WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406593
CAS#: 1457983-28-6
Description: G-749 is a novel FLT3 inhibitor that showed potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G-749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. Furthermore, it displayed potent antileukemic activity in bone marrow blasts from AML patients regardless of FLT3 mutation status, including those with little or only minor responses to AC220 or PKC412. Oral administration of G-749 yielded complete tumor regression and increased life span in animal models. Thus, G-749 appears to be a promising next-generation drug candidate for the treatment of relapsed and refractory AML patients with various FLT3-ITD/FLT3-TKD mutants and further shows the ability to overcome drug resistance (Blood. 2014 Apr 3;123(14):2209-19).
MedKoo Cat#: 406593
Name: G-749
CAS#: 1457983-28-6
Chemical Formula: C25H25BrN6O2
Exact Mass: 520.12224
Molecular Weight: 521.41
Elemental Analysis: C, 57.59; H, 4.83; Br, 15.32; N, 16.12; O, 6.14
Synonym: G749; G-749; G 749; denfivontinib
IUPAC/Chemical Name: 8-bromo-2-((1-methylpiperidin-4-yl)amino)-4-((4-phenoxyphenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one
InChi Key: SXWMIXPJPNCXQQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H25BrN6O2/c1-32-13-11-17(12-14-32)29-25-30-22-20(26)15-27-24(33)21(22)23(31-25)28-16-7-9-19(10-8-16)34-18-5-3-2-4-6-18/h2-10,15,17H,11-14H2,1H3,(H,27,33)(H2,28,29,30,31)
SMILES Code: O=C1NC=C(Br)C2=NC(NC3CCN(C)CC3)=NC(NC4=CC=C(OC5=CC=CC=C5)C=C4)=C21
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: | G-749 is a potent, oral active and ATP competitive FLT3 inhibitor, with IC50s of 0.4 nM and 0.6 nM for FLT3 wild type and FLT3-D835Y, respectively. |
| In vitro activity: | Potent inhibition of FLT3 was confirmed in leukemia cells where G-749 inhibited autophosphorylation of FLT3 with an IC50 value of ≤8 nM in FLT3-WT bearing RS4-11 and in FLT3-ITD harboring MV4-11 and Molm-14 cells (Figure 1C and supplemental Figure 3A-B). Reference: Blood. 2014 Apr 3; 123(14): 2209–2219. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975259/ |
| In vivo activity: | To assess the in vivo pharmacodynamic effect of G-749, a single dose of G-749 HCl salt (10 mg/kg) was administered orally to subcutaneous MV4-11 xenograft mice and showed sustained inhibition of p-FLT3, p-STAT5, and p-ERK1/2 (Figure 5A-B). These data indicate that G-749 effectively inhibits the FLT3 pathway and that its inhibition lasts for 24 hours. Reference: Blood. 2014 Apr 3; 123(14): 2209–2219. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975259/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 17.33 | 33.24 | |
| DMF | 16.0 | 30.69 | |
| DMF:PBS (pH 7.2) (1:3) | 0.25 | 0.48 |
The following data is based on the product molecular weight 521.41 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. Lee HK, Kim HW, Lee IY, Lee J, Lee J, Jung DS, Lee SY, Park SH, Hwang H, Choi JS, Kim JH, Kim SW, Kim JK, Cools J, Koh JS, Song HJ. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19. doi: 10.1182/blood-2013-04-493916. Epub 2014 Feb 14. PMID: 24532805; PMCID: PMC3975259. |
| In vitro protocol: | 1. Lee HK, Kim HW, Lee IY, Lee J, Lee J, Jung DS, Lee SY, Park SH, Hwang H, Choi JS, Kim JH, Kim SW, Kim JK, Cools J, Koh JS, Song HJ. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19. doi: 10.1182/blood-2013-04-493916. Epub 2014 Feb 14. PMID: 24532805; PMCID: PMC3975259. |
| In vivo protocol: | 1. Lee HK, Kim HW, Lee IY, Lee J, Lee J, Jung DS, Lee SY, Park SH, Hwang H, Choi JS, Kim JH, Kim SW, Kim JK, Cools J, Koh JS, Song HJ. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19. doi: 10.1182/blood-2013-04-493916. Epub 2014 Feb 14. PMID: 24532805; PMCID: PMC3975259. |
1: Lee HK, Kim HW, Lee IY, Lee J, Lee J, Jung DS, Lee SY, Park SH, Hwang H, Choi JS, Kim JH, Kim SW, Kim JK, Cools J, Koh JS, Song HJ. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19. doi: 10.1182/blood-2013-04-493916. Epub 2014 Feb 14. PubMed PMID: 24532805; PubMed Central PMCID: PMC3975259.
