Source 1primary paper2020ACS Chemical Biology
Toolkit/CIB1 helix 10 pocket
CIB1 helix 10 pocket
Also known as: CIB1 H10 pocket
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The CIB1 helix 10 pocket is a ligandable site in calcium and integrin binding protein 1 (CIB1) identified as the binding site for the peptide inhibitor UNC10245092. In the cited 2020 ACS Chemical Biology study, UNC10245092 bound this pocket with low nanomolar affinity and acted as a first-in-class chemical tool site for CIB1 inhibition in cell culture.
Usefulness & Problems
Why this is useful
This pocket is useful as a chemically addressable site for perturbing CIB1, a target for which the cited study developed a probe molecule. Tat-derived cell-penetrating versions of UNC10245092 produced effects in triple-negative breast cancer cell culture consistent with CIB1 depletion, supporting use of the pocket for intracellular target engagement studies.
Source:
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
Problem solved
The CIB1 H10 pocket helps solve the problem of how to chemically inhibit CIB1 through a defined and structurally characterized binding site. The cited work specifically addressed production of a probe molecule to the CIB1 helix 10 pocket and validation of that site in cell culture.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Mechanisms
alpha-helical pocket bindingcompetitive displacement of the cib1 c-terminal h10 helixconformational uncagingConformational UncagingTechniques
No technique tags yet.
Target processes
No target processes tagged yet.
Input: Chemical
Implementation Constraints
The validated ligand described in the evidence is the peptide inhibitor UNC10245092, including a Tat-derived cell-penetrating peptide derivative for cellular studies. Structural data indicate that productive binding requires alpha-helical engagement of the CIB1 H10 pocket and competitive displacement of the endogenous C-terminal H10 helix. No additional requirements such as cofactors, expression systems, or delivery modalities beyond CPP derivatization are specified in the supplied evidence.
The evidence provided comes from a single 2020 study and supports cell-culture validation rather than broader in vivo or multi-system validation. The available evidence does not report independent replication, detailed selectivity profiling, or practical performance beyond Tat-derived peptide delivery.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
UNC10245092 binds CIB1 with low nanomolar affinity.
Both assays showed that the peptide bound to CIB1 with low nanomolar affinity.
binding affinity low nanomolar
UNC10245092 binds CIB1 with low nanomolar affinity.
Both assays showed that the peptide bound to CIB1 with low nanomolar affinity.
binding affinity low nanomolar
UNC10245092 binds CIB1 with low nanomolar affinity.
Both assays showed that the peptide bound to CIB1 with low nanomolar affinity.
binding affinity low nanomolar
UNC10245092 binds CIB1 with low nanomolar affinity.
Both assays showed that the peptide bound to CIB1 with low nanomolar affinity.
binding affinity low nanomolar
UNC10245092 binds CIB1 with low nanomolar affinity.
Both assays showed that the peptide bound to CIB1 with low nanomolar affinity.
binding affinity low nanomolar
UNC10245092 binds CIB1 with low nanomolar affinity.
Both assays showed that the peptide bound to CIB1 with low nanomolar affinity.
binding affinity low nanomolar
UNC10245092 binds CIB1 with low nanomolar affinity.
Both assays showed that the peptide bound to CIB1 with low nanomolar affinity.
binding affinity low nanomolar
Tat-derived CPP-derivatized UNC10245092 shows effects on TNBC cells in culture that are consistent with CIB1 depletion.
UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion.
Tat-derived CPP-derivatized UNC10245092 shows effects on TNBC cells in culture that are consistent with CIB1 depletion.
UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion.
Tat-derived CPP-derivatized UNC10245092 shows effects on TNBC cells in culture that are consistent with CIB1 depletion.
UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion.
Tat-derived CPP-derivatized UNC10245092 shows effects on TNBC cells in culture that are consistent with CIB1 depletion.
UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion.
Tat-derived CPP-derivatized UNC10245092 shows effects on TNBC cells in culture that are consistent with CIB1 depletion.
UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion.
Tat-derived CPP-derivatized UNC10245092 shows effects on TNBC cells in culture that are consistent with CIB1 depletion.
UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion.
Tat-derived CPP-derivatized UNC10245092 shows effects on TNBC cells in culture that are consistent with CIB1 depletion.
UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion.
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
structure resolution 2.1 Å
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
structure resolution 2.1 Å
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
structure resolution 2.1 Å
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
structure resolution 2.1 Å
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
structure resolution 2.1 Å
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
structure resolution 2.1 Å
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
structure resolution 2.1 Å
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
Approval Evidence
1 source2 linked approval claimsfirst-pass slug cib1-helix-10-pocket
To produce a probe molecule to the CIB1 helix 10 (H10) pocket
Source:
structural mechanismsupports
UNC10245092 binds as an alpha-helix in the CIB1 H10 pocket and displaces the CIB1 C-terminal H10 helix, causing conformational changes in H7 and H8.
the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8
Source:
tool classificationsupports
The studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.
Source:
Comparisons
Source-backed strengths
UNC10245092 was reported to bind CIB1 with low nanomolar affinity, indicating strong biochemical engagement of the H10 pocket. Structural characterization showed that the peptide binds as an alpha-helix in the pocket and displaces the C-terminal H10 helix while inducing conformational changes in helices H7 and H8, providing a clear mechanistic basis for inhibition. A Tat-derived cell-penetrating derivative showed cell-culture phenotypes consistent with CIB1 depletion in TNBC cells.
Ranked Citations
- 1.