Cat. No.: HY-P12219

COG449

Name: COG449
Brand: MedChemExpress
SKU: HY-P12219
Availability: PreOrder

(Synonyms: OP449)

COG449 (OP449) is a cell-penetrating peptide that binds to SET, prevents the formation of the SET-PP2A complex, and restores PP2A phosphatase activity. COG449 decreases the phosphorylation levels of AKT³⁰⁸, ERK1/2, NFkB p65, and c-MYC S62, and reduces c-MYC stability and target gene expression. COG449 induces apoptosis, autophagy, and histone H3 hyperacetylation, and decreases the levels of SET, CIP2A, SETBP1, and Mcl-1. COG449 reduces cancer cell viability and decreases tumor mass in xenograft models. COG449 can be used for research on various cancers such as oral squamous cell carcinoma, T-cell acute lymphoblastic leukemia, B-CLL, non-Hodgkin lymphoma, and breast cancer.

For research use only. We do not sell to patients.

Formula: C₄₁₈H₇₁₂N₁₄₆O₈₂S₄
Molecular Weight:9223.31

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Please store the product under the recommended conditions in the Certificate of Analysis.

COG449 Chemical Structure

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[2]

ERK1

ERK2

All Akt Isoforms :

All ERK Isoforms :

All NF-κB Isoforms :

All Histone Acetyltransferase Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
WSU-HN13	IC50	5.94 μM	Reduction in cell viability of human HN13 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay. Reduction in cell viability of human HN13 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay.	32569675
HN12	IC50	5.11 μM	Reduction in cell viability of human HN12 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay. Reduction in cell viability of human HN12 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay.	32569675
HN-6	IC50	9.17 μM	Reduction in cell viability of human HN6 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay. Reduction in cell viability of human HN6 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay.	32569675
CAL-27	IC50	8.86 μM	Reduction in cell viability of human Cal27 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay. Reduction in cell viability of human Cal27 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay.	32569675
SCC-9	IC50	6.26 μM	Reduction in cell viability of human SCC9 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay. Reduction in cell viability of human SCC9 head and neck squamous cell carcinoma cells assessed after incubation for 72 hrs by resazurin assay.	32569675
Jurkat	IC50	1.25 μM	Inhibition of cell viability in human JURKAT T-ALL cells assessed by MTS assay after 72 hrs incubation. Inhibition of cell viability in human JURKAT T-ALL cells assessed by MTS assay after 72 hrs incubation.	27705940
LOUCY	IC50	1.25 μM	Inhibition of cell viability in human LOUCY T-ALL cells assessed by MTS assay after 72 hrs incubation. Inhibition of cell viability in human LOUCY T-ALL cells assessed by MTS assay after 72 hrs incubation.	27705940
RPMI 8402	IC50	1.25 μM	Inhibition of cell viability in human RPMI-8402 T-ALL cells assessed by MTS assay after 72 hrs incubation. Inhibition of cell viability in human RPMI-8402 T-ALL cells assessed by MTS assay after 72 hrs incubation.	27705940
