Name: Prexasertib (LY2606368) Dihydrochloride
Brand: Selleck Chemicals
SKU: S7178
Rating: 5 (47 reviews)

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Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.88%

99.88

Produkter som ofta används tillsammans med Prexasertib (LY2606368) Dihydrochloride

Samotolisib (LY3023414)

The combination of it and LY3023414 results in tumor regression in OV-90 and Cov504 tumors and significantly enhanced efficacy when compared to singe agent.

Relaterade mål	CDK HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase
Övrigt Chk Inhibitorer	CCT245737 (SRA737) AZD7762 Rabusertib (LY2603618) MK-8776 (SCH 900776) CHIR-124 PF-477736 Prexasertib (LY2606368) BML-277 (Chk2 Inhibitor II) GDC-0575 SAR-020106

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer	Analystyp	Koncentration	Inkubationstid	Aktivitetsbeskrivning	PMID
HeLa cells	Function assay	33 or 100 nmol/L	7 hours	by 7 hours, a subpopulation of cells stained strongly for DSB by both TUNEL and pH2AX	26141948
U-2 OS cells	Function assay	4 nmol/L	24 h	a large shift in cell-cycle populations from G1 and G2–M to S-phase with an accompanied induction of H2AX phosphorylation.	26141948
CCRF-CEM parental cells	Function assay	10 nM	4 h	induced SLFN11 binding to chromatin and increased the chromatin binding of CDC45	29395061
SLFN11-del cells	Function assay	10 nM	4 h	induced SLFN11 binding to chromatin and increased the chromatin binding of CDC45	29395061
K562-WT	Function assay	100 nM	2 h	SLFN11, CDC45 and PCNA were enriched on nascent DNA	29395061
K562-E669Q	Function assay	100 nM	2 h	SLFN11, CDC45 and PCNA were enriched on nascent DNA	29395061
CCRF-CEM parental cells	Function assay	100 nM	2 h	SLFN11, CDC45 and PCNA were enriched on nascent DNA	29395061
HCT-116 cells	Function assay		10 days	inhibited both FANCD2 ubiquitination and increased Rad51 levels, significantly increased sensitivity of HCT-116 cells to F10	30439567
U937 cells	Function assay	3 nM		enhanced the cytotoxicity of CPX-351 at low nanomolar concentrations	30837643
KB-3-1	Function assay			P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	31515284
KB-8-5-11	Function assay			P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen, Potency = 1.2995 μM.	31515284
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt	438.31	Formel	C₁₈H₁₉N₇O₂.2HCl	Lagring (från mottagningsdatumet)	3 år-20°Cpulver
CAS-nr	1234015-54-3	Ladda ner SDF		Lagring av stamlösningar	1 år-80°Ci lösningsmedel 1 månad-20°Ci lösningsmedel
Synonymer	N/A			Smiles	COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N.Cl.Cl

Löslighet (Solubility)

In vitro
Batch:

DMSO : 17 mg/mL (38.78 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritetsräknare

Massa	Koncentration	Volym	Molekylvikt
=	×	×

Utspädningsräknare Molekylviktsräknare

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.
Clear solution	5%DMSO 1 Corn oil Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	0.500mg/ml (1.14mM)	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	0.800mg/ml (1.83mM)	Taking the 1 mL working solution as an example, add 50 μL of 16 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. 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.
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-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

Dosering: mg/kg Djurens medelvikt: g Doseringsvolym per djur:μL Antal djur:

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH₂O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC₅₀/Ki	Chk1 (Cell-free assay) 0.9 nM(Ki) Chk2 (Cell-free assay) 8 nM RSK (Cell-free assay) 9 nM
In vitro	In nonclinical studies, Prexasertib HCl (LY2606368) induced DNA damage as measured by replication catastrophe and increases in pH2A.X, a marker of double-stranded DNA breaks. Treatment of cells with this compound results in the rapid appearance of TUNEL and pH2AX-positive double-stranded DNA breaks in the S-phase cell population. In a functional assay, it potently abrogated the G2–M checkpoint activated by doxorubicin in p53-deficient HeLa cells with an EC50 of 9 nmol/L. It was broadly antiproliferative with IC50 values typically <50 nmol/L in the most sensitive cell lines with a minority of cell lines showing considerable resistance with IC50's >1,000 nmol/L. This compound requires CDC25A and CDK2 to cause DNA damage.
In vivo	Prexasertib HCl (LY2606368) inhibited tumor growth in cancer xenografts as monotherapy and in combination with other agents. In an orthotopic SKOV3 ovarian cancer model, it was shown to inhibit the growth of primary tumors and significantly reduce the incidence of metastases and ascites accumulation. This compound also demonstrated efficacy in an SW1990 orthotopic pancreatic cancer model resulting in a 92% inhibition of primary tumor growth and the elimination of metastases to the lymphnode, spleen, and intestine.
Referenser	[1] https://pubmed.ncbi.nlm.nih.gov/27044938/ [2] https://pubmed.ncbi.nlm.nih.gov/26141948/ [3] https://pubmed.ncbi.nlm.nih.gov/24140082/

Applikationer (Applications)

Metoder	Biomarkörer	PMID
Western blot	CHK1 / p-CHK1(Ser345) / γH2AX / Cleaved caspase3 pS6 (S235/236) / pS6 (S240/244)	28401005
Immunofluorescence	SLFN11 / CDC45 / EdU	29395061
Growth inhibition assay	Cell viability IC50	28401005

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer	Rekrytering	Tillstånd	Sponsor/Samarbetspartners	Startdatum	Faser
NCT04095221	Active not recruiting	Desmoplastic Small Round Cell Tumor\|Rhabdomyosarcoma	Memorial Sloan Kettering Cancer Center	September 17 2019	Phase 1\|Phase 2
NCT03495323	Completed	Cancer	Dana-Farber Cancer Institute\|Eli Lilly and Company	May 16 2018	Phase 1
NCT03414047	Completed	Ovarian Cancer	Eli Lilly and Company	April 10 2018	Phase 2
NCT03057145	Completed	Solid Tumor	Geoffrey Shapiro MD PhD\|Eli Lilly and Company\|AstraZeneca\|Dana-Farber Cancer Institute	March 10 2017	Phase 1

Vanliga frågor (Frequently Asked Questions)

Fråga 1:
Would you please suggest a suitable vehicle to dissolve it for in vivo use?

Svar:
It can be dissolved in a vehicle: 5% DMSO+40%PEG 300+5%Tween80+ddH2O for in vivo use in mice (i.p.). This stock concentration reaches 10mg/ml, and can be prepared for work solution as 0.5mg/ml, stable for no longer than 30min.

Fråga 2:
What is the solubility of it in 20% Captisol?

Svar:
It is a suspension in 20% Captisol, which is fine for oral gavage. You can dissolve this compound in this vehicle to the concentration you need as long as the suspension is homogeneous.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Prexasertib (LY2606368) Dihydrochloride CHK1-hämmare

Molekylvikt: 438.31

Kvalitetskontroll (Quality Control)

Produkter som ofta används tillsammans med Prexasertib (LY2606368) Dihydrochloride

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Vanliga frågor (Frequently Asked Questions)

Prexasertib (LY2606368) Dihydrochloride CHK1-hämmare

Molekylvikt: 438.31

Kvalitetskontroll (Quality Control)

Produkter som ofta används tillsammans med Prexasertib (LY2606368) Dihydrochloride

Cellodling, behandling & arbetskoncentration (Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Vanliga frågor (Frequently Asked Questions)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)