Last update 01 Nov 2024

FDPS x GGPS1

Last update 01 Nov 2024

Basic Info

Related Targets

FDPSGGPS1

Drugs associated with FDPS x GGPS1

AIM-1290

Target

FDPS x GGPS1

Mechanism

FDPS inhibitors [+1]

Active Org.

Takeda Pharmaceutical Co., Ltd. [+1]

Originator Org.

Stanford University

Active Indication

Malaria, Falciparum

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with FDPS x GGPS1

100 Translational Medicine associated with FDPS x GGPS1

0 Patents (Medical) associated with FDPS x GGPS1

Literatures (Medical) associated with FDPS x GGPS1

01 May 2024·Plant Physiology and Biochemistry

Isoprenyl diphosphate synthases of terpenoid biosynthesis in rose-scented geranium (Pelargonium graveolens)

Article

Author: Shasany, Ajit Kumar ; Kiran, N R ; Patel, Devendra Kumar ; Nagegowda, Dinesh A ; Mohapatra, Soumyajit ; Kumar, Ajay ; Jaiswal, Priyanka ; Patekar, Soumitra

The essential oil of Pelargonium graveolens (rose-scented geranium), an important aromatic plant, comprising mainly mono- and sesqui-terpenes, has applications in food and cosmetic industries. This study reports the characterization of isoprenyl disphosphate synthases (IDSs) involved in P. graveolens terpene biosynthesis. The six identified PgIDSs belonged to different classes of IDSs, comprising homomeric geranyl diphosphate synthases (GPPSs; PgGPPS1 and PgGPPS2), the large subunit of heteromeric GPPS or geranylgeranyl diphosphate synthases (GGPPSs; PgGGPPS), the small subunit of heteromeric GPPS (PgGPPS.SSUI and PgGPPS.SSUII), and farnesyl diphosphate synthases (FPPS; PgFPPS).All IDSs exhibited maximal expression in glandular trichomes (GTs), the site of aroma formation, and their expression except PgGPPS.SSUII was induced upon treatment with MeJA. Functional characterization of recombinant proteins revealed that PgGPPS1, PgGGPPS and PgFPPS were active enzymes producing GPP, GGPP/GPP, and FPP respectively, whereas both PgGPPS.SSUs and PgGPPS2 were inactive. Co-expression of PgGGPPS (that exhibited bifunctional G(G)PPS activity) with PgGPPS.SSUs in bacterial expression system showed lack of interaction between the two proteins, however, PgGGPPS interacted with a phylogenetically distant Antirrhinum majus GPPS.SSU. Further, transient expression of AmGPPS.SSU in P. graveolens leaf led to a significant increase in monoterpene levels. These findings provide insight into the types of IDSs and their role in providing precursors for different terpenoid components of P. graveolens essential oil.

21 Dec 2022·Microbiology Spectrum

Proteomic Analysis of a Hypervirulent Mutant of the Insect-Pathogenic Fungus Metarhizium anisopliae Reveals Changes in Pathogenicity and Terpenoid Pathways

Article

Author: Huang, Zhen ; Li, Chengzhou ; Huang, Wenyou ; Qi, Ping ; Keyhani, Nemat O. ; Huang, Shuaishuai ; Huang, Song ; Huang, Peiquan ; Yü, Dan

The mechanisms that underlie and contribute to microbial (fungal) virulence are known to be varied; however, the identification of contributing pathways beyond known virulence factors remains difficult. Using TMT-based proteomic analyses, changes in the proteomes of an M. anisopliae hypervirulent mutant and its wild-type parent were determined.

02 Dec 2021·OncogeneQ1 · MEDICINE

CRISPR screens identify cholesterol biosynthesis as a therapeutic target on stemness and drug resistance of colon cancer

Q1 · MEDICINE

Article

Author: Wang, Shiyan ; Liu, Weixin ; Chen, Huarong ; Sung, Joseph J Y ; Yang, Zhenjie ; Go, Minnie Y Y ; Soares, Fraser ; Yu, Jun ; Ahmed, Musaddeque ; Wong, Chi Chun ; He, Housheng Hansen ; Gao, Shanshan ; Zeng, Yong ; O'Brien, Catherine Adell

AbstractCancer stem cells (CSCs) are responsible for tumor progression, recurrence, and drug resistance. To identify genetic vulnerabilities of colon cancer, we performed targeted CRISPR dropout screens comprising 657 Drugbank targets and 317 epigenetic regulators on two patient-derived colon CSC-enriched spheroids. Next-generation sequencing of pooled genomic DNAs isolated from surviving cells yielded therapeutic candidates. We unraveled 44 essential genes for colon CSC-enriched spheroids propagation, including key cholesterol biosynthetic genes (HMGCR, FDPS, and GGPS1). Cholesterol biosynthesis was induced in colon cancer tissues, especially CSC-enriched spheroids. The genetic and pharmacological inhibition of HMGCR/FDPS impaired self-renewal capacity and tumorigenic potential of the spheroid models in vitro and in vivo. Mechanistically, HMGCR or FDPS depletion impaired cancer stemness characteristics by activating TGF-β signaling, which in turn downregulated expression of inhibitors of differentiation (ID) proteins, key regulators of cancer stemness. Cholesterol and geranylgeranyl diphosphate (GGPP) rescued the growth inhibitory and signaling effect of HMGCR/FDPS blockade, implying a direct role of these metabolites in modulating stemness. Finally, cholesterol biosynthesis inhibitors and 5-FU demonstrated antitumor synergy in colon CSC-enriched spheroids, tumor organoids, and xenografts. Taken together, our study unravels novel genetic vulnerabilities of colon CSC-enriched spheroids and suggests cholesterol biosynthesis as a potential target in conjunction with traditional chemotherapy for colon cancer treatment.

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