GDC-0575 free base | CAS#1196541-47-5 | CHK1 inhibitor

MedKoo Cat#: 584642 | Name: GDC-0575 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

GDC-0575, also known as ARRY-575 and RG7741, is a potent and selective inhibitor of cell cycle checkpoint kinase 1 (Chk1) with an IC50 of 1.2 nM. Chk1 inhibitor GDC-0575 specifically binds to and inhibits Chk1; this may result in tumor cells bypassing Chk1-dependent cell cycle arrest in the S and G2/M phases, which permits the cells to undergo DNA repair prior to entry into mitosis.

Chemical Structure

GDC-0575 free base

CAS#1196541-47-5 (free base)

Theoretical Analysis

MedKoo Cat#: 584642

Name: GDC-0575 free base

CAS#: 1196541-47-5 (free base)

Chemical Formula: C16H20BrN5O

Exact Mass: 377.0851

Molecular Weight: 378.27

Elemental Analysis: C, 50.80; H, 5.33; Br, 21.12; N, 18.51; O, 4.23

Price and Availability

Size	Price	Availability
10mg	USD 350.00	2 Weeks
25mg	USD 650.00	2 Weeks
50mg	USD 950.00	2 Weeks
100mg	USD 1,450.00	2 Weeks
200mg	USD 2,350.00	2 Weeks

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Related CAS #

1657014-42-0 (2HCl) 1196541-47-5 (free base) 1196504-54-7 (HCl)

Synonym

GDC-0575; GDC 0575; GDC0575; ARRY-575; ARRY 575; ARRY575; RG7741; RG-7741; RG 7741;

IUPAC/Chemical Name

(R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide

InChi Key

BAZRWWGASYWYGB-SNVBAGLBSA-N

InChi Code

InChI=1S/C16H20BrN5O/c17-11-6-19-15-13(14(11)22-5-1-2-10(18)8-22)12(7-20-15)21-16(23)9-3-4-9/h6-7,9-10H,1-5,8,18H2,(H,19,20)(H,21,23)/t10-/m1/s1

SMILES Code

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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

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

In vitro activity:

CHK1 inhibitor (CHK1i) GDC-0575 enhances AraC-mediated killing of AML cells both in vitro and in vivo, thus abrogating any potential chemoresistance mechanisms involving DNA repair. Reference: Nat Commun. 2017 Nov 22;8(1):1679. https://pubmed.ncbi.nlm.nih.gov/29162833/

In vivo activity:

The results indicated that GDC-0575 significantly inhibited the expression of colonic CHK1 in CAC (colitis-associated cancer) mice (Figure 1A). Further results indicated that the inhibition of CHK1 by GDC-0575 dramatically impaired the development of CAC in mice, as evidenced by the lower tumor count and smaller tumoral area in the colons of CAC mice compared to those of the control mice (Figure 1B–D). H&E staining also indicated that the tumors formed specifically in the colons of the CAC-DMSO group, and decreased tumor sizes were observed in the colons of the GDC-0575-treated mice with CAC (Figure 1E). The PCNA staining results indicated that GDC-0575 efficiently attenuated the proliferative ability of colonic cells in CAC mice (Figure 1F). Altogether, these results demonstrate that inhibition of CHK1 by GDC-0575 significantly impaired CAC development in mice. Reference: Onco Targets Ther. 2021 Apr 15;14:2661-2672. https://pubmed.ncbi.nlm.nih.gov/33897258/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	79.31
	DMSO	68.3	180.65
	DMSO:PBS (pH 7.2) (1:5)	0.2	0.42
	Ethanol	3.0	7.93

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 378.27 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Di Tullio A, Rouault-Pierre K, Abarrategi A, Mian S, Grey W, Gribben J, Stewart A, Blackwood E, Bonnet D. The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukemia. Nat Commun. 2017 Nov 22;8(1):1679. doi: 10.1038/s41467-017-01834-4. PMID: 29162833; PMCID: PMC5698422. 2. Li M, Huang T, Li X, Shi Z, Sheng Y, Hu M, Song K. GDC-0575, a CHK1 Inhibitor, Impairs the Development of Colitis and Colitis-Associated Cancer by Inhibiting CCR2+ Macrophage Infiltration in Mice. Onco Targets Ther. 2021 Apr 15;14:2661-2672. doi: 10.2147/OTT.S297132. PMID: 33897258; PMCID: PMC8058335.

In vitro protocol:

In vivo protocol:

1. Li M, Huang T, Li X, Shi Z, Sheng Y, Hu M, Song K. GDC-0575, a CHK1 Inhibitor, Impairs the Development of Colitis and Colitis-Associated Cancer by Inhibiting CCR2+ Macrophage Infiltration in Mice. Onco Targets Ther. 2021 Apr 15;14:2661-2672. doi: 10.2147/OTT.S297132. PMID: 33897258; PMCID: PMC8058335.

1: Grellety T, Callens C, Richard E, Briaux A, Vélasco V, Pulido M, Gonçalvès A, Gestraud P, MacGrogan G, Bonnefoi H, Cardinaud B. Enhancing abiraterone acetate efficacy in androgen receptor-positive triple negative breast cancer: Chk1 as a potential target. Clin Cancer Res. 2018 Oct 23. pii: clincanres.1469.2018. doi: 10.1158/1078-0432.CCR-18-1469. [Epub ahead of print] PubMed PMID: 30352905. 2: Italiano A, Infante JR, Shapiro GI, Moore KN, LoRusso PM, Hamilton E, Cousin S, Toulmonde M, Postel-Vinay S, Tolaney S, Blackwood EM, Mahrus S, Peale FV, Lu X, Moein A, Epler J, DuPree K, Tagen M, Murray ER, Schutzman JL, Lauchle JO, Hollebecque A, Soria JC. Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors. Ann Oncol. 2018 Feb 23. doi: 10.1093/annonc/mdy076. [Epub ahead of print] PubMed PMID: 29788155. 3: Oo ZY, Stevenson AJ, Proctor M, Daignault SM, Walpole S, Lanagan C, Chen J, Škalamera D, Spoerri L, Ainger SA, Sturm RA, Haass NK, Gabrielli B. Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors In Vivo. Clin Cancer Res. 2018 Jun 15;24(12):2901-2912. doi: 10.1158/1078-0432.CCR-17-2701. Epub 2018 Mar 13. PubMed PMID: 29535131. 4: Laroche-Clary A, Lucchesi C, Rey C, Verbeke S, Bourdon A, Chaire V, Algéo MP, Cousin S, Toulmonde M, Vélasco V, Shutzman J, Savina A, Le Loarer F, Italiano A. CHK1 inhibition in soft-tissue sarcomas: biological and clinical implications. Ann Oncol. 2018 Apr 1;29(4):1023-1029. doi: 10.1093/annonc/mdy039. PubMed PMID: 29409053. 5: Di Tullio A, Rouault-Pierre K, Abarrategi A, Mian S, Grey W, Gribben J, Stewart A, Blackwood E, Bonnet D. The combination of CHK1 inhibitor with G-CSF overrides cytarabine resistance in human acute myeloid leukemia. Nat Commun. 2017 Nov 22;8(1):1679. doi: 10.1038/s41467-017-01834-4. PubMed PMID: 29162833; PubMed Central PMCID: PMC5698422.