MS67 - ≥98% , CAS No.2407452-77-9

CAS: 2407452-77-9 Cat. No.: M646896 Molecular Weight: 1030.14 PubChem CID: 153379992

GRADE & PURITY ≥98%

Storage

Store at -20°C,Desiccated

Shipped In

Ice chest + Ice pads

Application

PROTAC

Overview

MS67 is a potent and selective WD40 repeat domain protein 5 (WDR5) degrader with a K d of 63 nM. MS67 is inactive against other protein methyltransferases, kinases, GPCRs, ion channels, and transporters. MS67 shows potent acticancer effects

In Vitro

MS67 (0.001-1 μM) induces WDR5 degradation at a concentration as low as 1 nM. MS67 induces WDR5 depletion much more effectively in all six mixed lineage leukemia (MLL)-r acute myeloid leukemia (AML) and four pancreatic ductal adenocarcinoma (PDAC) cell lines without a hook effect and in a concentration-dependent manner in PDAC cells. MS67 decreases H3K4me2/3 in both MV4;11 and MIA PaCa-2 cells, whereas other examined histone methylation marks such as H3K9me3, H3K27me3, and H3K36me3 are not affected . MS67 is effective in suppressing both WDR5-related gene expression programs and WDR5/MLL-induced H3K4 methylations on chromatin. The GI 50 values of MS67 in the two most sensitive AML lines, MV4;11 and EOL-1, are 15 nM and 38 nM, respectively. MLL-r acute leukemia cell lines including MV4;11, EOL-1, MOLM13, KOPN8, RS4;11, and THP-1 are sensitive to MS67, whereas leukemia cell lines that did not harbor MLL-r (including K562, HL60, and a murine AML line transformed by Hoxa9 plus Meis1) are insensitive to MS67. .\nMS67 binds to VCB (VHL-Elongin C-Elongin B ternary complex), with a K d of 140 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: MV4;11 cells Concentration: 0.001 μM, 0.005 μM, 0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM Incubation Time: 18 hours Result: Induced WDR5 degradation at a concentration as low as 1 nM with DC 50 of 3.7 nM.

In Vivo

MS67 (75 mg/kg; i.p.; twice daily; 5 days a week; for 20 days) significantly inhibits tumor growth in vivo and prolongs survival of the treated mice . After a single intraperitoneal (i.p.) injection of MS67 at a dose of 75 mg/kg, the Cmax reached at about 4.2 μM, and the concentration of MS67 retained above 0.5 μM over 12 hours . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: MV4;11 MLL-r AML xenograft mouse Dosage: 75 mg/kg Administration: i.p.; twice daily; 5 days a week; for 20 days Result: Inhibited tumor growth in vivo.

Form:Solid

IC50& Target:VHL WDR5 63 nM (Kd)

Specifications

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

MS67 is a potent and selective WD40 repeat domain protein 5 (WDR5) degrader with a K d of 63 nM. MS67 is inactive against other protein methyltransferases, kinases, GPCRs, ion channels, and transporters. MS67 shows potent acticancer effects.

Storage

Store at -20°C, Desiccated

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥98%

Names and Identifiers

• Canonical Smiles: CC1CN(CC(N1C)C)C2=C(C=C(C=C2)C3=C(C=CC(=C3)C(=O)NCC(=O)NC(C(=O)N4CC(CC4C(=O)NC(C)C5=CC=C(C=C5)C6=C(N=CS6)C)O)C(C)(C)C)F)NC(=O)C7=CNC(=O)C=C7C(F)(F)F
• IUPAC Name: N-[5-[2-fluoro-5-[[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethyl]carbamoyl]phenyl]-2-[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]phenyl]-6-oxo-4-(trifluoromethyl)-1H-pyridine-3-carboxamide
• InChIKey: HBHSDSLZXDASLT-FLKKWHKHSA-N
• INCHI: 1S/C52H59F4N9O7S/c1-27-23-64(24-28(2)63(27)8)41-16-14-33(18-40(41)61-48(70)37-21-57-43(67)20-38(37)52(54,55)56)36-17-34(13-15-39(36)53)47(69)58-22-44(68)62-46(51(5,6)7)50(72)65-25-35(66)19-42(65)49(71)60-29(3)31-9-11-32(12-10-31)45-30(4)59-26-73-45/h9-18,20-21,26-29,35,42,46,66H,19,22-25H2,1-8H3,(H,57,67)(H,58,69)(H,60,71)(H,61,70)(H,62,68)/t27-,28+,29-,35+,42-,46+/m0/s1
• PubChem CID: 153379992
• Molecular Weight: 1030.14

Chemical and Physical Properties

• Solubility: DMSO : 100 mg/mL (97.07 mM; ultrasonic and warming and heat to 60°C)