Delving into the Latest Updates on Seliciclib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine, R-roscovitine, CYC 202

+ [2]

Target

CDK2 x CDK7 x CDK9

Action

inhibitors

Mechanism

CDK2 inhibitors(Cyclin-dependent kinase 2 inhibitors), CDK7 inhibitors(Cyclin-dependent kinase 7 inhibitors), CDK9 inhibitors(Cyclin-dependent kinase 9 inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesEndocrinology and Metabolic Disease+ [4]

Active Indication

Cushing SyndromeNasopharyngeal NeoplasmsNon-Small Cell Lung Cancer+ [1]

Inactive Indication

Advanced Malignant Solid NeoplasmBreast CancerCOVID-19+ [6]

Originator Organization

Centre National de la Recherche Scientifique

Active Organization

Centre National de la Recherche Scientifique

ManRos Therapeutics SA

Cyclacel Pharmaceuticals, Inc.

+ [1]

Inactive Organization-

License Organization

The University of Edinburgh

Cyclacel Pharmaceuticals, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC19H26N6O

InChIKeyBTIHMVBBUGXLCJ-OAHLLOKOSA-N

CAS Registry186692-46-6

A Phase II, Dose Ranging, Multicenter, Double-blind, Placebo Controlled Study to Evaluate Safety and Effects of (R)-Roscovitine in Adults Subjects With Cystic Fibrosis, Carrying 2 Cystic Fibrosis Causing Mutations With at Least One F508del-CFTR Mutation and Chronically Infected With Pseudomonas Aeruginosa, a Study Involving 36 CF Patients (24 Treated, 12 Controls). ROSCO-CF.

This is a phase II, dose ranging, multicenter, randomized, double-blind, placebo-controlled study.
The aim of this study is to assess the safety of increasing doses of roscovitine administered orally for 4 cycles of 4 consecutive days (treatment "on") separated by a 3 days treatment free period (treatment "off") in adult CF subjects with Cystic Fibrosis carrying 2 Cystic Fibrosis causing mutations with at least one F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa.
This study involved 36 Cystic Fibrosis patients: 24 treated and 12 controls.

Start Date22 Feb 2016

Sponsor / Collaborator

University Hospital of Brest

[+2]

EUCTR2015-002911-13-FR

/ Not yet recruitingPhase 2IIT

A Phase II, dose ranging, multicenter, double-blind, placebo controlled study to evaluate safety and efficacy of (R)-roscovitine in subjects with Cystic Fibrosis, homozygous for the F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa, a study involving 36 CF patients (24 treated, 12 controls). - ROSCO-CF

Start Date15 Sep 2015

Sponsor / Collaborator-

100 Clinical Results associated with Seliciclib

Login to view more data

100 Translational Medicine associated with Seliciclib

Login to view more data

100 Patents (Medical) associated with Seliciclib

Login to view more data

1,873

Literatures (Medical) associated with Seliciclib

01 Aug 2025·JOURNAL OF MOLECULAR STRUCTURE

Pyrazolopyrimidine fused thiazolidinone hybrids as CDK2 inhibitors: insights from pharmacophore modeling, docking, DFT and molecular dynamics simulations

Author: Altharawi, Ali ; Alotaibi, Saad H. ; Oubella, Ali ; Chagaleti, Bharath Kumar ; Saravanan, Venkatesan ; Mk, Kathiravan

