Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMSIMKZ)

• Drug Name: PD-83176 Drug Info
• Synonyms: CHEMBL217423; SCHEMBL8713501; BDBM50059876; PD-83176; Cbz-His-Tyr(OBn)-Ser(OBn)-Trp-DAla-NH2; [(S)-1-[(S)-1-{(S)-2-Benzyloxy-1-[(S)-1-((R)-1-carbamoyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethylcarbamoyl]-ethylcarbamoyl}-2-(4-benzyloxy-phenyl)-ethylcarbamoyl]-2-(3H-imidazol-4-yl)-ethyl]-carbamic acid benzyl ester; [(S)-1-[(S)-1-{(S)-2-Benzyloxy-1-[(S)-1-((R)-1-carbamoyl-ethylcarbamoyl)-2-(1H-indol-3-yl)-ethylcarbamoyl]-ethylcarbamoyl}-2-(4-benzyloxy-phenyl)-ethylcarbamoyl]-2-(1H-imidazol-4-yl)-ethyl]-carbamic acid be

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9919495
  TTD Drug ID: DMSIMKZ

Molecule-Related Drug Atlas

Drug(s) Targeting Farnesyl protein transferase (Ftase)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lonafarnib	DMGM2Z6	Hutchinson-Gilford progeria syndrome	LD2B	Approved	[2]
Zarnestra	DMF30HL	Acute myeloid leukaemia	2A60	Phase 3	[3]
L-778123	DMWSC5L	Lymphoma	2A80-2A86	Phase 1	[4]
GGTI-2418	DM8U23L	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
BMS214662	DM5M48F	Non-small-cell lung cancer	2C25.Y	Phase 1	[6]
L-745631	DM4UP7R	Solid tumour/cancer	2A00-2F9Z	Terminated	[7]
ABT-839	DM4UN9A	Non-small-cell lung cancer	2C25.Y	Terminated	[8]
MANUMYCIN A	DM1SWOY	N. A.	N. A.	Terminated	[9]
SCH-44342	DMUL4VX	N. A.	N. A.	Terminated	[10]
RPR-113829	DMJ63GW	N. A.	N. A.	Terminated	[11]

Drug(s) Targeting Geranylgeranyl transferase I (GGTase-I)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-778123	DMWSC5L	Lymphoma	2A80-2A86	Phase 1	[4]
L-745631	DM4UP7R	Solid tumour/cancer	2A00-2F9Z	Terminated	[7]
GGTI-298	DM1CG0J	N. A.	N. A.	Terminated	[12]
A-313326	DML4P6O	Discovery agent	N.A.	Investigative	[13]
J-109,390	DM9SFGB	Discovery agent	N.A.	Investigative	[14]
L-269,289	DMV6018	Discovery agent	N.A.	Investigative	[14]

Drug(s) Targeting CAAX farnesyltransferase beta (FNTB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-745631	DM4UP7R	Solid tumour/cancer	2A00-2F9Z	Terminated	[7]
ABT-839	DM4UN9A	Non-small-cell lung cancer	2C25.Y	Terminated	[13]
MANUMYCIN A	DM1SWOY	N. A.	N. A.	Terminated	[9]
SCH-44342	DMUL4VX	N. A.	N. A.	Terminated	[7]
RPR-113829	DMJ63GW	N. A.	N. A.	Terminated	[11]
RPR-114334	DMAIJT6	N. A.	N. A.	Terminated	[11]
L-731735	DM1XBKC	Solid tumour/cancer	2A00-2F9Z	Terminated	[7]
FUSIDIENOL	DMI1Y92	N. A.	N. A.	Terminated	[15]
ABT-100	DMPFLS5	Solid tumour/cancer	2A00-2F9Z	Terminated	[16]
B-956	DM1IO9X	Solid tumour/cancer	2A00-2F9Z	Terminated	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CAAX farnesyltransferase beta (FNTB)	TT7WZIJ	FNTB_HUMAN	Inhibitor	[1]
Farnesyl protein transferase (Ftase)	TTXQKM3	FNTA_HUMAN; FNTB_HUMAN	Inhibitor	[1]
Geranylgeranyl transferase I (GGTase-I)	TTX20QP	PGTB1_HUMAN	Inhibitor	[1]

References

• [1] Structure-activity relationships of cysteine-lacking pentapeptide derivatives that inhibit ras farnesyltransferase. J Med Chem. 1997 Jan 17;40(2):192-200.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [3] Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics. 2008 Sep;2(3):491-500.
• [4] 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.
• [5] Company report (Prescient)
• [6] Farnesyltransferase inhibitor BMS-214662 induces apoptosis in B-cell chronic lymphocytic leukemia cells. Leukemia. 2004 Oct;18(10):1599-604.
• [7] Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90.
• [8] Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1359-62.
• [9] A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.
• [10] Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. J Med Chem. 1999 Jun 17;42(12):2125-35.
• [11] Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. J Med Chem. 1997 Jun 6;40(12):1763-7.
• [12] 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.
• [13] 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.
• [14] Geranylgeranyltransferase I of Candida albicans: null mutants or enzyme inhibitors produce unexpected phenotypes. J Bacteriol. 2000 Feb;182(3):704-13.
• [15] Modeling of binding modes and inhibition mechanism of some natural ligands of farnesyl transferase using molecular docking. J Med Chem. 2002 Mar 28;45(7):1460-5.
• [16] Potent farnesyltransferase inhibitor ABT-100 abrogates acute allograft rejection. J Heart Lung Transplant. 2005 Sep;24(9):1403-9.
• [17] Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res. 1995 Nov 15;55(22):5310-4.