Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Polo-like kinase 4 (PLK4)
• Synonyms: Serine/threonine-protein kinase Sak; Serine/threonine-protein kinase PLK4; Serine/threonine-protein kinase 18; STK18; SAK; PLK-4
• Gene Name: PLK4
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: PLK4_HUMAN
• TTD ID: T71374
• EC Number: EC 2.7.11.21
• Sequence:
  MATCIGEKIEDFKVGNLLGKGSFAGVYRAESIHTGLEVAIKMIDKKAMYKAGMVQRVQNE
  VKIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNGEMNRYLKNRVKPFSENEARHFMHQI
  ITGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLKMPHEKHYTLCGTPNYISP
  EIATRSAHGLESDVWSLGCMFYTLLIGRPPFDTDTVKNTLNKVVLADYEMPSFLSIEAKD
  LIHQLLRRNPADRLSLSSVLDHPFMSRNSSTKSKDLGTVEDSIDSGHATISTAITASSST
  SISGSLFDKRRLLIGQPLPNKMTVFPKNKSSTDFSSSGDGNSFYTQWGNQETSNSGRGRV
  IQDAEERPHSRYLRRAYSSDRSGTSNSQSQAKTYTMERCHSAEMLSVSKRSGGGENEERY
  SPTDNNANIFNFFKEKTSSSSGSFERPDNNQALSNHLCPGKTPFPFADPTPQTETVQQWF
  GNLQINAHLRKTTEYDSISPNRDFQGHPDLQKDTSKNAWTDTKVKKNSDASDNAHSVKQQ
  NTMKYMTALHSKPEIIQQECVFGSDPLSEQSKTRGMEPPWGYQNRTLRSITSPLVAHRLK
  PIRQKTKKAVVSILDSEEVCVELVKEYASQEYVKEVLQISSDGNTITIYYPNGGRGFPLA
  DRPPSPTDNISRYSFDNLPEKYWRKYQYASRFVQLVRSKSPKITYFTRYAKCILMENSPG
  ADFEVWFYDGVKIHKTEDFIQVIEKTGKSYTLKSESEVNSLKEEIKMYMDHANEGHRICL
  ALESIISEEERKTRSAPFFPIIIGRKPGSTSSPKALSPPPSVDSNYPTRERASFNRMVMH
  SAASPTQAPILNPSMVTNEGLGLTTTASGTDISSNSLKDCLPKSAQLLKSVFVKNVGWAT
  QLTSGAVWVQFNDGSQLVVQAGVSSISYTSPNGQTTRYGENEKLPDYIKQKLQCLSSILL
  MFSNPTPNFH
• Function: Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification. Serine/threonine-protein kinase that plays a central role in centriole duplication.
• KEGG Pathway: FoxO signaling pathway (hsa04068)
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CFI-400945	DM3BN4W	Breast cancer	2C60-2C65	Phase 2	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XMD8-92	DMZIHKY	Discovery agent	N.A.	Investigative	[1]

References

• [1] Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 2010 Sep 14;18(3):258-67.
• [2] Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell. 2014 Aug 11;26(2):163-76.