1. Cell Cycle/DNA Damage
  2. Checkpoint Kinase (Chk)

GDC-0575 (Synonyms: ARRY-575, RG7741)

Cat. No.: HY-112167
Handling Instructions

GDC-0575 (ARRY-575, RG7741) is a highly-selective oral small-molecule Chk1 inhibitor with an IC50 of 1.2 nM.

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

GDC-0575 Chemical Structure

GDC-0575 Chemical Structure

CAS No. : 1196541-47-5

Size Price Stock
5 mg USD 240 Get quote
10 mg USD 380 Get quote
25 mg USD 780 Get quote
50 mg USD 1300 Get quote
100 mg USD 2100 Get quote

* Please select Quantity before adding items.

View All Checkpoint Kinase (Chk) Isoform Specific Products:

  • Biological Activity

  • Protocol

  • Technical Information

  • References

Description

GDC-0575 (ARRY-575, RG7741) is a highly-selective oral small-molecule Chk1 inhibitor with an IC50 of 1.2 nM.

IC50 & Target

1.2 nM (Chk1)[1]

In Vitro

GDC-0575 is significantly more potent in promoting DNA damage, replication stress and cell death than V158411, LY2603618, and MK-8776 in a panel of melanoma cell lines[1]. GDC-0575 abrogates DNA damage-induced S and G2–M checkpoints, exacerbates DNA double-strand breaks and induces apoptosis in STS cells. GDC-0575 has a synergistic or additive effect together with gemcitabine[2]. CHK1 inhibitor GDC-0575 in combination with AraC enhances the killing of primary acute myeloid leukemia cells ex vivo by inducing apoptosis[3].

In Vivo

GDC-0575 is active at 25 mg/kg as a single agent, but the efficacy is improved at the higher drug dose. GDC-0575 effectively blocks tumor growth in the D20 and C002 xenografts, and the effect is maintained for at least 10 days after the final dose is administered[1].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.6436 mL 13.2181 mL 26.4361 mL
5 mM 0.5287 mL 2.6436 mL 5.2872 mL
10 mM 0.2644 mL 1.3218 mL 2.6436 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[3]

GDC-0575 (100 μM) are stored at −20 °C and used at a final concentration of 100 nM.

AML cell lines are seeded at 1×104 cells/well in 96-well plates in triplicate, and subjected to different treatment conditions. After 24 h of incubation with GDC-0575, cell proliferation is measured with the XTT Cell Proliferation Kit II[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

GDC-0575 is prepared in 0.5% w/v methylcellulose and 0.2%v/v Tween 80[1].

Mice[1]

Female nude BALB/c mice are injected with 2-3×106 melanoma cells in Matrigel by subcutaneous injection on the hind flank. Once tumors reach approximately 100 mm3, mice are treated with GDC-0575 (25 mg/kg, 50 mg/kg) or vehicle (0.5% w/v methylcellulose and 0.2%v/v Tween 80) by oral gavage for 3 cycles where one cycle is three consecutive days of treatment followed by four rest days. Tumor size is measured three times per week using calipers. Mice are sacrificed at up to 6 weeks after terminating the treatment or when tumor size measured >1 cm3[1].

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

References
Molecular Weight

378.27

Formula

C₁₆H₂₀BrN₅O

CAS No.

1196541-47-5

SMILES

O=C(C1CC1)NC2=CNC3=NC=C(Br)C(N4C[[email protected]](N)CCC4)=C32

Storage

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

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country or Region *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
GDC-0575
Cat. No.:
HY-112167
Quantity: