Cat. No.: HY-187643

CGC-11144 hydrochloride

CGC-11144 hydrochloride is a polyamine analog. CGC-11144 hydrochloride reduces the kinase activities of CDK4, CDK2 and CDK6, induces activation of the p53 pathway and p53-dependent p21 expression, and mediates cell cycle regulation, growth inhibition and apoptosis. CGC-11144 hydrochloride induces G1 phase cell cycle arrest, downregulates cyclin D1 and cyclin B1, upregulates cyclin E, induces dephosphorylation of pRb, and inhibits ERα-mediated transcriptional activity by disrupting the DNA binding of Sp1/Sp3 to the ERα promoter, while also stimulating activation of the JNK/AP-1 pathway. CGC-11144 hydrochloride can be used in research related to breast cancer, choroidal neovascularization and cancer.

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

CAS No.: 304911-07-7
Formula: C₄₀H₉₁ClN₁₀
Molecular Weight:747.67

Storage:

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

CGC-11144 hydrochloride Chemical Structure

CAS No.: 304911-07-7

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Use of MCE Products

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

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

Biological Activity

Description

IC₅₀ & Target

^[4]^[5]^[6]^[1]^[2]^[3]

p53

p21

Cyclin B1

pRb

Sp1

Sp3

AP-1

CDK2/cyclinE

CDK4

CDK6/cyclinD1

JNK

All CDK Isoforms :

All Estrogen Receptor/ERR Isoforms :

All JNK Isoforms :

All AP-1 Isoforms :

In Vitro

CGC-11144 (0.1-100 μM; 96 h) hydrochloride potently inhibits the growth of human breast cancer MCF-7 cells with an IC₅₀ of 0.75-1.5 μM after 96 h^[1].
CGC-11144 (0.5-10 μM; 4-96 h) hydrochloride specifically down-regulates ERα and its target gene protein expression in a time- and concentration-dependent manner in ER-positive human breast cancer MCF-7 and T47D cells, with a minimum effective concentration of 5 μM^[2].
CGC-11144 (10 μM; 24-96 h) hydrochloride reduces nuclear ERα levels and inhibits ER-mediated transcriptional activity in ER-positive human breast cancer MCF-7 and T47D cells treated with 10 nM 17β-Estradiol (Estradiol) (HY-B0141)^[2].
CGC-11144 (10 μM; 24-96 h) hydrochloride down-regulates ERα expression via transcriptional repression of the ERα promoter, reducing ERα mRNA levels in ER-positive human breast cancer MCF-7 and T47D cells^[2].
CGC-11144 (10 μM; 72 h) hydrochloride does not affect the expression of exogenous CMV promoter-driven ERα in ER-negative human breast cancer MDA-MB-231-ER19 cells, confirming its effect is specific to ERα promoter transcription rather than protein stability^[2].
CGC-11144 (10 μM; 24 h) hydrochloride inhibits ERα proximal promoter activity in ER-positive human breast cancer T47D cells by disrupting Sp1 and Sp3 recruitment to the promoter without changing Sp1 or Sp3 protein expression^[2].
CGC-11144 (10 μM; 72-96 h) hydrochloride activates the JNK/AP-1 pathway, which acts as a positive regulator of ERα expression in ER-positive human breast cancer MCF-7 cells; inhibiting this pathway enhances CGC-11144-induced ERα down-regulation, with the effect occurring via the endogenous ERα promoter rather than ERα protein itself^[2].
CGC-11144 (10 μM; 72 h) hydrochloride arrests human breast cancer MCF-7 cells at the G₁ phase of the cell cycle^[1].
CGC-11144 (10 μM; 24-96 h) hydrochloride upregulates p53 and p21, downregulates cyclin D1 and cyclin B1, upregulates cyclin E, and induces complete pRb dephosphorylation in human breast cancer MCF-7 cells^[1].
CGC-11144 (10 μM; 96 h) hydrochloride in human breast cancer MCF-7 cells, p53 siRNA blocks p21 induction, reverses CDK4 inhibition, partially reverses CDK6 inhibition, but does not alter cyclin D1/cyclin B1 downregulation or CDK2 inhibition^[1].
CGC-11144 (10 μM; 96 h) hydrochloride-induced G₁ cell cycle arrest in human breast cancer MCF-7 cells is not reversed by suppression of p53 expression via siRNA^[1].
CGC-11144 (10 μM; 96 h) hydrochloride-induced apoptotic DNA fragmentation in human breast cancer MCF-7 cells is suppressed by p53 siRNA-mediated knockdown of p53 expression^[1].
CGC-11144 (10 μM; 3 h) hydrochloride potently induces antizyme activity in HTC cells, reaching levels 200% relative to Spermine (HY-B1777)-induced antizyme activity after 3 h exposure to 10 μM^[4].
CGC-11144 (1.0 μM; 24 h) hydrochloride is highly cytotoxic to CHO cells, causing minimal analog accumulation, a slight reduction in total cellular polyamine content, and near-complete cell detachment after 24 h exposure to 1.0 μM^[4].
CGC-11144 (0.25-5 μM; 24 h) hydrochloride is accumulated in minimal amounts by CHO cells, with cellular incorporation remaining largely unchanged across extracellular concentrations from 0.25 μM to 5 μM after 24 h exposure^[4].
CGC-11144 (15 min) hydrochloride potently induces oligomerization of reconstituted chicken erythrocyte histone-Lytechinus variegatus 208-11S DNA nucleosomal arrays with a EC₅₀ of 4 μM, and this activity remains potent even in the presence of 80 μM Spermidine (HY-B1776)^[6].
CGC-11144 (10-100 μM; 2-8 h) hydrochloride potently inhibits the growth of CY1019 yeast cells, blocking growth at 40 μM and inducing G₁ phase accumulation, with this activity not attributed to enhanced cellular uptake relative to group I analogues^[6].

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

Cell Viability Assay^[1]

Cell Line:

human breast cancer MCF-7 cells (wild-type p53)
Concentration:

0.1 μM; 1 μM; 10 μM; 100 μM
Incubation Time:

96 h
Result:

Inhibited MCF-7 cell growth in a concentration-dependent manner, with an IC₅₀ value of 0.75-1.5 μM after 96 h.

Cell Cycle Analysis^[1]

Cell Line:

human breast cancer MCF-7 cells (wild-type p53)
Concentration:

10 μM
Incubation Time:

72 h
Result:

Increased the proportion of MCF-7 cells in the G₁ phase to 74.35% (from 53.1% in untreated cells).
Decreased the G₂/M phase proportion to 10.85% (from 25.7% in untreated cells).
Reduced the S phase proportion to 3.9% (from 11.9% in untreated cells), indicating a G₁ cell cycle arrest.

Western Blot Analysis^[1]

Cell Line:

human breast cancer MCF-7 cells (wild-type p53)
Concentration:

10 μM
Incubation Time:

24-96 h
Result:

Induced time-dependent increases in p53 and p21 protein expression, with elevated levels visible by 48 h and further increases through 96 h.
Downregulated cyclin D1 protein levels after 72 h treatment.
Downregulated cyclin B1 protein levels.
Increased cyclin E protein expression.
Caused complete dephosphorylation of retinoblastoma protein (pRb).
Left expression of p27 and p15 proteins unchanged.

Apoptosis Analysis^[1]

Cell Line:

human breast cancer MCF-7 cells stably transfected with p53 siRNA or empty vector
Concentration:

10 μM
Incubation Time:

96 h
Result:

Induced internucleosomal DNA fragmentation (a marker of apoptosis) in empty vector-transfected MCF-7 cells.
Inhibited DNA fragmentation in p53 siRNA-transfected cells.

Western Blot Analysis^[1]

Cell Line:

human breast cancer MCF-7 cells stably transfected with p53 siRNA or empty vector
Concentration:

10 μM
Incubation Time:

96 h
Result:

Induced p21 expression, downregulated cyclin D1 and cyclin B1, and inhibited CDK4, CDK6, and CDK2 kinase activities in empty vector-transfected cells.
Blocked induction of p21, reversed inhibition of CDK4 activity, partially reversed inhibition of CDK6 activity, and left downregulation of cyclin D1 and cyclin B1 and inhibition of CDK2 activity unchanged in p53 siRNA-transfected cells.

Cell Cycle Analysis^[1]

Cell Line:

human breast cancer MCF-7 cells stably transfected with p53 siRNA or empty vector
Concentration:

10 μM
Incubation Time:

96 h
Result:

Induced G₁ arrest in empty vector-transfected cells, with 65.3% of cells in G₁, 5.7% in S, and 19.6% in G₂/M.
Maintained G₁ arrest in p53 siRNA-transfected cells, with 69.6% of cells in G₁, 5.6% in S, and 15.6% in G₂/M.

Western Blot Analysis^[2]

Cell Line:

ER-positive human breast cancer MCF-7 and T47D cells
Concentration:

0.5-10 μM (MCF-7 cells, 96 h; T47D cells, 24 h); 10 μM (MCF-7 cells, 24-96 h; T47D cells, 4-24 h)
Incubation Time:

24-96 h (MCF-7 cells); 4-24 h (T47D cells)
Result:

Specifically down-regulated ERα protein expression, while leaving ERβ, vitamin D receptor, and retinoic acid receptor β protein levels unchanged.
Inhibited the expression of ERα target genes progesterone receptors (PRA and PRB) and cyclin D1.
Reduced ERα expression after 72 h in MCF-7 cells and after 16 h in T47D cells.
Required a minimum 5 μM concentration to decrease ERα protein in both cell lines after respective incubation times.

