INX-315

INX-315 : Inhibitor of CDK2

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe INX-315 is in the process of SERP review.

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Information

CDK2

Inhibitor

up to 1 uM
Reviewer recommended concentration: 100 nM

In Vitro Validations

Uniprot ID: P24941

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 0.6 nM

Potency Assay: Nanosyn biochemical assay CDK2/Cyclin E1

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Cyclin-dependent kinase 2, CDKN2, CDK2, CDK2_HUMAN ...

DOI Reference: 10.1158/2159-8290.CD-23-0954

Uniprot ID: P24941

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 2.5 nM

Potency Assay: Nanosyn biochemical assay CDK2/Cyclin A2

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Cyclin-dependent kinase 2, CDKN2, CDK2, CDK2_HUMAN ...

DOI Reference: 10.1158/2159-8290.CD-23-0954

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): The intracellular IC50 (NanoBRET) for INX-315 and CDK1/cyclin B1 was 374 nM while the IC50 for CDK9/cyclin T1 was 2,950 nM.

Potency assay (off target): Selectivity within family (IC50): CDK1/B1 30 nM, CDK2/cyclin E1 0.6 nM, CDK2/cyclin A2 2.5 nM, CDK3/cyclin E1 15.1 nM, CDK4/cyclin D1 125 nM, CDK5 23.1 nM, CDK5/p25 21.4 nM, CDK6/cyclin D3 349 nM, CDK7 >10000 nM, CDK9/cyclin T1 62 nM Broader kinase selectivity profile of INX-315 was assessed using the LanthaScreen Eu Kinase Binding and Z’-Lyte Kinase Assays. Treatment with 100 nM INX-315 caused ≥94% inhibition of CDK2/cyclin A/A1/E1/O and caused ≥80% inhibition of CDK3/cyclin E1, CDK5 (inactive), CDK5/p25, CDK5/p35, colony stimulating factor 1 receptor (CSF1R), MAPK15/ERK7, neurotrophic tyrosine receptor kinase (NTRK)/tyrosine receptor kinase (TRK)C, and tyrosine receptor kinase (TYK)2. Follow-up experiments showed INX-315 displayed selectivity for CDK2/cyclin A1/E1/O with IC50 values of 4 nM or less. CSF1R had an IC50 of 2.29 nM, while all other targets had IC50 values greater than 10 nM.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

SERP+ Comments:

Based on the data, CSF1R should be considered as off-target. This probe, unfortunately does not have an inactive control compound, but PF-07104091 can be used as orthogonal probe for CDK2, with good off-target profile within the CDK family.

(last updated: 17 Jun 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

While this probe is touted as highly selective for CDK2, it will depend on the setting and the biology, e.g. the corresponding cyclin partner, whether selectivity can be considered significant enough to not be of concern. While much discussion comes from CDK1, there are also some concerns with CDK3 and CDK5, where the reported selectivity is modest. Some of the cellular d.r. data has been (and should be) attributed to 'potentially hitting targets other than CDK2'; CSF1R should also be kept in mind. Overall INX-315 is one of the better CDK2 tools in the public domain, but should be used a) in conjunction with PF-07104091 and b) at a d.r. range in cells up to 100 nM (preferably) keeping in mind that at concentrations above 300 nM there might be significant contributions from other CDKs. Some of the published data also indicates in vivo use in mice is feasible for this molecule at 100 mpk/bid.

(last updated: 1 Jul 2024 )