Name: Ralimetinib (LY2228820) dimesylate
Brand: Selleck Chemicals
SKU: S1494
Rating: 5 (86 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.75%

99.75

Gerelateerde doelwitten	ERK Raf JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Overige p38 MAPK Inhibitoren	SB202190 SB203580 (Adezmapimod) PH-797804 Doramapimod (BIRB 796) VX-702 Losmapimod SB239063 Asiatic Acid Neflamapimod (VX-745) BMS-582949

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Formulering	Activiteitsbeschrijving	PMID
RPMI-8226	Kinase assay	~800 nM	DMSO	inhibits phosphorylation of HSP27	18397345
U266	Kinase assay	~800 nM	DMSO	inhibits phosphorylation of HSP27	18397345
MM.1S	Kinase assay	~800 nM	DMSO	inhibits phosphorylation of HSP27	18397345
RPMI-Dox40	Kinase assay	~800 nM	DMSO	inhibits phosphorylation of HSP27	18397345
RPMI-LR5	Kinase assay	~800 nM	DMSO	inhibits phosphorylation of HSP27	18397345
INA-6	Kinase assay	~800 nM	DMSO	inhibits phosphorylation of HSP27	18397345
RPMI-8226	Cytoxicity assay	~1000 nM	DMSO	no significant cytotoxicity	18397345
U266	Cytoxicity assay	~1000 nM	DMSO	no significant cytotoxicity	18397345
MM.1S	Cytoxicity assay	~1000 nM	DMSO	no significant cytotoxicity	18397345
RPMI-Dox40	Cytoxicity assay	~1000 nM	DMSO	no significant cytotoxicity	18397345
RPMI-LR5	Cytoxicity assay	~1000 nM	DMSO	no significant cytotoxicity	18397345
INA-6	Cytoxicity assay	~1000 nM	DMSO	no significant cytotoxicity	18397345
CD14+	Function assay	~800 nM	DMSO	inhibits osteoclastogenesis from CD14 positive cells	18397345
U-87-MG	Function assay	1 μM	DMSO	reduces tumor-driven cord formation	23335506
MDA-MB-231	Function assay	1 μM	DMSO	reduces tumor-driven cord formation	23335506
A-2780	Function assay	1 μM	DMSO	reduces tumor-driven cord formation	23335506
SK-OV-3	Function assay	1 μM	DMSO	reduces tumor-driven cord formation	23335506
LXFA-629	Function assay	1 μM	DMSO	reduces tumor-driven cord formation	23335506
NCI-H1650	Function assay	1 μM	DMSO	reduces tumor-driven cord formation	23335506
PC-3	Function assay	1 μM	DMSO	reduces tumor-driven cord formation	23335506
RAW264.7	Function assay	~20 μM	DMSO	inhibits Anisomycin-stimulated MK2 phosphorylation with IC50 of 35.3 nM	24356814
mouse peritoneal macrophages	Function assay	~20 μM	DMSO	LPS/IFN-γ–stimulated TNF-α production with IC50 of 6.3 nM	24356814
A549	Function assay	~20 μM	DMSO	inhibits LPS-induced CXCL8 production with IC50 of 144.9 nM	24356814
MDA-231	Function assay	~10 μM		suppresses DKK-1 expression	26407843
MCF-7	Function assay	~10 μM		suppresses DKK-1 expression	26407843
MDA-435	Function assay	~10 μM		suppresses DKK-1 expression	26407843
PC3	Function assay	~10 μM	DMSO	suppresses DKK-1 expression	26913608
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Klik om meer experimentele gegevens over de cellijn te bekijken

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	612.74	Formule	C₂₄H₂₉FN₆.2CH₄O₃S	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	862507-23-1	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	CC(C)(C)CN1C2=C(C=CC(=N2)C3=C(N=C(N3)C(C)(C)C)C4=CC=C(C=C4)F)N=C1N.CS(=O)(=O)O.CS(=O)(=O)O

Oplosbaarheid (Solubility)

In vitro
Batch:

Water : 123 mg/mL

DMSO : 35 mg/mL (57.12 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 3 mg/mL

