OTS964

OTS964 : Inhibitor of CDK11A

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe OTS964 is in the process of SERP review.

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Information

CDK11A

Inhibitor

up to 1 uM
Reviewer recommended concentration: At the highest concentration of 1 uM, keep in mind some inhibition (in vitro kinase data) might be possible of TOPK (IC50 = 353 nM), TYK2 (IC50 = 207 nM), PRK1 (IC50 = 508 nM) and CDK9 (IC50 = 538 nM), whereas 200 nM should be sufficient to very strongly inhibit CDK11A biochemically, and significantly influence cell-based activity, whereas this is relatively unlikely for other kinases.

Probe Availability:

In Vitro Validations

Uniprot ID: Q9UQ88

Target Class: Kinase

Target SubClass: CMGC

Potency: IC50

Potency Value: 10 nM

Potency Assay: In Vitro Kinase Assay assessing phosphorylation of Ser2 and Ser5 of RNAPII CTD

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

Target aliases:

Cyclin-dependent kinase 11A, PITSLREB, CDC2L3, CDC ...

DOI Reference: 10.1038/s41586-022-05204-z

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): OTS964 was profiled at 1 µM concentration in a panel of 412 human kinases (Eurofins) showing only 11 kinases, including CDK9, with more than a 50% reduction in the kinase activity. With IC50 values for these 11 kinases and 15 members of the CDK family were below 1 µM for only TYK2 (IC50 = 207 nM), PRK1 (IC50 = 508 nM) and CDK9 (IC50 = 538 nM).

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

OTS964 was originally reported as a PBK/TOPK inhibitor. Some references still refer to it in this context ([1] Yang Y et al. PBK/TOPK inhibitor OTS964 resistance is mediated by ABCB1-dependent transport function in cancer: in vitro and in vivo study. Molecular Cancer (2022) 21:40; https://doi.org/10.1186/s12943-022-01512-0; [2] Yang Y et al. OTS964, a TOPK Inhibitor, Is Susceptible to ABCG2-Mediated Drug Resistance. Frontiers in Pharmacology, February 2021 | Volume 12 | Article 620874. BRIEF RESEARCH REPORT published: 15 February 2021; doi: 10.3389/fphar.2021.620874), but it is more convincingly more potent and relatively selective for CDK11A (Mirella Bucci, Caitlin Deane, Grant Miura and Yiyun Song. CANCER THERAPY. Mistaken identity. Research Highlights. Nature Chemical Biology | VOL 15 | NOVEMBER 2019 | 1029 |. Commenting on: Sci. Trans. Med. 11, eaaw8412 (2019)). One caution I have is that is does contain a PAINS-like moiety, this being a p-hydroxy anilide, that could be set up to oxidize under certain conditions to a reactive p-quinoid-type compound. So thorough QC and good storage, use of fresh samples, recommended. Look for time-dependency bioactivity in a bioassay, and bioactivity increasing over time across a series of bioassay events.

(last updated: 8 Nov 2022 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

Based on the data found in the literature we can state that this compound can be a suitable selective inhibitor for CDK11. In vivo and cytotoxicity experiments are recommended to validate this probe. Other targets should be taken into consideration because of the cellular concentration from 200 to 500 nM. For example: CDK9 EGFR (L858R), EGFR (861Q), PRK1(h), TYK2(2).

(last updated: 23 May 2024 )

Change of use

Originally considered a TOPK inhibitor, OTS964 is a selective CDK11 inhibitor as shown in a recent publication, where the compound has been assessed in a broad Kinase panel.

(last updated: 21 Sept 2022)