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Function Modulators

Crt0063465 View larger

CRT0063465

AOB13255

CAS N/A

Chemical Name: 3-(2-(4-Bromophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)propanoic acid

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QuantitymgUnit Price ($/mg or $/Unit)Final Price
15 $17.85 Total: $89.25
110 $15.12 Total: $151.20
125 $12.81 Total: $320.25
150 $10.92 Total: $546.00
1100 $9.45 Total: $945.00

Data sheet

Molecular FormulaC17H16BrN3O2
Molecular Weight374.24
SynonymCRT0063465; CRT-0063465; CRT 0063465
IUPAC/Chemical Name3-(2-(4-Bromophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-6-yl)propanoic acid
InChl KeySJELVUFWTXHLTJ-UHFFFAOYSA-N
InChl Code InChI=1S/C17H16BrN3O2/c1-10-14(7-8-17(22)23)11(2)21-16(19-10)9-15(20-21)12-3-5-13(18)6-4-12/h3-6,9H,7-8H2,1-2H3,(H,22,23)
SMILES CodeO=C(O)CCC1=C(C)N2C(N=C1C)=CC(C3=CC=C(Br)C=C3)=N2

More info

Novel Ligand of Human PGK1 and Stress Sensor DJ1, Modulating the Shelterin Complex and Telomere Length Regulation

What is CRT0063465?

  • CRT0063465 is a pyrazolopyrimidine small molecule. PubMed+2PMC+2

  • It was identified in screens aimed at modulating “immortality” / telomere regulation. PubMed+1

Known Molecular Targets

  • Phosphoglycerate Kinase 1 (PGK1): A glycolytic enzyme. CRT0063465 binds to PGK1, with a measured KdK_dKd​ of ~24 µM. 

  • DJ-1 (PARK7): A stress-response protein / oxidative stress sensor. The compound also interacts with DJ-1. PMC

  • Moreover, there is evidence that PGK1 and DJ-1 physically interact (they form a complex), and CRT0063465 modulates this interaction. PubMed+1

Mechanism & Functional Effects

From the key study (Bilsland et al., Neoplasia, 2019): PubMed

  1. Binding to PGK1 alters conformation

    • CRT0063465 binds in the nucleotide-binding site of PGK1. PubMed

    • Structural data (X-ray crystallography) show that binding of CRT0063465 shifts PGK1 into an "open" conformation. PubMed

    • There’s a PDB structure of PGK1 bound to CRT0063465: PDB ID 5NP8. RCSB PDB

  2. Modulating Telomere Biology / Shelterin

    • PGK1 and DJ-1 were found to bind to TRF2, a core component of the telomere-protecting shelterin complex. PubMed+1

    • Treatment with CRT0063465 changes the composition of the shelterin complex (i.e., which proteins are associated), which suggests the compound influences telomere architecture. PMC

    • Under hypoglycemic stress (low glucose), CRT0063465 blocks telomere shortening in HCT116 cells. PubMed

    • Importantly, this effect is independent of telomerase activity—the compound does not work by reactivating telomerase. PMC

  3. Cytoprotective Effects

    • CRT0063465 provides protection against DNA-damage stress: in A2780 cells exposed to bleomycin, the compound reduces cytotoxicity. PMC

    • It also protects against toxicity from desferoxamine (DFO), which is an iron chelator, in these cells. PMC

Biological / Therapeutic Implications

  • The data suggest a cross-talk between metabolism (glycolysis) and telomere maintenance: by binding PGK1 and DJ-1, CRT0063465 influences how cells regulate telomeres under metabolic stress. PMC

  • Because telomere shortening is associated with aging, cellular stress, and cancer, modulating shelterin composition could have potential in chemoprevention or in diseases tied to telomere dysfunction. PubMed+1

  • Its cytoprotective effects under genotoxic stress (bleomycin) or iron-stress (DFO) hint at a potential role in protecting cells in stressful environments.

Limitations / Considerations

  • The compound’s affinity for PGK1 is relatively modest (Kd ~24 µM), so in vitro effects might require careful dosing. PubMed

  • Although there is structural data and some mechanistic insight, the full physiological role of the PGK1–DJ1 complex and how CRT0063465’s modulation translates in vivo is not fully established.

  • As of the key study, CRT0063465 is used in cell lines and in stress models; there's no (publicly disclosed) clinical development or therapeutic use.