition of protozoan de-N-acetylase in the GPI pathway | In vitro study | Suppress P. falciparum 3D7 growth at trophozoite stages | |
BIQ | Inhibition of fungal Gwt1 in the GPI pathway | In vitro study | Reduce C. albicans cell adherence | ||
Gepinacin | Inhibition of fungal Gwt1 in the GPI pathway | In vitro study | Antifungal activity against C. albicans | ||
G365 | Inhibition of fungal Gwt1 in the GPI pathway | In vitro study | Antifungal potency against C. albicans | ||
G884 | Inhibition of fungal Gwt1 in the GPI pathway | In vitro study | Antifungal potency against C. albicans and others | ||
Compound A1 | Inhibition of fungal Gwt1 in the GPI pathway | In vitro and in vivo study | Antifungal potency against drug-resistant C. auris and C. albicans | ||
APX001 | Inhibition of fungal Gwt1 in the GPI pathway | Phase II clinical trial | Test in candidemia and other invasive fungal infections | ||
M743 | Inhibition of fungal MCD4 in the GPI pathway | In vitro study | Antifungal potency against C. albicans and others | ||
M720 | Inhibition of fungal MCD4 in the GPI pathway | In vitro study | Antifungal potency against C. albicans and others | ||
Cholesterylation | CID 5717 | Inhibition of the cholesterol-dependent autocleavage of Hh protein | In vitro study | / | |
CID 72303 | Inhibition of the cholesterol-dependent autocleavage of Hh protein | In vitro study | / |