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	Saline Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	30.000mg/ml (48.96mM)	Taking the 1 mL working solution as an example, add 30 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	p38α (Cell-free assay) 7 nM
In vitro	LY2228820 inhibits p38α, as well as the level of phosphoMAPKAPK-2 (pMK2) in RAW 264.7 cells, with IC50 values of 7 nM and 34.3 nM, respectively. Furthermore, LY2228820 inhibits lipopolysaccharide (LPS)-induced TNFα formation in murine peritoneal macrophages, with IC50 of 5.2 nM. In multiple myeloma (MM) cells, including INA6, RPMI-8226, U266, and RPMI-Dox40, LY2228820 (200 nM–800 nM) significantly blocks p38MAPK signaling, as revealed by its inhibition on phosphorylation of HSP27, a downstream target of p38MAPK, without affecting the expression level of HSP27. LY2228820 (200 nM–400 nM) enhances cytotoxicity and apoptosis, but LY2228820 alone doesn't inhibit the growth of MM.1S cells. LY2228820 (200 nM–800 nM) also inhibits secretion of IL-6 and MIP-1α in long-term BM stromal cells (LT-BMSCs), BM mononuclear cells (BMMNCs), peripheral blood (PB) CD138⁺, CD138⁻ or PB CD14⁺ cells. LY2228820 (400 nM–800 nM) also blocks osteoclastogenesis from CD14⁺ cells.
Kinase Assay	Remming van p38α
Kinase Assay	Remming van p38α wordt bepaald met recombinant humaan p38α in een standaard filterbindingsprotocol met ATP[γ-³³P] en EGFR 21-mer peptide als substraat. Functionele remming van TNFα in murine peritoneale macrofagen wordt bepaald met LPS-stimulatie in aanwezigheid van LY2228820. Om de p38α-activiteit in cellen directer te beoordelen, worden RAW 264.7-cellen behandeld met LY2228820 en vervolgens gestimuleerd met anisomycine. Het niveau van p38α-activiteit wordt gedetecteerd met een phosphoMAPKAPK-2 (pMK2) (Thr 334) antilichaam dat reageert met een residu dat specifiek gefosforyleerd is door p38α.
In vivo	In LPS-induced mice, LY2228820 effectively inhibits the formation of TNFα with a threshold minimum 50% effective dose (TMED₅₀) less than 1 mg/kg. In a rat model of collagen-inducedarthritis (CIA), LY2228820 displays potent effects on paw swelling, bone erosion, and cartilage destruction, with a threshold minimum 50% effective dose (TMED₅₀)of 1.5 mg/kg.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/18039577/ [2] https://pubmed.ncbi.nlm.nih.gov/18397345/ [3] https://pubmed.ncbi.nlm.nih.gov/15940263/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	p-p38 / p38α / p38β / p-MK2 / MK2 / p-HSP27 / HSP27 p-S6K		23335506

Informatie klinische proef (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2019-08-14)

NCT-nummer	Rekrutering	Aandoeningen	Sponsor/Medewerkers	Startdatum	Fasen
NCT02364206	COMPLETED	Adult Glioblastoma	Centre Jean Perrin	2015-06-08	PHASE1; PHASE2
NCT01663857	COMPLETED	Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer	Eli Lilly and Company	2012-07	PHASE1; PHASE2
NCT02860780	COMPLETED	Advanced Cancer; Metastatic Cancer; Colorectal Cancer; Non-small Cell Lung Cancer	Eli Lilly and Company	2016-08-10	PHASE1
NCT02322853	TERMINATED	Postmenopausal; Metastatic Breast Cancer	Centre Francois Baclesse	2015-01	PHASE2
NCT02860780	Completed	Advanced Cancer\|Metastatic Cancer\|Colorectal Cancer\|Non-small Cell Lung Cancer	Eli Lilly and Company	2016-08-10	Phase 1
NCT02364206	Completed	Adult Glioblastoma	Centre Jean Perrin\|National Cancer Institute France\|ARC Foundation for Cancer Research	2015-06-08	Phase 1\|Phase 2

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Ralimetinib (LY2228820) dimesylate p38 MAPK Remmer

Moleculair gewicht: 612.74

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Ralimetinib (LY2228820) dimesylate p38 MAPK Remmer

Moleculair gewicht: 612.74

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Informatie klinische proef (Clinical Trial Information)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)