MOLT-4	IC50	1.25 μM	Inhibition of cell viability in human MOLT-4 T-ALL cells assessed by MTS assay after 72 hrs incubation. Inhibition of cell viability in human MOLT-4 T-ALL cells assessed by MTS assay after 72 hrs incubation.	27705940
K562	IC50	2.5 μM	Cytotoxicity against human K562 CML cells assessed as reduction in proliferation and increased apoptosis. Cytotoxicity against human K562 CML cells assessed as reduction in proliferation and increased apoptosis.	blood.V118.21.3757.3757
BaF3	IC50	0.89 μM	Inhibition of proliferation of murine Ba/F3 cells expressing wild-type BCR-ABL1 incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay. Inhibition of proliferation of murine Ba/F3 cells expressing wild-type BCR-ABL1 incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay.	24436473
BaF3	IC50	1.62 μM	Inhibition of proliferation of murine Ba/F3 cells expressing imatinib-insensitive BCR-ABL1T315I point mutant incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay. Inhibition of proliferation of murine Ba/F3 cells expressing imatinib-insensitive BCR-ABL1T315I point mutant incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay.	24436473
BaF3	IC50	1.97 μM	Inhibition of proliferation of murine Ba/F3 cells expressing BCR-ABL1E255V/T315I compound mutant incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay. Inhibition of proliferation of murine Ba/F3 cells expressing BCR-ABL1E255V/T315I compound mutant incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay.	24436473
K562	IC50	0.60 μM	Inhibition of proliferation of human CML K562 cells incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay. Inhibition of proliferation of human CML K562 cells incubated for 72 hrs by Cell Titer 96 Aqueous One solution assay.	24436473
MOLM-14	IC50	0.59 μM	Inhibition of proliferation of human AML MOLM-14 cells harboring FLT3-ITD incubated for 72 hrs by cell viability assay. Inhibition of proliferation of human AML MOLM-14 cells harboring FLT3-ITD incubated for 72 hrs by cell viability assay.	24436473
GDM-1	IC50	0.82 μM	Inhibition of proliferation of human AML GDM-1 cells with CSF1R overexpression incubated for 72 hrs by cell viability assay. Inhibition of proliferation of human AML GDM-1 cells with CSF1R overexpression incubated for 72 hrs by cell viability assay.	24436473
HL-60	IC50	0.94 μM	Inhibition of proliferation of human AML HL-60 cells harboring NRASQ61L incubated for 72 hrs by cell viability assay. Inhibition of proliferation of human AML HL-60 cells harboring NRASQ61L incubated for 72 hrs by cell viability assay.	24436473
CMK	IC50	1.73 μM	Inhibition of proliferation of human AML CMK cells harboring JAK3A572V incubated for 72 hrs by cell viability assay. Inhibition of proliferation of human AML CMK cells harboring JAK3A572V incubated for 72 hrs by cell viability assay.	24436473
UT7	IC50	1.78 μM	Inhibition of proliferation of human AML UT7 cells incubated for 72 hrs by cell viability assay. Inhibition of proliferation of human AML UT7 cells incubated for 72 hrs by cell viability assay.	24436473

