Zunsemetinib
new
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 207172

CAS#: 1640282-42-3 (P-atropisomer)

Description: Zunsemetinib, also known as ATI-450 and CDD450, is a potent MK2 Inhibitor. ATI-450 binds with high affinity to the interface of the p38MAPK-MK2 complex and selectively inhibits p38MAPK-catalysed phosphorylation of MK2 which stabilises the inactive conformation of MK2, and subsequently reduces inflammatory cytokine levels. ATI-450 specifically blocks the downstream MK2-mediated inflammatory drive on the p38 pathway and may therefore avoid the tachyphylaxis associated with p38 inhibitors. Note CAS#1640282-42-3 is the active P-atropisomer. CAS# 1640282-44-5 is the inactive M-astropisomer.


Chemical Structure

img
Zunsemetinib
CAS# 1640282-42-3 (P-atropisomer)

Theoretical Analysis

MedKoo Cat#: 207172
Name: Zunsemetinib
CAS#: 1640282-42-3 (P-atropisomer)
Chemical Formula: C25H22ClF2N5O3
Exact Mass: 513.1379
Molecular Weight: 513.9298
Elemental Analysis: C, 58.43; H, 4.31; Cl, 6.90; F, 7.39; N, 13.63; O, 9.34

Price and Availability

Size Price Availability Quantity
0.5mg USD 150.0 Ready to ship
1.0mg USD 250.0 Ready to Ship
5.0mg USD 750.0 Ready to Ship
10.0mg USD 1250.0 Ready to ship
25.0mg USD 2650.0 Ready to ship
Bulk inquiry

Related CAS #: 1639791-42-6 (racemate)   1640282-42-3 (P-atropisomer)   1640282-44-5 (M-atropisomer)  

Synonym: Zunsemetinib; (P)-ATI-450; ATI-450 P atropisomer; ATI-450; ATI450; ATI 450; CDD-450; CDD 450; CDD450;

IUPAC/Chemical Name: (2'S)-3-Chloro-4-[(3,5-difluoro-2-pyridinyl)methoxy]-2'-[2-(1-hydroxy-1-methylethyl)-4-pyrimidinyl]-5',6-dimethyl[1(2H),4'-bipyridin]-2-one

InChi Key: FQPQMJULRZINPV-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H22ClF2N5O3/c1-13-10-30-18(17-5-6-29-24(32-17)25(3,4)35)9-20(13)33-14(2)7-21(22(26)23(33)34)36-12-19-16(28)8-15(27)11-31-19/h5-11,35H,12H2,1-4H3

SMILES Code: O=C1C(Cl)=C(OCC2=NC=C(F)C=C2F)C=C(C)N1C3=CC(C4=NC(C(C)(O)C)=NC=C4)=NC=C3C

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: To be determined

Shelf Life: >2 years if stored properly

Drug Formulation: To be determined

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Zunsemetinib (CDD-450) is an orally active and selective p38α mitogen-activated protein kinase-activated protein kinase 2 (MK2) pathway inhibitor. Zunsemetinib can be used for the research of immuno-inflammatory diseases.
In vitro activity: This study found that both PF3644022 and ATI-450 robustly suppressed SN-38-induced p-Beclin1 (S90) and LC3-II (Fig. 4F). ATI-450 also suppressed SN-38-induced p-ULK1 and p-AMPKα, further supporting MK2 as an activator of protective autophagy through Beclin1 under genotoxic stress. Reference: Sci Transl Med. 2021 Dec;13(622):eabb5445. https://pubmed.ncbi.nlm.nih.gov/34851698/
In vivo activity: Consistent with a resolution of inflammation, this study found that ATI450 treatment led to a significant decrease in the number of colonic T cells in animals that had inflammation (Fig. 3g). Altogether, these results demonstrate that inhibition of the MK2 pathway with ATI450 suppresses active colitis in the TCT model. Reference: Integr Biol (Camb). 2019 Nov 26;11(7):301-314. https://pubmed.ncbi.nlm.nih.gov/31617572/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 194.58

