Delving into the Latest Updates on Galapagos SASU with Synapse

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Immune System Diseases

Digestive System Disorders

Small molecule drug

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Most frequently developed targets

Disease Domain	Count

Immune System Diseases	3
Infectious Diseases	1

Top 5 Drug Type	Count

Small molecule drug	5

Top 5 Target	Count

GPR84(G-protein coupled receptor 84)	3
IRAK4(Interleukin-1 receptor-associated kinase 4)	1
SIK1 x SIK2 x SIK3	1

OBJECTIVEThe selective Janus kinase 1 inhibitor filgotinib (GLPG0634), which is currently in clinical development for the treatment of rheumatoid arthritis (RA) and Crohn's disease, demonstrated encouraging safety and efficacy profiles in RA patients after 4 weeks of daily dosing. As RA patients might be treated with multiple medications simultaneously, possible drug-drug interactions of filgotinib with cytochrome P450 enzymes and with key drug transporters were evaluated in vitro and in clinical studies.METHODSThe enzymes involved in filgotinib's metabolism and the potential interactions of the parent and its active major metabolite with drug-metabolizing enzymes and drug transporters, were identified using recombinant enzymes, human microsomes, and cell systems. Furthermore, filgotinib's interaction potential with CYP3A4 was examined in an open-label study in healthy volunteers, which evaluated the impact of filgotinib co-administration on the CYP3A4-sensitive substrate midazolam. The potential interaction with the common RA drug methotrexate was investigated in a clinical study in RA patients.RESULTSIn vitro, filgotinib and its active metabolite at clinically relevant concentrations did not interact with cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases, and did not inhibit key drug transporters. In the clinic, a lack of relevant pharmacokinetic drug interactions by filgotinib and its active metabolite with substrates of CYP3A4, as well as with organic anion transporters involved in methotrexate elimination were found.CONCLUSIONthe collective in vivo and in vitro data on drug-metabolizing enzymes and on key drug transporters, support co-administration of filgotinib with commonly used RA drugs to patients without the need for dose adjustments.

01 May 2012·Bone

Genetic inactivation and pharmacological inhibition of IKKβ activity in cancer cells inhibit breast cancer-induced osteoclastogenesis, promotes osteoblast differentiation and prevents osteolysis

Author: S.H. Ralston ; B. Mognetti ; P. Mollat ; A.I. Idris ; J.G. Logan ; S. Marino

01 Feb 2012·Cellular OncologyQ2 · MEDICINE

BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β3 expression

Q2 · MEDICINE

ArticleOA

Author: Erik H. J. Danen ; Evangelia Pardali ; Geertje van der Horst ; Ella Nirmala ; Theo van Laar ; Hildegonda P. H. Naber ; Peter ten Dijke ; Anders Sundqvist ; Bertrand Heckmann ; Hans van Dam ; Gabri van der Pluijm ; Eliza Wiercinska

BACKGROUNDThe transforming growth factor (TGF)-β superfamily comprises cytokines such as TGF-β and Bone Morphogenetic Proteins (BMPs), which have a critical role in a multitude of biological processes. In breast cancer, high levels of TGF-β are associated with poor outcome, whereas inhibition of TGF-β-signaling reduces metastasis. In contrast, BMP-7 inhibits bone metastasis of breast cancer cells.METHODSIn this study, we investigated the effect of BMP-7 on TGF-β-induced invasion in a 3 dimensional invasion assay.RESULTSBMP-7 inhibited TGF-β-induced invasion of the metastatic breast cancer cell line MCF10CA1a, but not of its premalignant precursor MCF10AT in a spheroid invasion model. The inhibitory effect appears to be specific for BMP-7, as its closest homolog, BMP-6, did not alter the invasion of MCF10CA1a spheroids. To elucidate the mechanism by which BMP-7 inhibits TGF-β-induced invasion, we analyzed invasion-related genes. BMP-7 inhibited TGF-β-induced expression of integrin α(v)β(3) in the spheroids. Moreover, targeting of integrins by a chemical inhibitor or knockdown of integrin β(3) negatively affected TGF-β-induced invasion. On the other hand, overexpression of integrin β(3) counteracted the inhibitory effect of BMP7 on TGF-β-induced invasion.CONCLUSIONThus, BMP-7 may exert anti-invasive actions by inhibiting TGF-β-induced expression of integrin β(3).

100 Deals associated with Galapagos SASU

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100 Translational Medicine associated with Galapagos SASU

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Pipeline

Pipeline Snapshot as of 07 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

PSB-16671 ( GPR84 )	Fibrosis More	Preclinical
6-OAU ( GPR84 )	Fibrosis More	Preclinical
GLPG-3312 ( SIK1 x SIK2 x SIK3 )	Inflammation More	Preclinical
2-HTP ( GPR84 )	Fibrosis More	Preclinical
GLPG-2534 ( IRAK4 )	inflammatory dermatosis More	Preclinical