In Vitro

COG449 (0-7.0 μM; 72 h) reduces cell viability in HN13, HN12, HN6, Cal27, and SCC9 OSCC cell lines with IC₅₀ values of 5.94 μM, 5.11 μM, 9.17 μM, 8.86 μM, and 6.26 μM, respectively, and reduces viability in NOK-SI and NOK-SI/SET cells with IC₅₀ values of 8.95 μM and 9.16 μM, respectively^[1].
COG449 (72 h) inhibits the growth of NOTCH-dependent and -independent T-ALL cells with an IC₅₀ of 1.25 μM at 72 h^[2].
COG449 (1 μM) reduces total c-MYC and phospho-S62 c-MYC levels in RPMI-8402 and JURKAT T-ALL cells^[2].
COG449 (1 μM) reduces the phosphorylation of ERK1/2 and AKT in RPMI-8402 and JURKAT cells^[2].
COG449 (1 μM) negatively affects c-MYC transcriptional activity and reduces the levels of SET, CIP2A, and SETBP1 in T-ALL cells^[2].
COG449 (1 μM) reduces tyrosine phosphorylation of PP2Ac in T-ALL cells^[2].
COG449 (24 h) induces dose-dependent cytotoxicity in breast cancer cell lines and immortalized MCF10A cells^[4].
COG449 significantly reduces the anchorage-independent growth of MDA-MB-231, HCC38, SKBR3, MDA-MB-436, and MDA-MB-468 breast cancer cells^[4].
COG449 (1-2 μM; 4 h) reduces pS62-MYC levels in MDA-MB-231, HCC38, MDA-MB-436, and MDA-MB-468 breast cancer cells^[4].
COG449 (1 µM) increases PP2A activity by 45% in K562 and 32Dp210 CML cells^[5].
COG449 is cytotoxic to K562 and LAMA CML cells, with IC₅₀ values of 2.5 µM and 1.25 µM, respectively^[5].
COG449 exhibits selective cytotoxicity against BCR-ABL-positive CML cells^[5].
COG449 is cytotoxic to the TKI-resistant 32Dp210^T315I mutant cell line, with an IC₅₀ of 2.5 µM^[5].
COG449 (2.5-5 µM) inhibits colony formation in primary CML CD34⁺ cells without affecting normal human CD34⁺ cells^[5].
COG449 (72 h) selectively inhibits the growth of Ba/F3 cells expressing wild-type and mutant BCR-ABL1, as well as K562 and LAMA CML cell lines, with IC₅₀ values ranging from 0.60 to 1.97 μM, while showing no effect on parental Ba/F3 cells^[6].
COG449 (2.5 μM) effectively inhibits the growth of primary CML blast crisis cells harboring wild-type BCR-ABL1 (90% inhibition) and BCR-ABL1^T315I (35% inhibition)^[6].
COG449 (10-20 μM; 2-6 h) alters multiple SET targets in HN12 and SCC9 cells and activates apoptosis and autophagy markers^[1].
COG449 (10-20 μM; 2-6 h) modulates SET targets in NOK-SI and NOK-SI/SET cells and induces apoptosis and autophagy markers, with dose-dependent effects on histone H3 acetylation^[1].
COG449 (0.62-1.25 μM) increases PP2A activity in a dose-dependent manner in JURKAT, LOUCY, RPMI-8402, and MOLT-4 T-ALL cell lines^[2].
COG449 (1 μM) reduces the binding of SET to PP2Ac in T-ALL cell lines^[2].
COG449 (1 μM) reduces the binding of phospho-S62 c-Myc to PP2Ac in T-ALL cells^[2].
COG449 is a SET-targeting agent that activates PP2A and reduces Mcl-1 levels by disrupting the SET-PP2A complex, and has shown activity in B-CLL and non-Hodgkin lymphoma^[3].
COG449 (48 h) induces apoptosis in mouse and human CML cell lines^[6].
COG449 (6 h) induces apoptosis in MDA-MB-231 breast cancer cells^[4].
COG449 (6 h) reduces CIP2a levels in CD34⁺ CML and K562 cells and inhibits BCR-ABL downstream signaling^[5].
COG449 (24 h) attenuates BCR-ABL1 kinase signaling and leads to BCR-ABL1 degradation in K562 cells^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[1]

Cell Line:

HN13, HN12, HN6, Cal27, SCC9
Concentration:

0, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 7.0 μM
Incubation Time:

72 h
Result:

Decreased cell viability in HN13, HN12, HN6, Cal27, and SCC9 cell lines in a dose-dependent manner.
Achieved IC50 values of 5.94 μM for HN13, 5.11 μM for HN12, 9.17 μM for HN6, 8.86 μM for Cal27, and 6.26 μM for SCC9.

Cell Viability Assay^[1]

Cell Line:

NOK-SI, NOK-SI/SET
Concentration:

0, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 7.0 μM
Incubation Time:

72 h
Result:

Decreased cell viability in NOK-SI and NOK-SI/SET cells.
Achieved IC50 values of 8.95 μM for NOK-SI and 9.16 μM for NOK-SI/SET.

Western Blot Analysis^[1]

Cell Line:

HN12, SCC9
Concentration:

10, 20 μM
Incubation Time:

2, 4, 6 h
Result:

Induced a marked increase of p21 and reduction of pAKT308, pNFκB, and NFκB levels in HN12 cells.
Showed reduction of pNFκB, NFκB, and AKT, a decrease in ERK1/2 levels, and an increase of acetyl histone H3 levels in SCC9 cells.
Decreased PARP (full length) levels and increased LC3 lipidation (LC3-II) in both HN12 and SCC9 cells.

