GDC-0575 (ARRY-575)

For research use only.

Catalog No.S8526 Synonyms: RG7741

3 publications

GDC-0575 (ARRY-575) Chemical Structure

CAS No. 1196541-47-5

GDC-0575 (ARRY-575, RG7741) is a potent and selective CHK1 inhibitor with an IC50 of 1.2 nM.

Selleck's GDC-0575 (ARRY-575) has been cited by 3 publications

Purity & Quality Control

Choose Selective Chk Inhibitors

Biological Activity

Description GDC-0575 (ARRY-575, RG7741) is a potent and selective CHK1 inhibitor with an IC50 of 1.2 nM.
Targets
Chk1 [1]
(Cell-free assay)
1.2 nM
In vitro

GDC-0575 enhances the cytotoxicity of Cytarabine (AraC) in vitro[1].

Assay
Methods Test Index PMID
Western blot
pCHK1 / pRPA2 / RPA2 / RRM2 / γH2AX / α-tub; 

PubMed: 31044505     


Low‐dose HU enhances replication stress in cancer cell lines. The indicated melanoma TS (A) and NSCLC cell lines (B) were treated for 24 h with the indicated combinations of 0.5 μm GDC‐0575 and 0.2 mm HU and then harvested and whole‐cell lysates immunoblotted for the indicated replication stress markers. The cell lines are in order of sensitivity to the combination, left to right, most to least sensitive. The hyperphosphorylated form of RPA2 is indicated by the arrowhead. Longer exposure of γH2AX staining demonstrates the low levels in the less sensitive TSs. α‐Tubulin was used as the loading control.

pCHK2 / pCHK1 / p53 / pRPA2 / RPA2 / RRM2 / γH2AX / α-tub; 

PubMed: 31044505     


(E) Immunoblot of the indicated proteins and markers of DNA damage and replication stress after 48 h of the indicated treatments. These are representative of replicate experiments. Significance was assessed by two‐tailed t‐test.

tPARP / cPARP / γH2AX / Tubulin; 

PubMed: 31649026     


(E, F) EW8 (E) and TC71 (F) cells were released from a thymidine double block in the presence of drugs, in the presence of LY2603618 (1 μM), GDC-0575 (1 μM), AZD6738 (1 μM), or DMSO for 4 h. Cell lysates were then collected for immunoblotting.

31044505 31649026
Growth inhibition assay
tumor volume; 

PubMed: 31044505     


Combination of HU and GDC‐0575 controls tumour growth. (A) Melanoma (C013, A2058) and NSCLC (H358) xenografts were established in nude mice and treated with either vehicle (Con), HU or HU + GDC‐0575 using a schedule of 20 mg·kg−1 GDC‐0575 + 100 mg·kg−1 HU by oral gavage, followed 4 h later by 50 mg·kg−1 HU ip, only alternate days three times a week for 3 weeks. Each point represents the mean of 4–6 mice, and the error represents SD. In the case of H358, the combination‐treated mice were allowed to continue for a further 30 days after the final treatment. The arrows indicate the treatments. Significance was assessed by two‐way ANOVA for comparison of control and HU‐treated against HU + GDC‐treated samples. There was no difference between control and HU‐treated samples.

31044505
IHC
H&E staining / PCNA expression; 

PubMed: 33897258     


(E) H&E staining of colons from colons from CAC mice treated with DMSO or GDC-0575. The tumor area in each frame was analyzed (n=4, **p<0.01). Scale bar = 200 μm. (F) IHC staining of PCNA expression in colons of CAC mice treated with DMSO or GDC-0575. The percentage of PCNA positive cells in each frame was analyzed. Scale bar = 100 μm, **p<0.01.

H&E staining; 

PubMed: 33897258     


(H) H&E staining of colons from colons from colitis mice treated with DMSO or GDC-0575. The histologic score was analyzed (n=5, **p<0.01; Scale bar = 200 μm).

Small intestine / Colon; 

PubMed: 31044505     


Combination of HU and GDC‐0575 controls tumour growth. (B) H&E staining of small intestines and colon from either control or combination‐treated mice killed the day after final treatment. Images were taken at 20× magnification. 60× magnification of the indicated regions in the base of the crypts shows apoptotic cells (arrowheads).

33897258 31044505
Immunofluorescence
F4/80 / iNOS; 

PubMed: 33897258     


(B) Immunofluorescence staining of F4/80 and iNOS expression in colons of CAC mice treated with DMSO or GDC-0575. The percentage of F4/80 and iNOS positive cells in each frame was analyzed (n=3, **p<0.01; Scale bar = 200 μm).

F4/80 / iNOS; 

PubMed: 33897258     


(C) Immunofluorescence staining of F4/80 and iNOS expression in colons of colitis mice treated with DMSO or GDC-0575. The percentage of F4/80 and iNOS positive cells in each frame was analyzed (n=3, **p<0.01; Scale bar = 200 μm).

F4/80 / CCR2; 

PubMed: 33897258     


(C) Immunofluorescence staining of F4/80 and CCR2 expression in colons of CAC mice treated with DMSO or GDC-0575. The percentage of F4/80 and CCR2 positive cells in each frame was analyzed (n=3, **p<0.01; Scale bar = 200 μm).

F4/80 / CCR2; 

PubMed: 33897258     


(D) Immunofluorescence staining of F4/80 and CCR2 expression in colons of colitis mice treated with DMSO or GDC-0575. The percentage of F4/80 and CCR2 positive cells in each frame was analyzed (n=3, **p<0.01; Scale bar = 200 μm).

33897258
In vivo

GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models[2].

Protocol

Solubility (25°C)

In vitro DMSO 75 mg/mL (198.27 mM)
Water Insoluble
Ethanol '5 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 378.27
Formula

C16H20BrN5O

CAS No. 1196541-47-5
Storage powder
in solvent
Synonyms RG7741
Smiles C1CC(CN(C1)C2=C3C(=CNC3=NC=C2Br)NC(=O)C4CC4)N

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01564251 Completed Drug: GDC-0575|Drug: Gemcitabine Lymphoma Solid Tumor Genentech Inc. March 23 2012 Phase 1

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Chk Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID