Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, Gentaur another in time delivery

Pubmed ID :25896848
Publication Date : //

Targeting of FLT3-ITD kinase contributes to high selectivity of imidazoacridinone C-1311 against FLT3-activated leukemia cells.


Drugs targeting receptor tyrosine kinase FLT3 are of particular interest since activating FLT3-internal tandem duplication (ITD) mutations abundantly occur in fatal acute myeloid leukemias (AMLs). Imidazoacridinone C-1311, a DNA-reactive inhibitor of topoisomerase II, has been previously shown to be a potent and selective inhibitor of recombinant FLT3. Here, we expand those findings by studying its effect on leukemia cells with wild-type FLT3, FLT3-ITD mutant and no FLT3 receptor. While brief C-1311 exposure blocked wild-type and FLT3-ITD activity, profound and sustained inhibition was achieved only for FLT3-ITD mutants. C-1311 inhibited FLT3 downstream pathways (MAPK and AKT) independent of FLT3 status, yet translation to decreased viability was significant in FLT3-ITD cells. RNA interference against FLT3-ITD reduced cytotoxic effect and apoptosis induced by C-1311, indicating selective inhibition of FLT3-ITD crucial for high efficacy of drug against activated leukemia cells. Cellular responses in treated FLT3-ITD mutants included G1 and G2/M phase arrest, moderate inhibition of Bcl-2, caspase-3 activation, PARP cleavage, and depolarization of mitochondria. Consistent with selective decrease in FLT3-ITD activity, C-1311 remarkably reduced antiapoptotic survivin mRNA and protein expression, correlating well with enhanced apoptosis of FLT3-ITD cells. No survivin decrease and respectively lower level of apoptosis was found in wild-type and null-FLT3 cells. Combination of C-1311 with cytarabine or doxorubicin again showed distinct synergistic activity in FLT3-ITD-positive cells. The ability of C-1311 to selectively target constitutively active FLT3, suggests a favorable therapeutic index for AML carrying FLT3-ITD mutations. Thus further preclinical and clinical studies addressing its potency against FLT3-ITD kinase is well justified.

Authors : Skwarska Anna , Augustin Ewa , Beffinger Michał , Wojtczyk Anita , Konicz Sonia , Laskowska Katarzyna , Polewska Joanna ,

Related products :