Western Blot Analysis^[1]

Cell Line:

NOK-SI, NOK-SI/SET
Concentration:

10, 20 μM
Incubation Time:

2, 4, 6 h
Result:

Decreased the levels of pNFκB, NFκB, pAKT308, SET, and p53, and increased the levels of pERK and acetyl histone H3.
Increased the levels of acetyl-H3 histones at 10 μM, while 20 μM promoted a drastic reduction in these levels.
Reduced PARP (full length) in both cell lines.
Confirmed increased LC3 lipidation (LC3-II).
Observed an increase of LC3-II/LC3-I ratio in NOK-SI/SET cells.

Western Blot Analysis^[4]

Cell Line:

MDA-MB-231, HCC38, MDA-MB-436, and MDA-MB-468 cells
Concentration:

1, 2 μM (MDA-MB-231); 0.5, 1 μM (HCC38); 1, 2 μM (MDA-MB-436); 1, 2 μM (MDA-MB-468)
Incubation Time:

4 h
Result:

Decreased pS62-MYC/GAPDH ratios from 1.0 to 0.72 (1 μM) and 0.50 (2 μM) in MDA-MB-231; from 1.0 to 0.64 (0.5 μM) and 0.54 (1 μM) in HCC38; from 1.0 to 0.70 (1 μM) and 0.42 (2 μM) in MDA-MB-436; from 1.0 to 0.60 (1 μM) and 0.39 (2 μM) in MDA-MB-468.
MYC/GAPDH ratios were 1.0, 1.13 (1 μM), and 1.08 (2 μM) in MDA-MB-231; 1.0, 1.05 (0.5 μM), and 1.17 (1 μM) in HCC38; 1.0, 0.78 (1 μM), and 0.56 (2 μM) in MDA-MB-436; 1.0, 0.68 (1 μM), and 0.38 (2 μM) in MDA-MB-468.

In Vivo

COG449 (5 mg/kg; i.p.; three times per week; up to 40 days) reduces mammary tumor growth in mice, which is associated with increased apoptosis, decreased proliferation, and increased PP2A activity in tumors^[4].
COG449 (5 mg/kg; i.p.; once every 3 days) significantly inhibits AML tumor growth in mice, reducing tumor burden by more than 2-fold compared with the vehicle control group^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

NOD/SCID/γ-chain null (NSG) (female, orthotopic xenografts of MDA-MB-231, MDA-MB-436, and MDA-MB-468 cells into the fourth mammary gland)^[4]
Dosage:

5 mg/kg
Administration:

i.p.; three times per week; up to 40 days
Result:

Slowed tumor growth in MDA-MB-231, MDA-MB-436, and MDA-MB-468 xenografts compared with controls.
Increased the number of apoptotic cells in MDA-MB-231 tumors as measured by TUNEL assay.
Decreased the number of proliferating cells in MDA-MB-231 tumors as measured by Ki67 staining.
Was specifically detected in the tumors of treated mice.
Significantly increased PP2A activity in treated tumors compared with PBS-treated tumors.

Animal Model:

RAG2−/− γc−/− mice (20 g)^[6]
Dosage:

5 mg/kg
Administration:

i.p.; every 3 days; starting 7 days post-implantation
Result:

Inhibited tumor growth measured over time.
Reduced tumor burden by more than 2-fold compared with vehicle-treated controls, with final tumor mass of 0.45 g versus 1.14 g for vehicle.

