GDC-0575 freebase

• CAS: 1196541-47-5
• Catalog Number: ACM1196541475
• Category: Inhibitors
• Molecular Weight: 378.27
• Molecular Formula: C16H20BrN5O
• Description: 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.
• Synonyms: GDC-0575; GDC 0575; GDC0575; ARRY-575; ARRY-575; ARRY575; RG7741; RG-7741; RG 7741; AK 687476; AK-687476; AK687476; GDC-0575 HCl; GDC-0575 hydrochloride
• IUPAC Name: (R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclopropanecarboxamide
• Canonical SMILES: O=C(C1CC1)NC2=CNC3=NC=C(Br)C(N4C[C@H](N)CCC4)=C32
• InChI: 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
• InChI Key: BAZRWWGASYWYGB-SNVBAGLBSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1657014-42-0 (2HCl); 1196541-47-5 (free base); 1196504-54-7 (HCl)
• Biological Target: GDC-0575 (ARRY-575, RG7741) is a highly-selective oral small-molecule Chk1 inhibitor with an IC50 of 1.2 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 50.80; H, 5.33; Br, 21.12; N, 18.51; O, 4.23
• Exact Mass: 377.0851
• HS Tariff Code: 2934.99.9001
• 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/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).