MA203
MA203 is a selective CHK1 PROTAC degrader. MA203 targets activated CHK1 for degradation by recruiting the CRBN E3 ubiquitin ligase, thereby completely abolishing both its catalytic and non-catalytic functions and ultimately triggering DNA replication catastrophe and apoptosis. MA203 can be used in research related to pancreatic ductal adenocarcinoma, colorectal cancer, and acute lymphoblastic leukemia.
(Pink: Chk1 ligand (HY-179158); Blue: Cereblon ligand (HY-41547); Black: linker (HY-22391)).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Formule: C38H45N9O8
- Masse moléculaire:755.82
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
Chk1 |
Bax |
Bcl-xL |
In Vitro
MA203 (2 μM; 3-24 h) hydrochloride, in combination with HU (HY-B0313), significantly reduces CHK1 protein levels and upregulates γH2AX phosphorylation levels in MIA PaCa-2, MOLT-4, and HCT116 cells in a time- and concentration-dependent manner[1].
MA203 (2 μM; 24 h) hydrochloride, with or without HU treatment, degrades CHK1 in MOLM-13 and RS4-11 cells[1].
MA203 (0.5-10 μM; 24 h) hydrochloride, in combination with HU treatment, dose-dependently upregulates γH2AX phosphorylation and p-ATM (S1981) levels, significantly increases γH2AX foci, and exacerbates DNA single-strand breaks in MIA PaCa-2 and MOLT-4 cells[1].
MA203 (2 μM; 24 h) hydrochloride, in combination with 1 mM HU treatment, upregulates γH2AX phosphorylation levels in MOLT-4 and HCT116 cells[1].
MA203 (1-5 μM; 24 h) hydrochloride, in combination with Ara-C (HY-13605) treatment, synergistically enhances Ara-C cytotoxicity in MOLT-4 cells, does not affect cell viability and activation status in activated T and B cells, and does not significantly impair cell survival in mouse hematopoietic stem cells (HSCs)[1].
MA203 (2 μM; 7 days) hydrochloride inhibits cell proliferation in MOLT-4 cells but exerts no effect on RPE1 cells[1].
MA203 (1-10 μM; 48 h) hydrochloride, in combination with HU treatment, induces apoptosis in MIA PaCa-2, HCT116, MOLT-4, and MOLM-13 cells, but does not affect cell viability in RPE1, HS-5, and PBMCs[1].
MA203 (2 μM; 16-48 h) hydrochloride, in combination with 1 mM HU treatment, downregulates the protein expression of TCF1/7, CDCA7, RRM2, ORC1, WRN, and claspin, reduces p-CHK1 (S296) levels, promotes G1 phase arrest, increases the proportion of sub-G1 cells, upregulates BAX, BIM, and NOXA while downregulating BCL-XL and XIAP, significantly increases the loss of mitochondrial membrane potential, and enhances the cleavage of caspase-8, caspase-3, and PARP1 in MIA PaCa-2 cells[1].
MA203 hydrochloride potently binds to purified human CHK1 protein, with a binding rate of 97% at 1.0 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MIA PaCa-2, MOLT-4
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Concentration:2 μM
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Incubation Time:3, 6, 10, 16, 24 h
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Result:Degraded CHK1 in combination with HU, without affecting off-target proteins such as CHK2 and GSPT.
Decreased CHK1 levels and altered its phosphorylation status in a time-dependent manner.
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Cell Line:MIA PaCa-2
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Concentration:2 μM
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Incubation Time:24 h
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Result:Significantly increased the accumulation of γH2AX foci in combination with HU.
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Cell Line:MIA PaCa-2, HCT116, MOLT-4, MOLM-13
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Concentration:2 μM
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Incubation Time:24 h or 48 h
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Result:Significantly induced early and late apoptosis in combination with HU.
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Cell Line:MIA PaCa-2
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Concentration:2 μM
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Incubation Time:24 h and 48 h
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Result:Promoted G1 phase arrest and increased the proportion of cells in the subG1 phase in combination with HU.
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Cell Line:MOLT-4 and RPE1
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Concentration:2 μM
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Incubation Time:7 days
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Result:Inhibited the proliferation of leukemia cells, but did not affect normal cells.
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Cell Line:MIA PaCa-2
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Concentration:2 μM
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Incubation Time:24 h and 48 h
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Result:Downregulated key proteins involved in DNA repair and replication (such as WRN, TCF1/7) and modulated the expression of apoptosis-related BCL2 family proteins.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:wild-type AB strain (2 days post-fertilization)[2]
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Dosage:12 μM
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Administration:immersion; continuous; 48 h
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Result:Inhibited the MOLT-4 tumor burden xenografted in zebrafish.
Chemical Information
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Masse moléculaire 755.82
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Formule C38H45N9O8
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SMILES
O=C1CCC(N2C(C(C=CC=C3NCCCCCCCNC(C4=CC(OC[C@H]5OCCNC5)=C(NC(NC6=CN=C(C)C=N6)=O)C=C4)=O)=C3C2=O)=O)C(N1)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MA203 Related Classifications
HY-179157 Related Classifications
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