Cancer remains a significant global health challenge, primarily driven by the dysregulation of key cellular pathways, including kinase-mediated signaling.Cyclin-dependent kinases (CDKs), particularly CDK2, play a crucial role in regulating the cell cycle and tumor progression, making them attractive targets for anticancer drug development.Pyrazolopyrimidines, known as bioisosteres of purines, exhibit potent kinase inhibitory activity by selectively targeting ATP-binding sites.The mol. hybridization of pyrazolopyrimidines with thiazolidinones provides a rational strategy for designing novel CDK2 inhibitors with enhanced selectivity and therapeutic potential.In this study, 30 hybrid compounds (PPT1-30) were designed to target CDK2.A ligand-based pharmacophore model was constructed using a training set of six potent CDK2 inhibitors, resulting in a robust model featuring one Aro/Hyd and three Acc/Don pharmacophore features.Virtual screening led to the identification of 13 potential hits from the 30 hybrids.The top 10 compounds underwent further mol. docking anal., revealing docking scores ranging from -7.2 to -8.2 kcal/mol, with PPT15 demonstrating the highest potency (-8.2 kcal/mol), surpassing the standard CDK2 inhibitor Roscovitine (-8.0 kcal/mol).ADMET anal. of the top 10 compounds showed favorable pharmacokinetic and toxicity profiles, aligning well with drug-like properties.D. Functional Theory (DFT) anal. further confirmed the superior electronic properties of PPT15, with a high energy gap (0.2804 eV), enhancing receptor interactions.Mol. dynamics simulations over 500 ns validated the stability of the CDK2-PPT15 complex, maintaining minimal RMSD (protein: 2.0-3.2 Å, ligand: 2.8-4.8 Å), low RMSF (<1.8 Å protein, <1.5 Å ligand), and strong interactions with key residues such as Leu83, Lys33, Lys89, Ala31, and Val18.MMGBSA anal. revealed a higher binding affinity (-34.794 kcal/mol), stronger Coulombic interactions (-26.2546 kcal/mol), and improved hydrogen bonding (-1.52033 kcal/mol) for PPT15.Post-dynamic simulation anal. of PPT15 at various time frames (200, 400, 600, 800, and 1000 ns) further demonstrated stable interactions with residues Leu83, Asp145, Lys33, and Lys89, ensuring its stability within the binding pocket.These overall key findings revealed that PPT15 is a potent CDK2 inhibitor.

01 Jun 2025·ANALYTICAL BIOCHEMISTRY

A sensitive HPLC method with fluorescence detection for quantification of pemigatinib in human plasma samples and its in-vivo application to pharmacokinetic study in rats

Article

Author: Darwish, Ibrahim A ; Alzoman, Nourah Z ; Alrubia, Sarah ; Alsegiani, Amsha S

Cholangiocarcinoma is a lethal tumour of the bile ducts. Cholangiocarcinoma fibroblast growth factor receptor gene fusions forms can be targeted by Pemigatinib (PGT). PGT a recently approved kinase inhibitor by the US-FDA, has its approval accelerated due to the disease viciousness. Development of a sensitive yet available and economical analytical platform to quantify PGT in human plasma is genuinely needed. Enabling monitoring of the therapeutic plan, hence, ensuring the drug efficacy and safety through pharmacokinetic studies. High-performance liquid chromatography with fluorescence detector (HPLC-FD) method is proposed using the native fluorescence of PGT. PGT and seliciclib (internal standard) chromatographic conditions optimisation, revealed favourable use of isocratic mobile phase consisting of methanol:ammonium acetate buffer (70:30v/v, pH5.0) pumped into C18-column (150 mm length × 4.6 mm internal diameter, 5 μm particle size), at 1 mL min^-1 flow rate. PGT and seliciclib fluorescence excitation and emission were measured at 280 and 360 nm, respectively. Validation of the HPLC-FD method was processed based on the International Council for Harmonization guidelines. The method linearity range was 5-300 ng mL^-1. The limits of detection and quantification were 2.8 and 8.5 ng mL^-1, respectively. High precision and accuracy indicated by relative standard deviation ≤ 5.2, and recovery values of 95.4-102.2 %. Evident of the method greenness was verified by green analytical chemistry metric tools. HPLC-FD method was successfully applied to study PGT pharmacokinetics in rats. In conclusion, this study introduces a reliable analytical method of PGT in plasma for routine use in therapeutic drug monitoring for quality assurance and clinical follow-up.

01 Jun 2025·JOURNAL OF MOLECULAR STRUCTURE

Synthesis, computational analysis, and exploring antiproliferative activity of triazolo- and thiazolo-pyrimidine derivatives as potential EGFR inhibitors

Author: Abdelrahman, Ali H. ; Ramadan, Sayed K. ; Hegazy, Mohamed A. ; Labena, Ahmed ; Alzahrani, Abdullah Y. A. ; Azab, Mohammad E.

Anticancer drug acquiring usually discloses with an in vitro testing in cell panels to certainly detect the lead compoundsEGFR is a tyrosine kinase cell surface receptor that plays a key function in signal transduction processes and is observed on most cell surfaces.One of the promising frameworks in drug detection is pyrimidine and its fused heteroannulated bicyclic derivatives which exhibited promising anticancer activity.The prepared triazolopyrimidine and thiazolopyrimidine derivatives were proposed to fit into the ATP binding site of EGFR protein.The in vitro antiproliferative screening against MCF7 and HCT116 cancer cell panels disclosed the most influence of triazolopyrimidine 3, thiazolopyrimidine 9, and pyrimidinethione 1 compared to the reference drug, roscovitine (imidazopyrimidine hybrid).The inhibitory action of the most promising compounds was explored vs. EGFR enzyme, which displayed the highest efficacy of triazolopyrimidine 3 compared to the standard drug (erlotinib).The structure-activity relationship (SAR) probe demonstrated that specific structural modifications had a significant impact on the antiproliferative action.In silico mol. docking was performed on these promising compounds vs. EGFR enzyme (breast cancer protease, PDB ID: 3W32) to show the enzyme-inhibitor interactions, which uncovered the superlative binding interactions of triazolopyrimidine 3 with key nucleobases and amino acids of EGFR kinase.Among DFT calculations, ELUMO of compounds 3< 1< 9, which enriched its binding affinity of with nucleophilic receptor's active pockets.Regarding ADME simulation, they had gastrointestinal tract (GIT) absorption, good bioavailability score, and worthy lead-likeness.This work may contribute to developing new effective EGFR inhibitor.

100 Deals associated with Seliciclib

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	Seliciclib	-	DB06195

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cushing Syndrome	Phase 2	United States	Cedars-Sinai Medical Center	02 Nov 2018
Cystic Fibrosis	Phase 2	France	ManRos Therapeutics SA	22 Feb 2016
Cystic Fibrosis	Phase 2	France	Cyclacel Pharmaceuticals, Inc.	22 Feb 2016
Pseudomonas Infections	Phase 2	France	ManRos Therapeutics SA	22 Feb 2016
Pseudomonas Infections	Phase 2	France	Cyclacel Pharmaceuticals, Inc.	22 Feb 2016
Rheumatoid Arthritis	Phase 2	United Kingdom	-	24 Mar 2015
Nasopharyngeal Carcinoma	Phase 2	United States	Cyclacel Pharmaceuticals, Inc.	27 Nov 2007
Nasopharyngeal Carcinoma	Phase 2	European Union	Cyclacel Pharmaceuticals, Inc.	27 Nov 2007
Non-Small Cell Lung Cancer	Phase 2	United States	Cyclacel Pharmaceuticals, Inc.	09 Aug 2006
Breast Cancer	Phase 2	Belgium	-	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02160730 (CTgov)	Phase 2	Pituitary ACTH Hypersecretion	4	R-roscovitine	zubdqnccrk = bxznzfgaiq vvwqafsjrg (jurtgovczv, jhmhzfzenp - uzvuytsgqd) View more	-	29 Oct 2021
TRAFIC (EULAR2020)	Phase 1	Rheumatoid Arthritis	15	Seliciclib	tauuxlbaqc(lsbojdlowm) = 6 patients experienced DLTs, of which two were classified as serious AEs (SAEs) in keeping with the safety profile of seliciclib; these are summarised in Table 1. Of 43/65 total AEs reported at any dose that did not contribute to a DLT, 26 were possibly, probably or definitely related to seliciclib; 19 of these 26 were mild, 7 moderate and none severe. The most frequent AE was mild nausea. qbsfcsfnmc (ysuwikecwl )	Positive	03 Jun 2020
ASTRO2010	Not Applicable	DNA Damage	-	Seliciclib (S)	rvzaodhzzy(zwdzlcuusw) = qzedrrxpzl dbhmhhdlnp (flayhqlykv )	-	01 Nov 2010