Western Blot Analysis^[2]

Cell Line:

ER-negative human breast cancer MDA-MB-231-ER19 cells
Concentration:

10 μM
Incubation Time:

72 h
Result:

Did not alter the protein level of exogenous CMV promoter-driven ERα.

Cell Viability Assay^[3]

Cell Line:

53 well-characterized breast cancer cell lines
Concentration:

0.5 μM - 20 mM
Incubation Time:

72 h
Result:

Revealed significant variation in Hill slope values across 53 breast cancer cell lines.

In Vivo

CGC-11144 hydrochloride (10-20 mg/kg; i.p.; twice or three times per week; 2-20 μg; 0.2 mg; 200 μg; intravitreal administration; periocular administration; various frequencies and durations) reduces the incidence of laser-induced choroidal neovascularization by approximately 40% and promotes its regression; among these administration routes, periocular administration causes no retinal toxicity, while intravitreal administration induces dose-dependent retinal damage^[5].

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

Animal Model:

C57BL/6J (4- to 5-week-old female); C57BL/6 (adult female)^[5]
Dosage:

10 mg/kg; 20 mg/kg; 20 μg; 2 μg; 4 μg; 0.2 mg; 200 μg
Administration:

i.p.; twice weekly; 2 weeks; i.p.; three times weekly; 2 weeks; intravitreous; days 0 and 7 post-rupture; intravitreous; days 7 and 10 post-rupture; periocular; three times weekly; 2 weeks; periocular; days 7, 10, and 13 post-rupture; periocular; daily from days 7 to 14 post-rupture; intravitreous; single injection; periocular; single injection on days 7 and 8 post-rupture
Result:

Caused small but significant reductions in CNV area (10 mg/kg and 20 mg/kg i.p. surviving mice).
Reduced CNV area by ~40% (20 μg intravitreous on days 0 and 7).
Induced significant regression of pre-existing CNV (20 μg intravitreous on days 7 and 10).
Reduced ERG b-wave amplitudes across all flash intensities and caused mild a-wave reduction at highest flash intensities (2 μg intravitreous single injection).
Reduced ERG a-wave and b-wave amplitudes (4 μg or 20 μg intravitreous single injection).
Caused marked disruption of retinal structure (20 μg intravitreous single injection).
Reduced CNV area by ~40% (0.2 mg periocular three times weekly for 2 weeks).
Induced significant regression of established CNV (200 μg periocular on days 7, 10, and 13; 200 μg periocular daily from days 7 to 14).
Did not alter ERG a- or b-wave amplitudes or retinal structure (200 μg periocular daily from days 7 to 14).
Induced apoptosis in CNV lesions, with no detectable apoptosis in normal retinal cells or blood vessels (0.2 mg periocular single injection on days 7 and 8).

Chemical Information

CAS No. 304911-07-7
Molecular Weight 747.67
Formula C₄₀H₉₁ClN₁₀
SMILES

CCNCCCCNCCCCNCCCCNCCCCNC/C=C\CNCCCCNCCCCNCCCCNCCCCNCC.Cl.[10]
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]. Huang Y, et al. Role of p53/p21(Waf1/Cip1) in the regulation of polyamine analogue-induced growth inhibition and cell death in human breast cancer cells. Cancer Biol Ther. 2005 Sep;4(9):1006-13.

[2]. Huang Y, et al. Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells. The Journal of biological chemistry. 2006 Jul 14;281(28):19055-63.

[3]. Fallahi-Sichani M, et al. Metrics other than potency reveal systematic variation in responses to cancer drugs. Nature chemical biology. 2013 Nov;9(11):708-14.

[4]. Mitchell JL, et al. Antizyme and antizyme inhibitor activities influence cellular responses to polyamine analogs. Amino acids. 2007 Aug;33(2):291-7.

[5]. Lima e Silva R, et al. Suppression and regression of choroidal neovascularization by polyamine analogues. Investigative ophthalmology & visual science. 2005 Sep;46(9):3323-30.

[6]. Carruthers LM, et al. Polyamine analogues: potent inducers of nucleosomal array oligomerization and inhibitors of yeast cell growth. The Biochemical journal. 2007 Aug 01;405(3):541-5.

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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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CGC-11144 hydrochloride

All CDK Isoforms

All Estrogen Receptor/ERR Isoforms

All JNK Isoforms

All AP-1 Isoforms