Molecule Information

General Information of the Molecule (ID: Mol01949)

• Name: C-C motif chemokine receptor 5 (CCR5) ,Mus musculus
• Synonyms: Ccr5; Cmkbr5
• Molecule Type: Protein
• Gene Name: CCR5
• Gene ID: 12774
• Location: chr9:123,921,580-123,947,736[+]
• Sequence:
  MDFQGSVPTYSYDIDYGMSAPCQKINVKQIAAQLLPPLYSLVFIFGFVGNMMVFLILISC
  KKLKSVTDIYLLNLAISDLLFLLTLPFWAHYAANEWVFGNIMCKVFTGLYHIGYFGGIFF
  IILLTIDRYLAIVHAVFALKVRTVNFGVITSVVTWAVAVFASLPEIIFTRSQKEGFHYTC
  SPHFPHTQYHFWKSFQTLKMVILSLILPLLVMVICYSGILHTLFRCRNEKKRHRAVRLIF
  AIMIVYFLFWTPYNIVLLLTTFQEFFGLNNCSSSNRLDQAMQATETLGMTHCCLNPVIYA
  FVGEKFRSYLSVFFRKHMVKRFCKRCSIFQQDNPDRASSVYTRSTGEHEVSTGL
• Function: Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor.
• Uniprot ID: CCR5_MOUSE
• Ensembl ID: ENSMUSG00000079227
• HGNC ID: HGNC:1606

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: 9989
Family: Muridae
Genus: Mus
Species: Mus musculus

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Maraviroc

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Glioblastoma [1]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Sensitive Drug: Maraviroc
• Molecule Alteration: Function; Inhibition
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: CCL5-CCR5 signaling pathway; Inhibition; has05163
• In Vivo Model: Intracranial GBM patient-derived xenograft model; Mus musculus
• Experiment for Molecule Alteration: Neutral comet assay; ELISA assay; Immunofluorescence staining analysis; Immunohistochemistry staining analysi; Immunoblot assay
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The authors uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ.

References

• Ref 1: Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling .Cell Res. 2021 Oct;31(10):1072-1087. doi: 10.1038/s41422-021-00528-3. Epub 2021 Jul 8. 10.1038/s41422-021-00528-3