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Details

Stereochemistry ACHIRAL
Molecular Formula C25H25BrN6O2
Molecular Weight 521.4095
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of G-749

SMILES

CN1CCC(CC1)N=c2[nH]c3c(cnc(c3c(Nc4ccc(cc4)Oc5ccccc5)n2)O)Br

InChI

InChIKey=SXWMIXPJPNCXQQ-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C25H25BrN6O2
Molecular Weight 521.4095
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

G749 is a Fms-like tyrosine receptor kinase 3 (FLT3) inhibitor and a promising next-generation drug candidate for the treatment of relapsed and refractory acute myeloid leukemia (AML) patients with various FLT3-ITD/FLT3-TKD mutants that shows the ability to overcome drug resistance. It demonstrated 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. G749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. It also 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 G749 yielded complete tumor regression and increased life span in animal models.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P36888
Gene ID: 2322.0
Gene Symbol: FLT3
Target Organism: Homo sapiens (Human)
0.4 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia.
2014 Apr 3
Patents

Patents

Sample Use Guides

To examine its antitumor efficacy, G749 HCl salt was administered orally every day for 28 days to the MV4-11 xenograft mice.
Route of Administration: Oral
The antiproliferative activity of G749 was assessed in several leukemia cell lines. Five human leukemia cell lines seeded at a density of 2 × 10(4) cells per well were incubated with increasing concentrations of G749 (0.32, 1.6, 8, 40, 200, 1000, 5000 nM) for 72 hours at 37°C. G749 showed strong antiproliferation of leukemia cells addicted to FLT3-ITD (MV4-11 and Molm-14) in a dose-dependent manner, whereas it did not potently inhibit proliferation of leukemia cells without FLT3 expression (HEL and K562) or of non–FLT3-addicted cells with FLT3-WT (RS4-11).
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:56:47 UTC 2021
Edited
by admin
on Sat Jun 26 02:56:47 UTC 2021
Record UNII
B06W426B66
Record Status Validated (UNII)
Record Version
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Name Type Language
G-749
Common Name English
Code System Code Type Description
FDA UNII
B06W426B66
Created by admin on Sat Jun 26 02:56:47 UTC 2021 , Edited by admin on Sat Jun 26 02:56:47 UTC 2021
PRIMARY
CAS
1457983-28-6
Created by admin on Sat Jun 26 02:56:47 UTC 2021 , Edited by admin on Sat Jun 26 02:56:47 UTC 2021
PRIMARY
PUBCHEM
78357765
Created by admin on Sat Jun 26 02:56:47 UTC 2021 , Edited by admin on Sat Jun 26 02:56:47 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY