Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTX20QP)

• DTT Name: Geranylgeranyl transferase I (GGTase-I)
• Synonyms: Type I protein geranyl-geranyltransferase subunit beta; Type I protein geranyl-geranyltransferase beta subunit of Saccharomyces cerevisiae; RAS proteins geranylgeranyltransferase beta subunit; PGGT; Geranylgeranyl transferase type-1 subunit beta; Geranylgeranyl transferase type I subunit beta; GGTase-I-beta of Saccharomyces cerevisiae; GGTase-I-beta; CDC43
• Gene Name: PGGT1B
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Alkyl aryl transferase
• UniProt ID: PGTB1_HUMAN
• TTD ID: T76396
• EC Number: EC 2.5.1.59
• Sequence:
  MAATEDERLAGSGEGERLDFLRDRHVRFFQRCLQVLPERYSSLETSRLTIAFFALSGLDM
  LDSLDVVNKDDIIEWIYSLQVLPTEDRSNLNRCGFRGSSYLGIPFNPSKAPGTAHPYDSG
  HIAMTYTGLSCLVILGDDLSRVNKEACLAGLRALQLEDGSFCAVPEGSENDMRFVYCASC
  ICYMLNNWSGMDMKKAITYIRRSMSYDNGLAQGAGLESHGGSTFCGIASLCLMGKLEEVF
  SEKELNRIKRWCIMRQQNGYHGRPNKPVDTCYSFWVGATLKLLKIFQYTNFEKNRNYILS
  TQDRLVGGFAKWPDSHPDALHAYFGICGLSLMEESGICKVHPALNVSTRTSERLLDLHQS
  WKTKDSKQCSENVHIST
• Function: Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B.

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-778123	DMWSC5L	Lymphoma	2A80-2A86	Phase 1	[1]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GGTI-298	DM1CG0J	N. A.	N. A.	Terminated	[2]
L-745631	DM4UP7R	Solid tumour/cancer	2A00-2F9Z	Terminated	[3]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-313326	DML4P6O	Discovery agent	N.A.	Investigative	[4]
J-109,390	DM9SFGB	Discovery agent	N.A.	Investigative	[5]
L-269,289	DMV6018	Discovery agent	N.A.	Investigative	[5]
PD-83176	DMSIMKZ	Discovery agent	N.A.	Investigative	[6]

References

• [1] Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein trans... Mol Cancer Ther. 2002 Jul;1(9):747-58.
• [2] The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21(WAF1/CIP1/SDI1) in a p53-independent manner. J Biol Chem. 1997 Oct 24;272(43):27224-9.
• [3] Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90.
• [4] Design and synthesis of o-trifluoromethylbiphenyl substituted 2-amino-nicotinonitriles as inhibitors of farnesyltransferase. Bioorg Med Chem Lett. 2005 Jan 3;15(1):153-8.
• [5] Geranylgeranyltransferase I of Candida albicans: null mutants or enzyme inhibitors produce unexpected phenotypes. J Bacteriol. 2000 Feb;182(3):704-13.
• [6] Structure-activity relationships of cysteine-lacking pentapeptide derivatives that inhibit ras farnesyltransferase. J Med Chem. 1997 Jan 17;40(2):192-200.