Catalog number Product name Quantity
orb80326 Human Flt3-Ligand Sf9 protein Flt3-Ligand Human Recombinant produced in Sf9 insect cells is glycosylated, polypeptide chain containing 155 amino acids and having migrating on SDS-PAGE at 19kDa. Flt3-L 2
orb82611 Rhesus macaque Flt3 Ligand protein Flt3 ligand (FL) is a recently identified hematopoietic cytokine whose activities are mediated by binding to the transmembrane glycoprotein Flt3. Flt3 was first disc 2
PK-FLT3-A010 Kinases: FLT3, protein, Expression system: Sf9 cells 10
18-272-195184 Flt3 ligand - Goat polyclonal to Flt3 ligand; EC 2.7.10.1; Tyrosine-protein kinase receptor FLT3; Stem cell tyrosine kinase 1; STK-1; CD135 antigen Polyclonal 0.025 mg
18-272-195182 Flt3 ligand - Goat polyclonal to Flt3 ligand; EC 2.7.10.1; Tyrosine-protein kinase receptor FLT3; Stem cell tyrosine kinase 1; STK-1; CD135 antigen Polyclonal 0.025 mg
orb84803 FLT3L protein Flt3 ligand (FL) is a recently identified hematopoietic cytokine whose activities are mediated by binding to the transmembrane glycoprotein Flt3. Flt3 was first discovered as a member of 10
E0039m ELISA Kit FOR Receptor-type tyrosine-protein kinase FLT3; organism: Mouse; gene name: Flt3 96T
DL-Flt3-Hu Human FMS Like Tyrosine Kinase 3 (Flt3) ELISA Kit 96T
E0039h ELISA kit CD135,Fetal liver kinase-2,FL cytokine receptor,FLK2,FLK-2,FLT3,FLT-3,Fms-like tyrosine kinase 3,Homo sapiens,Human,Receptor-type tyrosine-protein kinase FLT3,Stem cell tyrosine kinase 1,ST 96T
E0039h ELISA CD135,Fetal liver kinase-2,FL cytokine receptor,FLK2,FLK-2,FLT3,FLT-3,Fms-like tyrosine kinase 3,Homo sapiens,Human,Receptor-type tyrosine-protein kinase FLT3,Stem cell tyrosine kinase 1,STK1,ST 96T
U0039h CLIA CD135,Fetal liver kinase-2,FL cytokine receptor,FLK2,FLK-2,FLT3,FLT-3,Fms-like tyrosine kinase 3,Homo sapiens,Human,Receptor-type tyrosine-protein kinase FLT3,Stem cell tyrosine kinase 1,STK1,STK 96T
18-783-75516 RABBIT ANTI HUMAN CD135 - FLT3; EC 2.7.10.1; Tyrosine-protein kinase receptor FLT3; Stem cell tyrosine kinase 1; STK-1; CD135 antigen Polyclonal 0.05 mg
E0039m ELISA kit Fetal liver kinase 2,FL cytokine receptor,FLK-2,Flk-2,Flt3,FLT-3,Flt-3,Fms-like tyrosine kinase 3,Mouse,Mus musculus,Receptor-type tyrosine-protein kinase FLT3,Tyrosine-protein kinase recep 96T
orb80324 Human Flt3-Ligand HEK protein Flt3-Ligand Human Recombinant produced in HEK293 cells is glycosylated, polypeptide chain, migrates as diffuse band on SDS-PAGE due to heterogeneous glycosylation at 30kD 2
18-783-78399 RABBIT ANTI HUMAN Flt3 LIGAND Biotin - Fms-related tyrosine kinase 3 ligand; Flt3 ligand; Flt3L Polyclonal 0.05 mg
18-783-78398 RABBIT ANTI HUMAN Flt3 LIGAND - Fms-related tyrosine kinase 3 ligand; Flt3 ligand; Flt3L Polyclonal 0.1 mg
orb80325 Mouse Flt3-Ligand protein Flt3-Ligand Mouse Recombinant produced in E.coli is non-glycosylated, polypeptide chain containing 144 amino acids and having a molecular mass of 16431 Dalton. Flt3-Ligand is 2
orb80029 Human Flt3-Ligand protein Flt3-Ligand Human Recombinant produced in E.coli is non-glycosylated, polypeptide chain containing 155 amino acids and having a molecular mass of 17605 Dalton. Flt3-Ligand is 2
10-663-45236 Flt3-Ligand glycosylated Human - Fms-related tyrosine kinase 3 ligand; Flt3 ligand; Flt3L N_A 0.002 mg
10-663-45236 Flt3-Ligand glycosylated Human - Fms-related tyrosine kinase 3 ligand; Flt3 ligand; Flt3L N_A 0.01 mg
10-663-45236 Flt3-Ligand glycosylated Human - Fms-related tyrosine kinase 3 ligand; Flt3 ligand; Flt3L N_A 1 mg
E0039m ELISA Fetal liver kinase 2,FL cytokine receptor,FLK-2,Flk-2,Flt3,FLT-3,Flt-3,Fms-like tyrosine kinase 3,Mouse,Mus musculus,Receptor-type tyrosine-protein kinase FLT3,Tyrosine-protein kinase receptor f 96T
U0039m CLIA Fetal liver kinase 2,FL cytokine receptor,FLK-2,Flk-2,Flt3,FLT-3,Flt-3,Fms-like tyrosine kinase 3,Mouse,Mus musculus,Receptor-type tyrosine-protein kinase FLT3,Tyrosine-protein kinase receptor fl 96T
10-663-45164 FLT3-Ligand Human - Fms-related tyrosine kinase 3 ligand; Flt3 ligand; Flt3L N_A 0.002 mg
10-663-45172 FLT3-Ligand Murine - Fms-related tyrosine kinase 3 ligand; Flt3 ligand; Flt3L N_A 0.002 mg


https://antibody-antibodies.com/ | https://gentaur.com/ | https://gen-script.com/ | https://diagenox.com/ | https://clonagen.com/ | http://gentaursearch.com/ | http://gentaurpub.com/ | https://gentaur-online.com/ | http://anti-anti-pdf.com/ | http://gentaur-worldwide.com/

 

Gentaur Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
[email protected] | Gentaur | Gentaur





Gentaur Ltd.
Unicorn House, Station Cl
Hertfordshire, Potters Bar EN6 1TL
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
[email protected] | Gentaur | Gentaur

 

 




Gentaur France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017
RIB 30004 00187 00010092253 10
BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG
IBAN FR76 3000 4001 8700 0100 9225 310
[email protected] | Gentaur | Gentaur

Gentaur GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: +49 0241 40 08 90 86, +49 0241 95 78 94 78, +49 0241 40 08 90 86
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
[email protected] | Gentaur | Gentaur

Gentaur U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
[email protected]

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




Gentaur Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
[email protected] | Gentaur | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






Gentaur Spain
tel:0911876558
[email protected] | Gentaur | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: [email protected] | Gentaur | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

Gentaur Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

[email protected] | Gentaur | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

Gentaur Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
[email protected] | Gentaur | Gentaur