Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE3RAC)

DTT Name	Dickkopf-related protein 1 (DKK1)
Synonyms	hDkk1; hDkk-1; UNQ492/PRO1008; Dkk1; Dkk-1; Dickkopfrelated protein 1; Dickkopf1; Dickkopf-1
Gene Name	DKK1
DTT Type	Clinical trial target	[1]
BioChemical Class	Dickkopf protein
UniProt ID	DKK1_HUMAN
TTD ID	T56697
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Sequence	MMALGAAGATRVFVAMVAAALGGHPLLGVSATLNSVLNSNAIKNLPPPLGGAAGHPGSAV SAAPGILYPGGNKYQTIDNYQPYPCAEDEECGTDEYCASPTRGGDAGVQICLACRKRRKR CMRHAMCCPGNYCKNGICVSSDQNHFRGEIEETITESFGNDHSTLDGYSRRTTLSSKMYH TKGQEGSVCLRSSDCASGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCG EGLSCRIQKDHHQASNSSRLHTCQRH
Function	DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease. Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti-apoptotic activity. Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6.
KEGG Pathway	Wnt signaling pathway (hsa04310 )
Reactome Pathway	Negative regulation of TCF-dependent signaling by WNT ligand antagonists (R-HSA-3772470 ) TCF dependent signaling in response to WNT (R-HSA-201681 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BHQ880	DMSROM4	Multiple myeloma	2A83	Phase 2	[2]
DKN-01	DMOHT5V	Biliary tract cancer	2C17	Phase 2	[3]
PF-04840082	DMDSCQG	Osteoporosis	FB83.0	Phase 1	[4]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Osteoporosis	FA20	Bone marrow	2.29E-01	-0.8	-0.66
Multiple myeloma	2C82	Bone marrow	5.31E-07	2.97	5.21
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References

1	Biological therapy for osteoporosis. Clin Calcium. 2014 Jun;24(6):919-25.
2	Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood. 2009 Jul 9;114(2):371-9.
3	The anti-DKK1 antibody DKN-01 as an immunomodulatory combination partner for the treatment of cancer. Expert Opin Investig Drugs. 2020 Jul;29(7):639-644.
4	The application of target information and preclinical pharmacokinetic/pharmacodynamic modeling in predicting clinical doses of a Dickkopf-1 antibody for osteoporosis. J Pharmacol Exp Ther. 2010 Apr;333(1):2-13.