Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMW94E)

• DTT Name: FK506-binding protein 1A (FKBP1A)
• Synonyms: Rotamase; Peptidyl-prolyl cis-trans isomerase FKBP1A; PPIase FKBP1A; Immunophillin FKBP; Immunophilin FKBP12; FKBP12; FKBP1; FKBP-1A; FKBP-12; FK-binding protein 12; Calstabin-1; 12 kDa FKBP; 12 kDa FK506-binding protein
• Gene Name: FKBP1A
• DTT Type: Successful target; [1]
• BioChemical Class: Cis-trans-isomerase
• UniProt ID: FKB1A_HUMAN
• TTD ID: T76059
• EC Number: EC 5.2.1.8
• Sequence:
  MGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPFKFMLGKQEVIRGW
  EEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLE
• Function: Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand.
• Reactome Pathway:
  Calcineurin activates NFAT (R-HSA-2025928)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (R-HSA-2173791)
  TGFBR1 LBD Mutants in Cancer (R-HSA-3656535)
  Potential therapeutics for SARS (R-HSA-9679191)
  mTORC1-mediated signalling (R-HSA-166208)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GPI-1485	DM64ZYM	Parkinson disease	8A00.0	Phase 2	[2]
SDZ-281-240	DMPZ67G	Pruritus	EC90	Phase 2	[3]
AP1903	DM2LU8M	Transplant rejection	NE84	Phase 1/2	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gpi-1046	DMD5WK4	Parkinson disease	8A00.0	Terminated	[5]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-Hydroxy-2-Butanone	DM7BQ65	Discovery agent	N.A.	Investigative	[6]
FKB-001	DM9K834	Discovery agent	N.A.	Investigative	[6]
Heptyl-Beta-D-Glucopyranoside	DMPQBN0	Discovery agent	N.A.	Investigative	[7]
L-709,587	DM9KCYQ	Discovery agent	N.A.	Investigative	[6]
Methyl Methylsulfinylmethyl Sulfide	DMOCXLW	Discovery agent	N.A.	Investigative	[6]
MYRISTIC ACID	DMYX0BL	Discovery agent	N.A.	Investigative	[5]
Rapamycin Immunosuppressant Drug	DM678IB	Discovery agent	N.A.	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Parkinson's disease	8A00.0	Substantia nigra tissue	9.70E-01	-0.04	-0.09
Multiple myeloma	2C82	Bone marrow	2.70E-04	-0.62	-2.19
Sensitive skin	EA90	Skin	6.04E-01	0.27	0.75

References

• [1] Neural roles of immunophilins and their ligands. Mol Neurobiol. 1997 Oct;15(2):223-39.
• [2] Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42.
• [3] Clearing of psoriasis by a novel immunosuppressive macrolide. J Invest Dermatol. 1996 Apr;106(4):701-10.
• [4] Using gene transfer to circumvent off-target effects. Gene Ther. 2008 May;15(10):759-64.
• [5] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.