Prexasertib dimesylate - Moligand™, ≥99% , CAS No.1234015-58-7

CAS: 1234015-58-7 Cat. No.: P651249 Summenformel: C₂₀H₂₇N₇O₈S₂ Molekulargewicht: 557.60 PubChem CID: 137364590

GRADE & PURITY Moligand™, ≥99%

Synonyms

5-((5-(2-(3-Aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile dimethanesulfonate | SCHEMBL20591301 | CS-0130202

Storage

Store at 2-8°C,Argon charged

Shipped In

Wet ice

Übersicht

Prexasertib dimesylate (LY2606368 dimesylate) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K i of 0.9 nM and an IC 50 of <1 nM. Prexasertib dimesylate inhibits CHK2 (IC 50 =8 nM) and RSK1 (IC 50 =9 nM). Prexasertib dimesylate causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis . Prexasertib dimesylate shows potent anti-tumor activity

In Vitro

Prexasertib dimesylate (LY2606368 dimesylate) inhibits MELK (IC 50 =38 nM), SIK (IC 50 =42 nM), BRSK2 (IC 50 =48 nM), ARK5 (IC 50 =64 nM). Prexasertib dimesylate requires CDC25A and CDK2 to cause DNA damage. Prexasertib dimesylate (33, 100 nM; for 7 hours) results in DNA damage during S-phase in HeLa cells. Prexasertib dimesylate (8-250 nM; pre-treated for 15 minutes) inhibits CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) in HT-29 cells. Prexasertib dimesylate (4 nM; 24 hours) results in a large shift in cell-cycle populations from G1 and G2-M to S-phase with an accompanied induction of H2AX phosphorylation in U-2 OS cells. Prexasertib dimesylate (33 nM; for 12 hours) causes chromosomal fragmentation in HeLa cells. Prexasertib dimesylate (100 nM; 0.5 to 9 hours) induces replication stress and depletes the pool of available RPA2 for binding to DNA. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Cycle AnalysisCell Line: HeLa cells Concentration: 33, 100 nM Incubation Time: For 7 hours Result: Had an IC 50 of 37 nM and resulted in the G2-M population received DNA damage during S-phase but continued to progress through the cell cycle into an early mitosis. Western Blot AnalysisCell Line: HT-29 cells Concentration: 8, 16, 31, 63, 125, 250 nM Incubation Time: Pre-treated for 15 minutes Result: Inhibited CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) (IC 50 of less than 31 nM) in HT-29 cells.

In Vivo

Prexasertib dimesylate (LY2606368 dimesylate; 1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) causes growth inhibition in tumor xenografts . Prexasertib dimesylate (15 mg/kg; SC) causes CHK1 inhibition in the blood and the phosphorylation of both H2AX (S139) and RPA2 (S4/S8) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells Dosage: 1, 3.3, or 10 mg/kg Administration: SC; twice daily for 3 days, rest 4 days; for three cycles Result: Caused statistically significant tumor growth inhibition (up to 72.3%). Animal Model: Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells Dosage: 15 mg/kg (Pharmacokinetic Analysis) Administration: SC (200 μL) Result: CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures. Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage.

Form:Solid

IC50& Target:Chk1 0.9 nM (Ki) Chk1 <1 nM (IC 50 ) Chk2 8 nM (IC 50 )

Specifications

Synonyme

5-((5-(2-(3-Aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile dimethanesulfonate | SCHEMBL20591301 | CS-0130202

Spezifikationen & Reinheit

Moligand™, ≥99%

Biochemische und physiologische Mechanismen

Prexasertib dimesylate (LY2606368 dimesylate) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K i of 0.9 nM and an IC 50 of <1 nM. Prexasertib dimesylate inhibits CHK2 (IC 50 =8 nM) and RSK1 (IC 50 =9 nM). Pre

Storage

Store at 2-8°C,Argon charged

Verschickt in

Wet ice

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Note

Moligand™

Reinheit

≥99%

Namen und Kennungen

Pubchem Sid

528766800

Kanonisches Lächeln

COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N.CS(=O)(=O)O.CS(=O)(=O)O

IUPAC Name

5-[[5-[2-(3-aminopropoxy)-6-methoxyphenyl]-1H-pyrazol-3-yl]amino]pyrazine-2-carbonitrile;methanesulfonic acid

InChIKey

HXYBEKZGRNUTBN-UHFFFAOYSA-N

INCHI

1S/C18H19N7O2.2CH4O3S/c1-26-14-4-2-5-15(27-7-3-6-19)18(14)13-8-16(25-24-13)23-17-11-21-12(9-20)10-22-17;2*1-5(2,3)4/h2,4-5,8,10-11H,3,6-7,19H2,1H3,(H2,22,23,24,25);2*1H3,(H,2,3,4)

PubChem CID

137364590

Molekulargewicht

557.60

Chemische und physikalische Eigenschaften

• Löslichkeit: DMSO : 100 mg/mL (179.34 mM; Need ultrasonic) H2O : 50 mg/mL (89.67 mM; Need ultrasonic)