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

GDC-0575 dihydrochloride (Synonyms: ARRY-575 dihydrochloride; RG7741 dihydrochloride)

Cat. No.: HY-112167A Purity: 99.32%
Handling Instructions

GDC-0575 dihydrochloride is an orally bioavailable CHK1 inhibitor, with an IC50 of 1.2 nM, and has antitumor activity.

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

GDC-0575 dihydrochloride Chemical Structure

GDC-0575 dihydrochloride Chemical Structure

CAS No. : 1657014-42-0

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 264 In-stock
Estimated Time of Arrival: December 31
5 mg USD 240 In-stock
Estimated Time of Arrival: December 31
10 mg USD 380 In-stock
Estimated Time of Arrival: December 31
25 mg USD 780 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1300 Get quote
100 mg USD 2100 Get quote
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of GDC-0575 dihydrochloride:

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

GDC-0575 dihydrochloride is an orally bioavailable CHK1 inhibitor, with an IC50 of 1.2 nM, and has antitumor activity.

IC50 & Target[1]

Chk1

1.2 nM (IC50)

In Vitro

GDC-0575 dihydrochloride is a selective and orally bioavailable CHK1 inhibitor, with an IC50 of 1.2 nM. GDC-0575 (100 nM) suppressses CHK1 activation induced by AraC by decreasing the level of Tyr15-phosphorylated CDK2. GDC-0575 (100 nM) has no effect on the viability of AML cells, but significantly reduces cell viability and induces apoptosis in combination with AraC. In addition, GDC-0575 plus AraC shows no effect on normal hematopoietic stem and progenitor cells (HSPCs)[1]. GDC-0575 shows cytotoxic activity against most of 20 melanoma cell lines tested, but several cell lines grown as tumour sphere (TS) are relatively insensitive[2].

In Vivo

GDC-0575 (7.5 mg/kg, p.o.) in combination with AraC alomost completely eradicates leukemic burden in mice transplanted with U937-Luc cells, and shows more efficient activity than AraC alone. Furthermore, GDC-0575 elevates the cytotoxicity of AraC in different primary AML models in vivo[1]. GDC-0575 (25, 50 mg/kg, p.o.) dose-dependently inhibits the growth of tumor in D20 and C002 xenografts[2].

Clinical Trial
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100.3 mg/mL (222.30 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.2164 mL 11.0818 mL 22.1636 mL
5 mM 0.4433 mL 2.2164 mL 4.4327 mL
10 mM 0.2216 mL 1.1082 mL 2.2164 mL
*Please refer to the solubility information to select the appropriate solvent.
References
Cell Assay
[1]

For co-culture experiments, 2 days before initiating the co-culture, feeder cells are plated onto type-I collagen-coated 96-well or 6-well plates and allowed to reach confluence. One day before starting co-culture, they are irradiated at 6.8 Gy and the culture media exchanged. On day 0 of the co-culture, AmL cells are plated at 2 × 105 cells/mL using the correspondent AmL medium. Cells are cultured at 37°C in 5% CO2-humidified incubators at indicated oxygen concentrations. For short-term culture (STC), cells are kept for 1 week in hypoxia (5% O2) with the indicated drugs: 500 nM AraC and/or 100 nM GDC-0575[1].

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

Animal Administration
[1]

Mice[1]
NSG mice are injected intravenously with 1 × 105-106 cells of AmL and 1-3 × 105 cells of hCB CD34+/hBM CD34+. After demonstrating AmL engraftment at 9-11 weeks through FACS analysis of tibia bone marrow aspiration, mice are treated accordingly to proper 7-day treatment regimen with daily 10 mg/kg AraC via subcutaneous injection, 7.5 mg/kg GDC-0575 suspension administered via oral gavage on every other day schedule, and/or 300 μg/kg G-CSF administered daily for 5 days via intraperitoneal injection. One week after the final dosing, mice are killed by cervical dislocation. The femurs, tibias, and pelvis are dissected and flushed with PBS. Red blood cells are lyzed via ammonium chloride. Cells are stained with human-specific FITC-conjugated anti-CD19, PE-conjugated anti-CD33, PE-Cy7-conjugated anti-CD45, and PERCP-conjugated anti-murine CD45 antibodies. Dead cells and debris are excluded via DAPI staining. A BD LSR II flow cytometer is used for analysis. Flow cytometry analysis is performed with FlowJo software. More than 100,000 DAPI-negative events are collected. Engraftment of AmL is said to be present if a single population of mCD45-hCD45+CD33+CD19- cells is present without accompanying mCD45-hCD45+CD33−CD19+cells[1].

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

References
Molecular Weight

451.19

Formula

C₁₆H₂₂BrCl₂N₅O

CAS No.

1657014-42-0

SMILES

O=C(C1CC1)NC2=CNC3=NC=C(Br)C(N4C[[email protected]](N)CCC4)=C32.[2HCl]

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

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Product Name:
GDC-0575 dihydrochloride
Cat. No.:
HY-112167A
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GDC-0575 dihydrochloride

Cat. No.: HY-112167A