Delving into the Latest Updates on SB-743921 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

KIF11

Action

inhibitors

Mechanism

KIF11 inhibitors(Kinesin-like protein 1 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication-

Inactive Indication

Aggressive Non-Hodgkin LymphomaHodgkin's LymphomaSolid tumor

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

License Organization

Drug Highest PhasePendingPhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC31H33ClN2O3

InChIKeyPGXYIBJJCLWJST-MUUNZHRXSA-N

CAS Registry618430-39-0

This study was an early-phase trial arranged into two phases. The Phase I portion was a dose-escalation study designed to assess the safety, tolerability and to identify the maximum tolerated dose of SB-743921 in patients with Non-Hodgkin Lymphoma and Hodgkin Lymphoma. Phase II was intended to assess the activity, safety and tolerability of SB-743921 in patients with Indolent and Aggressive Non-Hodgkin's Lymphomas exclusively. The Phase II portion of the study was not initiated.

Start Date01 Apr 2006

Sponsor / Collaborator

Cytokinetics, Inc.

NCT00136513

/ CompletedPhase 1

A Phase I Study to Determine the Safety and Pharmacokinetics of Intravenous Administration of SB743921 on a Once Every 3 Week Schedule in Patients With Solid Tumors

The purpose of this study is to find a dose of SB-743921 in adult patients with solid tumors or lymphoma who have progressed on standard therapy or who have relapsed. SB-743921 is dosed by 1-hour intravenous infusion every 3 weeks. A patient may continue to receive treatment as long as they are benefiting from the treatment. Blood samples will be taken at specific times to measure the amount of the drug in your body at specific times after the drug is given. Blood samples will also be taken for lab tests such as complete blood counts and clinical chemistries. Physical exams will be performed before each treatment with SB-743921. During the treatment phase, the patients will undergo regular assessments for safety and clinical response.

Start Date01 Apr 2004

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with SB-743921

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100 Translational Medicine associated with SB-743921

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100 Patents (Medical) associated with SB-743921

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75

Literatures (Medical) associated with SB-743921

01 Sep 2024·Journal of Molecular Structure

Identification, characterization and biological studies of kinesine spindle protein inhibitor, benzo[b][1,4]oxazine-6-carboxamide derivative, via 3D-pharmacophore virtual screening

Author: Elseginy, Samia A.

Kinesin spindle protein (Eg5) has been widely studied, as an important target for developing chemotherapy drugs, due to its essential role in mitotic spindle formation in mitosis.In this study, we target a promising novel allosteric site involving α4 and α6 helixes, which is located 15 Å from the allosteric ispinesib site.An extensive 3D-Pharmacophore structure based virtual screening was conducted.Mol. docking was carried out to explore a library of com. mols.Eleven compounds were identified with diversity in their chem. scaffold.Biol. evaluation and MT ATPase assays revealed that compound 11 with scaffold N-(2- (2, 6 -dimethylphenoxy) phenyl) -3, 4-dihydro -3-oxo -2H-benzo[b][1,4]oxazine-6-carboxamide inhibits Eg5 activity at (IC₅₀ = 1.37 ± 0.15 μM).The chem. structure of compound 11 was confirmed by ¹H NMR and mass spectral data.The stability of compound 11 within the Eg5-ADP/ATP complex was investigated using mol. dynamic simulation technique.The free binding energy was calculated using MM/PBSA.

01 Jun 2024·Archives of Biochemistry and Biophysics

Binding patterns of inhibitors to different pockets of kinesin Eg5

Article

Author: Geng, Yizhao ; Huo, Ziling ; Jia, Ning ; Zhang, Bingbing ; Ji, Qing ; Qin, Jingyu

The kinesin-5 family member, Eg5, plays very important role in the mitosis. As a mitotic protein, Eg5 is the target of various mitotic inhibitors. There are two targeting pockets in the motor domain of Eg5, which locates in the α2/L5/α3 region and the α4/α6 region respectively. We investigated the interactions between the different inhibitors and the two binding pockets of Eg5 by using all-atom molecular dynamics method. Combined the conformational analysis with the free-energy calculation, the binding patterns of inhibitors to the two binding pockets are shown. The α2/L5/α3 pocket can be divided into 4 regions. The structures and binding conformations of inhibitors in region 1 and 2 are highly conserved. The shape of α4/α6 pocket is alterable. The space of this pocket in ADP-binding state of Eg5 is larger than that in ADP·Pi-binding state due to the limitation of a hydrogen bond formed in the ADP·Pi-binding state. The results of this investigation provide the structural basis of the inhibitor-Eg5 interaction and offer a reference for the Eg5-targeted drug design.

01 May 2024·Journal of Cellular and Molecular Medicine

Prognostic and immunotherapeutic implications of bilirubin metabolism‐associated genes in lung adenocarcinoma

Article

Author: Li, Zeyao ; Ling, Xiean ; Huang, Tonghai ; Ren, Kangqi ; Chen, Lin

AbstractLung adenocarcinoma (LUAD) is a major subtype of non‐small‐cell lung cancer and accompanies high mortality rates. While the role of bilirubin metabolism in cancer is recognized, its specific impact on LUAD and patient response to immunotherapy needs to be elucidated. This study aimed to develop a prognostic signature of bilirubin metabolism‐associated genes (BMAGs) to predict outcomes and efficacy of immunotherapy in LUAD. We analysed gene expression data from The Cancer Genome Atlas (TCGA) to identify survival‐related BMAGs and construct a prognostic model in LUAD. The prognostic efficacy of our model was corroborated by employing TCGA‐LUAD and five Gene Expression Omnibus datasets, effectively stratifying patients into risk‐defined cohorts with marked disparities in survival. The BMAG signature was indeed an independent prognostic determinant, outperforming established clinical parameters. The low‐risk group exhibited a more favourable response to immunotherapy, highlighted by increased immune checkpoint expression and immune cell infiltration. Further, somatic mutation profiling differentiated the molecular landscapes of the risk categories. Our screening further identified potential drug candidates preferentially targeting the high‐risk group. Our analysis of critical BMAGs showed the tumour‐suppressive role of FBP1, highlighting its suppression in LUAD and its inhibitory effects on tumour proliferation, migration and invasion, in addition to its involvement in cell cycle and apoptosis regulation. These findings introduce a potent BMAG‐based prognostic indicator and offer valuable insights for prognostication and tailored immunotherapy in LUAD.

100 Deals associated with SB-743921

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Aggressive Non-Hodgkin Lymphoma	Phase 2	United States	Cytokinetics, Inc.	01 Apr 2006
Aggressive Non-Hodgkin Lymphoma	Phase 2	Russia	Cytokinetics, Inc.	01 Apr 2006
Hodgkin's Lymphoma	Phase 2	Russia	Cytokinetics, Inc.	01 Apr 2006
Hodgkin's Lymphoma	Phase 2	United States	Cytokinetics, Inc.	01 Apr 2006
Solid tumor	Phase 2	United States	GSK Plc	01 Apr 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00343564 (Pubmed \| Leuk Lymphoma)	Phase 1/2	Lymphoma	-	SB-743921	(ioagneywmb) = ldaudmzcau ohghxvlwsx (zngryndwgu )	-	02 Sep 2015
NCT00343564 (Pubmed \| Leuk Lymphoma)	Phase 1/2	Lymphoma	-	SB-743921 + G-CSF	(ioagneywmb) = whjzuuunka ohghxvlwsx (zngryndwgu )	-	02 Sep 2015
ASCO2009	Phase 1/2	Hodgkin's Lymphoma \| Non-Hodgkin Lymphoma	51	SB-743921	(igtpvfnykc) = uzkbtsvxpa wychycwpwd (iehizauerp )	-	20 May 2009
ASCO2008	Phase 1/2	Hodgkin's Lymphoma	32	SB-743921	(lqrjzcgmlb) = kdfkyklolw mrlrensath (itidrduxjx ) View more	-	20 May 2008
ASCO2006	Phase 1	Solid tumor	44	SB-743921	vyjppmjwfd(ltosyiyyeg) = zaosltquqc zyytctmdii (djkexnnkyr ) View more	-	20 Jun 2006