Target Information

Target General Information

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Target ID

T13127

Target Name

Farnesyl protein transferase (Ftase)

Synonyms

Ras proteins prenyltransferase; Protein farnesyltransferase; Ftase; CAAX farnesyltransferase

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Gene Name

FNTB; FNTA

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Premature ageing appearance [ICD-11: LD2B]

Function

Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1prenylation and activation.

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BioChemical Class

Alkyl aryl transferase

UniProt ID

FNTA_HUMAN ; FNTB_HUMAN

Sequence

MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDS
PSYVLYRDRAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSERAFKLT
RDAIELNAANYTVWHFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLR
DPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQR
YFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNLLNQLL
DLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEYWRYIG
RSLQSKHSTENDSPTNVQQ

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Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Lonafarnib

Drug Info

Approved

Hutchinson-Gilford progeria syndrome

[2]

Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

Zarnestra

Drug Info

Phase 3

Acute myeloid leukaemia

[3]

BMS214662

Drug Info

Phase 1

Non-small-cell lung cancer

[4], [5], [6]

GGTI-2418

Drug Info

Phase 1

Solid tumour/cancer

[7]

L-778123

Drug Info

Phase 1

Lymphoma

[8], [9]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

ABT-839

Drug Info

Terminated

Non-small-cell lung cancer

[10]

AZD3409

Drug Info

Terminated

Solid tumour/cancer

[11], [12]

L-731735

Drug Info

Terminated

Solid tumour/cancer

[13]

L-745631

Drug Info

Terminated

Solid tumour/cancer

[14]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 5 Modulator drugs

Lonafarnib

Drug Info

[2]

Zarnestra

Drug Info

[1]

BMS214662

Drug Info

[15]

GGTI-2418

Drug Info

[16]

L-778123

Drug Info

[17]

Inhibitor

[+] 19 Inhibitor drugs

ABT-839

Drug Info

[18]

AZD3409

Drug Info

[19], [20], [21]

L-731735

Drug Info

[22]

L-745631

Drug Info

[23]

MANUMYCIN A

Drug Info

[24]

RPR-113829

Drug Info

[25]

RPR-114334

Drug Info

[25]

SCH-44342

Drug Info

[26]

(Z)-2-Methyl-3-tetradecyl-but-2-enedioic acid

Drug Info

[23]

ACTINOPLANIC ACID A

Drug Info

[23]

ALPHA-HYDROXYFARNESYLPHOSPHONIC ACID

Drug Info

[27]

BMS-404683

Drug Info

[28]

CLAVARINONE

Drug Info

[29]

FARNESYL

Drug Info

[27]

GERANYLGERANYL DIPHOSPHATE

Drug Info

[27]

PB-27

Drug Info

[28]

PB-80

Drug Info

[28]

PB-81

Drug Info

[28]

PD-83176

Drug Info

[30]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics. 2008 Sep;2(3):491-500.

REF 2

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020

REF 3

ClinicalTrials.gov (NCT00093990) Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML). U.S. National Institutes of Health.

REF 4

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8026).

REF 5

ClinicalTrials.gov (NCT00006242) BMS-214662 in Treating Patients With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT00022529) BMS-214662 Plus Trastuzumab in Treating Patients With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 7

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030147)

REF 8

ClinicalTrials.gov (NCT00003430) L-778,123 in Treating Patients With Recurrent or Refractory Solid Tumors. U.S. National Institutes of Health.

REF 9

A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer. Clin Cancer Res. 2004 Aug 15;10(16):5447-54.

REF 10

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014561)

REF 11

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015097)

REF 13

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002714)

REF 14

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007537)

REF 15

Farnesyltransferase inhibitor BMS-214662 induces apoptosis in B-cell chronic lymphocytic leukemia cells. Leukemia. 2004 Oct;18(10):1599-604.

REF 16

Company report (Prescient)

REF 17

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.

REF 18

Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1359-62.

REF 19

AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to the EGFR tyrosine kinase inhibitor gefitinib. Breast Cancer Res Treat. 2007 May;102(3):275-82.

REF 20

Radiosensitizing effects of the prenyltransferase inhibitor AZD3409 against RAS mutated cell lines. Cancer Biol Ther. 2006 Sep;5(9):1206-10.

REF 21

Quantification of farnesylmethylcysteine in lysates of peripheral blood mononuclear cells using liquid chromatography coupled with electrospray tandem mass spectrometry: pharmacodynamic assay for farnesyl transferase inhibitors. Anal Chem. 2006 Apr 15;78(8):2617-22.

REF 22

N-Arylalkyl pseudopeptide inhibitors of farnesyltransferase. J Med Chem. 1998 Jul 2;41(14):2651-6.

REF 23

Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90.

REF 24

A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.

REF 25

Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. J Med Chem. 1997 Jun 6;40(12):1763-7.

REF 26

Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. J Med Chem. 1999 Jun 17;42(12):2125-35.

REF 27

The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

REF 28

Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. J Med Chem. 2005 Jun 2;48(11):3704-13.

REF 29

Clavaric acid and steroidal analogues as Ras- and FPP-directed inhibitors of human farnesyl-protein transferase. J Med Chem. 1998 Nov 5;41(23):4492-501.

REF 30

Structure-activity relationships of cysteine-lacking pentapeptide derivatives that inhibit ras farnesyltransferase. J Med Chem. 1997 Jan 17;40(2):192-200.

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