Related Protocols :

Chemical Information

Molecular Weight 9223.31
Formula C₄₁₈H₇₁₂N₁₄₆O₈₂S₄
SMILES

O=C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CCC(N)=O)C(N[C@@H]([C@@H](C)CC)C(N[C@@H](CCCCN)C(N[C@@H]([C@@H](C)CC)C(N[C@@H](CC1=CNC2=CC=CC=C12)C(N[C@@H](CC3=CC=CC=C3)C(N[C@@H](CCC(N)=O)C(N[C@@H](CC(N)=O)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CCSC)C(N[C@@H](CCCCN)C(N[C@@H](CC4=CNC5=CC=CC=C45)C(N[C@@H](CCCCN)C(N[C@@H](CCCCN)C(N[C@@H](CSC(C6=O)CC(N6CCN7C(CC(SC[C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC(C)=O)CCCNC(N)=N)=O)CCC(N)=O)=O)[C@H](CC)C)=O)CCCCN)=O)[C@H](CC)C)=O)CC8=CNC9=CC=CC=C98)=O)CC%10=CC=CC=C%10)=O)CCC(N)=O)=O)CC(N)=O)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CCSC)=O)CCCCN)=O)CC%11=CNC%12=CC=CC=C%12%11)=O)CCCCN)=O)CCCCN)=O)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N)=O)CC(C)C)=O)CC(C)C)=O)CCCNC(N)=N)=O)CCCCN)=O)CCCNC(N)=N)=O)CC(C)C)=O)CCCCN)=O)CCCNC(N)=N)=O)CC(C)C)=O)CC%13=CNC=N%13)=O)CO)=O)C)=O)CC(C)C)=O)CCCNC(N)=N)=O)C(C)C)=O)CCCNC(N)=N)=O)CC(C)C)=O)C7=O)=O)=O)C(N[C@@H](CC(C)C)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](C(C)C)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CC(C)C)C(N[C@@H](C)C(N[C@@H](CO)C(N[C@@H](CC%14=CNC=N%14)C(N[C@@H](CC(C)C)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CCCCN)C(N[C@@H](CC(C)C)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CCCCN)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CC(C)C)C(N[C@@H](CC(C)C)C(N)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)C
Synonyms

OP449
Sequence

Ac-Arg-Gln-Ile-Lys-Ile-Trp-Phe-Gln-Asn-Arg-Arg-Met-Lys-Trp-Lys-Lys-Cys-Leu-Arg-Val-Arg-Leu-Ala-Ser-His-Leu-Arg-Lys-Leu-Arg-Lys-Arg-Leu-Leu-NH2 (BMOE-linked Cys17 dimer)
Sequence Shortening

Ac-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRLL-NH2 (BMOE-linked Cys17 dimer)
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Goto RN, et al. Synergic effect of OP449 and FTY720 on oral squamous cell carcinoma. European journal of pharmacology. 2020 Sep 05;882:173268.

[2]. Richard NP, et al. Combined targeting of SET and tyrosine kinases provides an effective therapeutic approach in human T-cell acute lymphoblastic leukemia. Oncotarget. 2016 Dec 20;7(51):84214-84227.

[3]. Maier J, et al. CLL to Richter syndrome: Integrating network strategies with experiments elucidating disease drivers and personalized therapies. Science advances. 2025 Sep 12;11(37):eadu7705.

[4]. Janghorban M. Targeting c-MYC by antagonizing PP2A inhibitors in breast cancer. Proceedings of the National Academy of Sciences. 2014 Jun 24;111(25):9157-62.

[5]. Agarwal A, et al. A novel SET antagonist (OP449) is cytotoxic to CML cells, including the highly-resistant BCR-ABLT315I mutant, and demonstrates enhanced efficacy in combination with ABL tyrosine kinase inhibitors. Blood. 2011 Nov 18;118(21):3757.

[6]. Agarwal A, et al. Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research. 2014 Apr 15;20(8):2092-103.

[7]. Perl AL. Leveraging Small Molecule Activators of Protein Phosphatase 2A (PP2A) to Elucidate PP2As Role in Regulating DNA Replication and Apoptosis. Case Western Reserve University; 2020.

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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COG449

All Akt Isoforms

All ERK Isoforms

All NF-κB Isoforms

All Histone Acetyltransferase Isoforms