WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406614
CAS#: 452342-37-9
Description: GW6604 is a potent and selective ALK-5 inhibitor with potent anticancer activity. GW6604 is also a TGF-beta signaling pathway inhibitor. In vitro, GW6604 inhibited autophosphorylation of ALK5 with an IC(50) of 140 nM and in a cellular assay inhibited TGF-beta-induced transcription of PAI-1 (IC(50): 500 nM). In vivo, GW6604 (40 mg kg(-1) p.o.) increased liver regeneration in TGF-beta-overexpressing mice, which had undergone partial hepatectomy. In an acute model of liver disease, GW6604 reduced by 80% the expression of collagen IA1. Inhibition of ALK5 could be an attractive new approach to treatment of liver fibrotic diseases by both preventing matrix deposition and promoting hepatocyte regeneration. ( Br J Pharmacol. 2005 May;145(2):166-77. ).
MedKoo Cat#: 406614
Name: GW6604
CAS#: 452342-37-9
Chemical Formula: C19H14N4
Exact Mass: 298.1218
Molecular Weight: 298.349
Elemental Analysis: C, 76.49; H, 4.73; N, 18.78
Synonym: GW6604; GW-6604; GW 6604.
IUPAC/Chemical Name: 2-phenyl-4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridine
InChi Key: BDCBRQYHYNUWAM-UHFFFAOYSA-N
InChi Code: InChI=1S/C19H14N4/c1-2-6-14(7-3-1)18-12-15(9-11-21-18)16-13-22-23-19(16)17-8-4-5-10-20-17/h1-13H,(H,22,23)
SMILES Code: C1(C2=CC=CC=C2)=NC=CC(C3=CNN=C3C4=NC=CC=C4)=C1
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, not in water
Shelf Life: >2 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
| Biological target: | GW6604 is a potent and selective ALK-5 inhibitor with potent anticancer activity. |
| In vitro activity: | As shown in Figure 2c, GW6604 inhibited ALK5 activity with an IC50 of 140 nm, a potency comparable to that measured in an ALK5 binding assay (IC50=107 nm (Table 1). Reference: Br J Pharmacol. 2005 May;145(2):166-77. https://pubmed.ncbi.nlm.nih.gov/15723089/ |
| In vivo activity: | Treatment with GW6604 induced a 4.7-fold increase in hepatocyte proliferation in partially hepatectomized TGF-β transgenic mice (1.8±0.4 and 8.5±2.2 stained nuclei per field in animals treated with vehicle and GW6604, respectively, P=0.02 (t-test)) (Figure 3). Reference: Br J Pharmacol. 2005 May;145(2):166-77. https://pubmed.ncbi.nlm.nih.gov/15723089/ |
The following data is based on the product molecular weight 298.349 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. de Gouville AC, Boullay V, Krysa G, Pilot J, Brusq JM, Loriolle F, Gauthier JM, Papworth SA, Laroze A, Gellibert F, Huet S. Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol. 2005 May;145(2):166-77. doi: 10.1038/sj.bjp.0706172. PMID: 15723089; PMCID: PMC1576127. |
| In vitro protocol: | 1. de Gouville AC, Boullay V, Krysa G, Pilot J, Brusq JM, Loriolle F, Gauthier JM, Papworth SA, Laroze A, Gellibert F, Huet S. Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol. 2005 May;145(2):166-77. doi: 10.1038/sj.bjp.0706172. PMID: 15723089; PMCID: PMC1576127. |
| In vivo protocol: | 1. de Gouville AC, Boullay V, Krysa G, Pilot J, Brusq JM, Loriolle F, Gauthier JM, Papworth SA, Laroze A, Gellibert F, Huet S. Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol. 2005 May;145(2):166-77. doi: 10.1038/sj.bjp.0706172. PMID: 15723089; PMCID: PMC1576127. |
1: Ciayadi R, Kelso GF, Potdar MK, Harris SJ, Walton KL, Harrison CA, Hearn MT. Identification of protein binding partners of ALK-5 kinase inhibitors. Bioorg Med Chem. 2013 Nov 1;21(21):6496-500. doi: 10.1016/j.bmc.2013.08.038. Epub 2013 Aug 29. PubMed PMID: 24055074.
2: de Gouville AC, Huet S. Inhibition of ALK5 as a new approach to treat liver fibrotic diseases. Drug News Perspect. 2006 Mar;19(2):85-90. Review. PubMed PMID: 16628263.
3: de Gouville AC, Boullay V, Krysa G, Pilot J, Brusq JM, Loriolle F, Gauthier JM, Papworth SA, Laroze A, Gellibert F, Huet S. Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol. 2005 May;145(2):166-77. PubMed PMID: 15723089; PubMed Central PMCID: PMC1576127.