Preparing Stock Solutions

The following data is based on the product molecular weight 513.9298 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Grierson PM, Dodhiawala PB, Cheng Y, Chen TH, Khawar IA, Wei Q, Zhang D, Li L, Herndon J, Monahan JB, Ruzinova MB, Lim KH. The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress. Sci Transl Med. 2021 Dec;13(622):eabb5445. doi: 10.1126/scitranslmed.abb5445. Epub 2021 Dec 1. PMID: 34851698; PMCID: PMC9475471. 3. Strasser SD, Ghazi PC, Starchenko A, Boukhali M, Edwards A, Suarez-Lopez L, Lyons J, Changelian PS, Monahan JB, Jacobsen J, Brubaker DK, Joughin BA, Yaffe MB, Haas W, Lauffenburger DA, Haigis KM. Substrate-based kinase activity inference identifies MK2 as driver of colitis. Integr Biol (Camb). 2019 Nov 26;11(7):301-314. doi: 10.1093/intbio/zyz025. PMID: 31617572; PMCID: PMC7208439. 4. Wang C, Hockerman S, Jacobsen EJ, Alippe Y, Selness SR, Hope HR, Hirsch JL, Mnich SJ, Saabye MJ, Hood WF, Bonar SL, Abu-Amer Y, Haimovich A, Hoffman HM, Monahan JB, Mbalaviele G. Selective inhibition of the p38α MAPK-MK2 axis inhibits inflammatory cues including inflammasome priming signals. J Exp Med. 2018 May 7;215(5):1315-1325. doi: 10.1084/jem.20172063. Epub 2018 Mar 16. PMID: 29549113; PMCID: PMC5940269.
In vitro protocol: 1. Grierson PM, Dodhiawala PB, Cheng Y, Chen TH, Khawar IA, Wei Q, Zhang D, Li L, Herndon J, Monahan JB, Ruzinova MB, Lim KH. The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress. Sci Transl Med. 2021 Dec;13(622):eabb5445. doi: 10.1126/scitranslmed.abb5445. Epub 2021 Dec 1. PMID: 34851698; PMCID: PMC9475471.
In vivo protocol: 1. Strasser SD, Ghazi PC, Starchenko A, Boukhali M, Edwards A, Suarez-Lopez L, Lyons J, Changelian PS, Monahan JB, Jacobsen J, Brubaker DK, Joughin BA, Yaffe MB, Haas W, Lauffenburger DA, Haigis KM. Substrate-based kinase activity inference identifies MK2 as driver of colitis. Integr Biol (Camb). 2019 Nov 26;11(7):301-314. doi: 10.1093/intbio/zyz025. PMID: 31617572; PMCID: PMC7208439. 2. Wang C, Hockerman S, Jacobsen EJ, Alippe Y, Selness SR, Hope HR, Hirsch JL, Mnich SJ, Saabye MJ, Hood WF, Bonar SL, Abu-Amer Y, Haimovich A, Hoffman HM, Monahan JB, Mbalaviele G. Selective inhibition of the p38α MAPK-MK2 axis inhibits inflammatory cues including inflammasome priming signals. J Exp Med. 2018 May 7;215(5):1315-1325. doi: 10.1084/jem.20172063. Epub 2018 Mar 16. PMID: 29549113; PMCID: PMC5940269.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Grierson PM, Dodhiawala PB, Cheng Y, Chen TH, Khawar IA, Wei Q, Zhang D, Li L, Herndon J, Monahan JB, Ruzinova MB, Lim KH. The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress. Sci Transl Med. 2021 Dec;13(622):eabb5445. doi: 10.1126/scitranslmed.abb5445. Epub 2021 Dec 1. PMID: 34851698; PMCID: PMC9475471.

2: Gordon D, Hellriegel ET, Hope HR, Burt D, Monahan JB. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the MK2 Inhibitor ATI-450 in Healthy Subjects: A Placebo-Controlled, Randomized Phase 1 Study. Clin Pharmacol. 2021 Jun 10;13:123-134. doi: 10.2147/CPAA.S305308. PMID: 34140814; PMCID: PMC8203602.