Target General Infomation
Target ID
T56697
Former ID
TTDNC00370
Target Name
DKK1 protein
Gene Name
DKK1
Synonyms
Dickkopf1; Dickkopfrelated protein 1; Dkk1; SK; hDkk1; DKK1
Target Type
Clinical Trial
Disease Multiple myeloma [ICD9: 203; ICD10: C90]
Osteoporosis [ICD9: 733.0, V07.4; ICD10: M80-M81, Z79.890]
Function
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. 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.
BioChemical Class
Dickkopf family
UniProt ID
Sequence
MMALGAAGATRVFVAMVAAALGGHPLLGVSATLNSVLNSNAIKNLPPPLGGAAGHPGSAV
SAAPGILYPGGNKYQTIDNYQPYPCAEDEECGTDEYCASPTRGGDAGVQICLACRKRRKR
CMRHAMCCPGNYCKNGICVSSDQNHFRGEIEETITESFGNDHSTLDGYSRRTTLSSKMYH
TKGQEGSVCLRSSDCASGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCG
EGLSCRIQKDHHQASNSSRLHTCQRH
Drugs and Mode of Action
Drug(s) BHQ-880 Drug Info Phase 2 Multiple myeloma [523373]
PF-04840082 Drug Info Phase 1 Osteoporosis [523352]
Modulator PF-04840082 Drug Info [530645]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Wnt signaling pathway
NetPath Pathway TGF_beta_Receptor Signaling Pathway
Wnt Signaling Pathway
FSH Signaling Pathway
Pathway Interaction Database Presenilin action in Notch and Wnt signaling
Wnt signaling network
Direct p53 effectors
Regulation of nuclear beta catenin signaling and target gene transcription
Validated targets of C-MYC transcriptional repression
Reactome TCF dependent signaling in response to WNT
Negative regulation of TCF-dependent signaling by WNT ligand antagonists
WikiPathways Mesodermal Commitment Pathway
Endoderm Differentiation
Differentiation Pathway
Cytodifferentiation (Part 3 of 3)
Primary Focal Segmental Glomerulosclerosis FSGS
Cardiac Progenitor Differentiation
References
Ref 523352ClinicalTrials.gov (NCT01293487) Safety And Tolerability Study Of RN564 In Women With Osteopenia And Healthy Men.. U.S. National Institutes of Health.
Ref 523373ClinicalTrials.gov (NCT01302886) Study of BHQ880 in Patients With High Risk Smoldering Multiple Myeloma. U.S. National Institutes of Health.
Ref 530645The 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.
Ref 532792Biological therapy for osteoporosis. Clin Calcium. 2014 Jun;24(6):919-25.

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