GGTase I

GGTase I catalyzes CaaX protein geranylgeranylation, a lipid posttranslational modification required by many proteins controlling growth, differentiation, morphology, cytoskeletal organization, and vesicle trafficking^[1]. Mechanistically, it modifies substrates including Rho, Rac, Cdc42, Rap1, and G-protein γ subunits, thereby supporting membrane association and small-GTPase signaling^[2]^[3]. In cancer-relevant models, GGTase I inhibitors disrupted oncogenic survival pathways, inhibited anchorage-dependent and anchorage-independent growth, and induced apoptosis through functionally distinct effects on RalA and RalB^[4]. In human pancreatic carcinoma cells, GGTI-298 induced p21^WAF1/CIP1^ transcription through Sp1-related promoter activity and by preventing RhoA from repressing p21 induction^[5]. Compared with FTase and RabGGTase, GGTase I belongs to the CaaX prenyltransferases, whereas Rab GTPases require REP and Rab geranylgeranyl transferase machinery^[1]^[6]. For experimental applications, GGTI-298, GGTI-2417, and GGTI-2147 serve as tools to test geranylgeranylation-dependent localization, signaling, growth, apoptosis, and prenylation defects^[4]^[5]^[7].

References:

[1]. Lane KT, et al. Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res. 2006 Apr;47(4):681-99. [Content Brief]

[2]. Peterson YK, et al. Discovery of geranylgeranyltransferase-I inhibitors with novel scaffolds by the means of quantitative structure-activity relationship modeling, virtual screening, and experimental validation. J Med Chem. 2009 Jul 23;52(14):4210-20. [Content Brief]

[3]. Berndt N, et al. Measurement of protein farnesylation and geranylgeranylation in vitro, in cultured cells and in biopsies, and the effects of prenyl transferase inhibitors. Nat Protoc. 2011 Oct 27;6(11):1775-91. [Content Brief]

[4]. Falsetti SC, et al. Geranylgeranyltransferase I inhibitors target RalB to inhibit anchorage-dependent growth and induce apoptosis and RalA to inhibit anchorage-independent growth. Mol Cell Biol. 2007 Nov;27(22):8003-14. [Content Brief]

[5]. Adnane J, et al. p21(WAF1/CIP1) is upregulated by the geranylgeranyltransferase I inhibitor GGTI-298 through a transforming growth factor beta- and Sp1-responsive element: involvement of the small GTPase rhoA. Mol Cell Biol. 1998 Dec;18(12):6962-70. [Content Brief]

[6]. Leung KF, et al. Thematic review series: lipid posttranslational modifications. geranylgeranylation of Rab GTPases. J Lipid Res. 2006 Mar;47(3):467-75. [Content Brief]

[7]. Veluthakal R, et al. Metabolic Stress Induces Caspase-3 Mediated Degradation and Inactivation of Farnesyl and Geranylgeranyl Transferase Activities in Pancreatic β-Cells. Cell Physiol Biochem. 2016;39(6):2110-2120. [Content Brief]

GGTase I Inhibitors (2)

GGTase I 관련 제품 (2):

Cat. No.	상품명	효과	Purity

HY-161573

BAY-593	Inhibitor	99.94%
BAY-593 is an orally active GGTase-I inhibitor. BAY-593 can block YAP1/TAZ signaling in animals and has antitumor activity.

HY-161573A

(7S)-BAY-593	Inhibitor	99.61%
(7S)-BAY-593 is the S-enantiomer of BAY-593 (HY-161573). BAY-593 is an orally active GGTase-I inhibitor. BAY-593 can block YAP1/TAZ signaling in animals and has antitumor activity.

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